TRIUMPH Program Faculty Mentors

Dr. Allison received his Ph.D. from the University of Texas at Austin (Austin, TX) and completed a postdoctoral fellowship at Scripps Clinical and Research Foundation in the Department of Molecular Immunology (La Jolla, CA).  Dr. James Allison is the Chair of the Department of Immunology, the Vivian L. Smith Distinguished Chair in Immunology, Director of the Parker Institute for Cancer Research, and the Executive Director of the Immunotherapy Platform at MD Anderson Cancer Center. He has spent a distinguished career studying the regulation of T cell responses and developing strategies for cancer immunotherapy. Among his most notable discoveries are the determination of the T cell receptor structure and that CD28 is the major costimulatory molecule that allows full activation of naïve T cells and prevents anergy in T cell clones. His lab resolved a major controversy by demonstrating that CTLA-4 inhibits T-cell activation by opposing CD28-mediated costimulation and that blockade of CTLA-4 could enhance T cell responses, leading to tumor rejection in animal models. This finding paved the wave for the emerging field of immune checkpoint blockade therapy for cancer. Work in his lab led to the development of ipilimumab, an antibody to human CTLA-4 and the first immune checkpoint blockade therapy approved by the FDA. Dr. Allison is one of the world’s most renowned scientists. Among many honors, he is a member of the National Academies of Science and Medicine and received the Lasker-Debakey Clinical Medical Research award in 2015. His current work seeks to improve immune checkpoint blockade therapies currently used by our clinicians and identify new targets to unleash the immune system in order to eradicate cancer.

Allison Laboratory Research:
The Allison laboratory is interested in murine models of tumor immunotherapy, T-cell activation and regulation, and the development of immunotherapy strategies for cancer.

Dr. Andreeff  received his M.D. and Ph.D. degrees at the University of Heidelberg, Germany, and additional training and faculty appointments  at the Memorial Sloan-Kettering Cancer Center (MSKCC) in New York, NY, in the Departments of Pathology and Leukemia. 

Dr. Andreeff has been a pioneer in flow cytometry since 1971, when he established the first flow cytometry laboratory at the University of Heidelberg, and  organized the first European conference on flow cytometry. In 1977 he joined Memorial Sloan-Kettering Cancer Center in New York, NY, became head of the Leukemia Cell Biology and Hematopathology flow cytometry laboratory, organized the first Clinical Cytometry Conference in 1986 and the first Molecular Cytogenetics Conference in 1990.

 He is professor of medicine and holds the Paul and Mary Haas Chair in Genetics at MD Anderson. He has received uninterrupted NCI funding for over 30 years, serves as PI of the P01 grant entitled “The Therapy of AML”, participates as PI in MD Anderson Leukemia, Lymphoma, Ovarian and Breast Cancer SPORE grants, the CML P01 and additional R21 and R01 grants. He has published over 450 peer-reviewed papers, 5 books and 75 book chapters.

Andreeff Laboratory Research:
Molecular Hematology and Therapy is a Section in the Leukemia Department with close links to the Department of Stem Cell Transplantation and Cellular Therapy. Our focus is on leukemia research, with emphasis on apoptosis regulation, signaling pathways (FLT3-Ras-Ras-MEK-ERK, PI3K-AKT-mTOR, STAT3 and 5) , their links to apoptosis and autophagy and to the micro-environment. The Section encompasses 12 faculty and 25 additional scientists and includes the MD Anderson CCSG-sponsored "Flow Cytometry/Cell Sorting/Confocal Microscopy" Core Lab. Investigations of apoptosis and cell signaling pathways resulted in the development of new drug targets including Bcl-2, BclXL, McL-1, MDM2/p53, inhibitors-of-apoptosis proteins (XIAP, Survivin, cIAP1,2), FLT3-ITD, AKT/mTOR and pERK, which we have moved from basic to translational research into trials. We emphasize that successful drug development has to target the right cells ("primary stem cells", not cell line cells) in the physiological, i.e. hypoxic tumor microenvironment. Our group has major expertise in the study of hematopoietic and solid tumor systems . We were first to report the critical role of bone marrow-derived MSC (mesenchymal stem cells) in the formation of tumor stroma and have developed therapies that deliver therapeutic genes into tumors by way of MSC. Several transgenic and knock-out mouse models have been developed to provide a better understanding of tumor- and microenvironmental molecular biology. Leukemia cells with most relevant translocations and mutations have been generated in collaboration with CSH. Major efforts are ongoing to disrupt interactions between leukemia/tumor stem cells and their micro-environment (targeting CXCR4, VLA-4, CD44). The first fully human system forming bone and bone marrow has been developed in immuno-deficient NOG mice, whose components can be genetically modified. Finally, in collaborations with pharmaceutical corporations and biotechnology companies, drugs are being developed targeting genes, RNAs and proteins of interest.

Dr. Bast received his M.D. at Harvard Medical School (Boston, MA) and completed postgraduate training  and research at several notable institutions including Massachusetts General Hospital, Johns Hopkins Hospital, the National Cancer Institute, Harvard Medical School, Peter Bent Brigham Hospital, and Sydney Farber Cancer Institute. He is the recipient of numerous recognitions and awards.

Bast Laboratory Research:
Our laboratory is addressing three of the critical problems in the management of ovarian cancer, including late detection, drug resistance and tumor dormancy, while attempting to understand the heterogeneity of ovarian cancers at a cellular and molecular level. Projects in which fellows would be welcomed include:

1) Function of imprinted tumor suppressor genes that are downregulated in ovarian cancer. Over the last decade, we have identified several imprinted tumor suppressor genes whose expression is decreased or lost in ovarian cancer. Among these, we have best characterized ARHI (DIRAS3) which encodes a 26kD GTPase with 50% homology to Ras, but with an opposite function that can be attributed to a 34 amino acid N terminal extension. ARHI is downregulated in 60% of ovarian cancers associated with decreased disease free survival. Expression from the single functioning allele can be inhibited by LOH, hypermethylation or transcriptional regulation by E2F1 or E2F4 in different cancers. Re-expression of ARHI inhibits proliferation and motility while inducing autophagy and tumor dormancy. Current studies, funded by an R01, concern mechanisms underlying ARHI-induced autophagy and requirements for survival of dormant ovarian cancer cells. For these studies, we have developed the first inducible model for tumor dormancy in ovarian cancer.

2) Individualized enhancement of primary sensitivity to paclitaxel in different ovarian cancers. Through a high throughput kinome siRNA screen, my laboratory has identified more than 30 kinases that regulate paclitaxel sensitivity in ovarian cancer cell lines by modulating centrosome function (SIK2), paclitaxel retention (CDK5) or microtubule stability (ILK, FER). Both fundamental studies of mechanism and translational studies of siRNA therapy in combination with paclitaxel are being pursued.   

3) Identification of biomarkers and strategies for early detection of ovarian cancer. Having developed the CA125 serum assay for monitoring ovarian cancer, we have tested some 115 potential biomarkers to identify four biomarker panels for early stage disease. Currently, we are testing several such panels for their ability to discriminate women with pre-clinical and early stage disease from healthy women. Supported by an Ovarian SPORE, a multi-year screening trial is being conducted in 3000 apparently healthy postmenopausal women to evaluate the specificity and positive predictive value of ultrasound in a small fraction of women with rising levels of biomarkers from year to year. To date, the trial has prompted 8 operations to discover 5 cases of ovarian cancer, all in early stage, consistent with a positive predictive value of 37%, i.e. only 3 operations per case of ovarian cancer detected. To facilitate these studies, we are collaborating with investigators at Rice to place assays on nanobiochips for testing at point of service. Recent work with protein expression arrays has identified a panel of 115 auto antibodies which promise to detect pre-clinical disease in a larger fraction of women. 

Dr. Byers completed her B.A. degree in Molecular Biology at Princeton University in 1998, her M.D. degree at Baylor College of Medicine in 2003, and M.S. degree in Patient-Based Research at the University of Texas Graduate School of Biomedical Sciences in 2009. Following her Clinical Residency in Internal Medicine at Johns Hopkins, Dr. Byers joined MD Anderson Cancer Center in 2006 as a Clinical Fellow in Medical Oncology and later as an Advanced Scholar Fellow. During her fellowship, Dr. Byers focused on studying gene and protein profiles of tumor samples obtained from lung cancer patients. Her work revealed major differences in the cellular pathways in small cell lung cancer (SCLC) as compared to non-small cell lung cancer (NSCLC), leading to the identification of the protein PARP1 as a novel therapeutic target for small cell lung cancer. In 2010, Dr. Byers was appointed as an Assistant Professor in the Department of Thoracic/Head and Neck Medical Oncology, and was subsequently promoted to Associate Professor in 2017. She has an impressive list of funded grants and awards, including Women Leading the Way and NCI Cancer Clinical Investigator Team Leadership Award (both in 2013), R. Lee Clark Fellow Award and President’s Recognition for Faculty Excellence (both in 2014), ASCO Top Ten Clinical Research Achievement Award (2015), and an NIH R01 (2016). 

Byers Laboratory Research: 
Research in the Byers Laboratory is dedicated to understanding the causes of resistance to treatment in patients diagnosed with thoracic cancers and identifying novel therapeutic targets for these diseases. The lab employs high-throughput profiling techniques to identify candidate predictive biomarkers and potential new therapeutic targets in lung cancers. Specific markers of interest which are being further investigated as therapeutic targets include the DNA damage response (DDR)proteins PARP1, WEE1, and CHK1 in small cell lung cancer and the tyrosine kinase receptor Axl in non-small cell lung cancer. Previously, they demonstrated that the Axl is a marker that can predict which patients will be resistant to treatment with EGFR inhibitors, a discovery that led to Dr. Byers initiating a clinical trial using new drug combinations to target Axl in patients resistant to therapies involving EGFR inhibitors. In addition, Dr. Byers is currently leading several clinical trials testing DDR inhibitors alone and in combination with chemotherapy for patients with recurrent small cell lung cancer. 

George A. Calin received both his M.D. and Ph.D. degrees at Carol Davila University of Medicine in Bucharest, Romania. After working cytogenetics as undergraduate student with Dr. Dragos Stefanescu in Bucharest, he completed a cancer genomics training in Dr. Massimo Negrini’s laboratory at University of Ferrara, Italy. In 2000 he became a postdoctoral fellow at Kimmel Cancer Center in Philadelphia, PA. Here, he worked in Dr. Carlo Croce's laboratory and was the first to discover the link between microRNAs and human cancers, a finding considered as a milestone in microRNA research history. He is presently a Professor in Experimental Therapeutics and Leukemia Departments at MD Anderson Cancer Center in Houston and studies the roles of microRNAs and other non-coding RNAs in cancer initiation and progression and in immune disorders, as well as the mechanisms of cancer predisposition linked to non-coding RNAs. Furthermore, he explores the roles of body fluids miRNAs as potential hormones and biomarkers, as well as new RNA therapeutic options for cancer patients. Simply, he is having fun making discoveries and publishing and, from time to time, getting funded grants!

Calin Laboratory Research:
My long-term goal is to establish the roles of non-coding RNAs in human diseases. My main research interests are: 1) the involvement of non-coding RNAs in human diseases in general and of microRNAs in human cancers in particular, 2) the study of familial predisposition to human cancers, 3) the identification of ncRNA biomarkers in body fluids, and 4) the development of new RNA-based therapeutic options for cancer patients. Current areas of research in my laboratory are: 

1) Identification of the Roles of microRNAs and Other Non-Coding RNAs in Cancer PredispositionFamilial cancers represent diseases in which non-coding RNAs have central pathogenetic roles. We hypothesize that previously non-identified, non-coding RNAs with roles in sporadic and familial cancers could be identified by using their genomic association (flagging) with known cancer-associated, single-nucleotide polymorphisms (SNPs). Furthermore, SNPs in interactor sites with microRNAs are involved in cancer predisposition. The genome-wide identification of non-coding RNAs predisposed to cancer would prove a new mechanism of cancer predisposition with clear implications for further molecular screening and diagnosis.

2) Identification of Non-Coding RNAs Involved in Metastasis During tumorigenesis, genome-wide abnormalities in both microRNAs and ultra-conserved genes (UCGs) occur in a correlated way that results in our hypothesis that dramatic differences occur in the expression of UCGs and miRNAs in non-metastatic versus metastatic cancers. microRNAs have important genes as targets – including known oncogenes and tumor suppressors involved in pancreatic invasion and metastasis. Additionally, miRNAs interact directly with and regulate the expression of UCGs and/or, conversely, UCGs can regulate the expression of miRNAs. The transcriptional or post-transcriptional down-regulation of target levels by miRNAs and UCGs may have functional consequences by impairing the cell cycle and the survival, migration and invasion capacity of cancer cells.

3) Identification of microRNAs and Other Non-Coding RNAs as Diagnostic and Prognostic Markers in Human Cancers microRNAs as the Oldest Hormones MicroRNA levels in the plasma from cancer patients are significantly different than those of non-cancer control individuals. The plasma miRNAs levels from cancer patients correlate with clinical and prognostic parameters and the miRNA quantification from plasma could be included as a new prognostic marker. Furthermore, the identification of traces of specific miRNAs, known to have a pathogenetic effect, could signal the recurrence of disease. Human-specific ncRNAs exist in the genome and are involved in the functional fingerprints that differentiate human cancers from cancers in other organisms. microRNAs are secreted by malignant cells in the microenvironment and uptake directly or through bodily fluids by effector cells.

4) Development of New Therapeutic Strategies Involving microRNAs and Other Non-Coding RNAs

Dr. Junjie Chen earned his Ph.D. in Cell and Molecular Biology from the University of Vermont. His Postdoctoral Fellowships at Harvard Medical School focused on tumor suppressor P53, the cell cycle regulatory p21, and breast cancer susceptibility genes BRCA1, BRCA2 and control of DNA replication and repair. Dr. Chen has since held faculty positions at Mayo Foundation, Mayo Clinic College of Medicine, and the Yale University School of Medicine. He has served as Professor and Chair of the Experimental Radiation Oncology Department at MD Anderson since 2009.

Chen Laboratory Research:                                                                                                                                                                                           
Our research focuses on the understanding of molecular mechanisms underlying genomic instability and tumorigenesis. Maintenance of genomic integrity following DNA damage requires the coordination of DNA repair with various cell-cycle checkpoints. The hope is that by elucidating these complex DNA damage-responsive pathways, we will reveal how deregulation of them contributes to tumor initiation and/or progression and how to take advantage of this deregulation in cancer therapy. We have been studying DNA damage signaling and DNA repair pathways since 1999. We have identified and performed in-depth functional studies of many key cell-cycle checkpoint and DNA repair proteins in several DNA damage signaling and repair pathways. Over the past few years, we expand our studies to include whole genome CRISPR/Cas9 screening and quantitative proteomics in order to achieve a comprehensive understanding of the network involved in DNA repair and determine how these proteins and pathways intersect, interact, communicate, coordinate, and collaborate for genome maintenance. In addition, we also successfully carried out genome-wide and network studies in several tumor suppressive and oncogenic pathways, including cyclin-dependent kinases, Hippo/YAP pathway, Wnt pathway, and more recently AMPK and energy stress pathway. We are combining our ability to conduct network analysis with our expertise in performing detailed mechanistic studies to establish physical and functional networks of DNA repair and other cancer-related pathways, which will facilitate our ability to exploit these pathways for cancer therapy

Dr. Chen graduated from Tsinghua University, China, received Ph.D. from University of Illinois at Urbana-Champaign (UIUC) in Electrical and Computer Engineering (ECE), and postdoctoral training from University of California at San Diego in Biochemistry and Biophysics. From 2005 to 2011, he worked for Washington University School of Medicine in St. Louis as a research faculty on cancer genomics.

Dr. Chen has designed, developed, and co-developed a set of computational tools such as BreakDancer (Nature Methods, 2009) and VarScan (Bioinformatics 2009), which have been widely used in human genetics and cancer genomics and led to discovery of cancer genes such as IDH1 (NEJM, 2009) and DNMT3A (NEJM, 2010) in AML.  He has been one of the key developers and data scientists in the Cancer Genome Atlas (TCGA) and the 1000 Genomes Project (Nature 2011).  Since joining MD Anderson in 2011, he has been the Director of Bioinformatics for the Institute of Personalized Therapy (IPCT), which applies bioinformatics analysis for timely, accurate diagnosis and personalized therapy. He recently focuses on developing artificial-intelligence and systems-biological approaches to construct and integrate the multiomics of cancer cell populations towards understanding the heterogeneity and the evolution of cancer and identifying targets that are useful for diagnosis and treatment. 

Ken Chen Lab (KClab) Research:                                                                                                                                                                               
KClab at MDACC focuses on developing computational approaches for characterizing and interpreting heterogeneous tumor specimens and clinical data towards identifying molecular targets and biomarkers that are useful for personalized diagnosis and medicine. Recently, trainees in the lab have developed a series of methods such as Monovar (Nature Methods, 2016), SiFit (Genome Research, 2017), Cyclum (Nature Communications, 2020), and SCMER (Nature Computational Science, 2021) for single-cell variant calling, cell type/state classification, gene signature inference and developmental trajectory/lineage construction from single-cell DNA, RNA, ATAC sequencing as well as CyTOF data. 

Dr. DePinho received his M.D. at Albert Einstein College of Medicine. He completed postdoctoral fellowships at Albert Einstein College of Medicine in the departments of Cell Biology and Biochemistry & Biophysics. 

DePinho Laboratory Research:
Our basic and translational research program focuses on pathways and processes governing aging and age-related disorders, particularly cancer.  Our experimental approach is built upon the use of unbiased computational analyses of multi-dimensional datasets, genetically engineered mouse models, and human-mouse comparisons on the molecular, cellular and physiological levels.  Through MD Anderson’s Institute for Applied Cancer Science, we strive to drive basic discoveries to therapeutic and diagnostic endpoints in a systematic action-oriented culture. Our activities have focused on (i) defining the role of telomeres in governing cancer genome alterations, epithelial carcinogenesis, aging and degenerative disorder (both acquired and inherited), (ii) utilizing genetically engineered mouse (GEM) models to study human cancers with an emphasis on comparative oncogenomics and proteomics to discover and ultimately validate new genes for enlistment into drug discovery, early detection or prognostic biomarkers; there is a focus on glioma, pancreatic cancer, colorectal cancer and prostate cancer, and (iii) elucidating pathways orchestrating aging and age-related disorders with the goal of therapeutically manipulating such pathways to attenuate the incidence of age-associated diseases such as cancer, cardiomyopathy and neurodegeneration.  Our mission is to convert basic knowledge into clinical endpoints that will impact on patient outcomes in meaningful ways. 

Giulio Draetta trained as a physician at the University of Naples Medical School, Italy. He then pursued a postgraduate degree in Biochemistry and performed postdoctoral research at the National Cancer Institute in Bethesda and at the Cold Spring Harbor Laboratory, New York. Subsequently, he became an investigator at the Cold Spring Harbor Laboratory and then at the European Molecular Biology Laboratory, Heidelberg, Germany. In 1992, he returned to the USA to establish Mitotix, a biotechnology company focused on drug discovery in the areas of cancer, immunosuppression and infectious diseases. Dr. Draetta then returned to academia as a founding member of the Department of Experimental Oncology of the European Institute of Oncology in Milan, Italy. While in Italy, he held a joint appointment with Pharmacia Oncology where he managing the Oncology portfolio, which resulted in several IND approvals including SU11248 (Sutent®), as well as Aurora and Cdk small molecule inhibitors. In 2004, Dr. Draetta joined Merck Research Laboratories, as Executive Director and Head of Oncology Research in Boston. In 2007, he was promoted to Vice President and World Wide Basic Franchise Head, Oncology. In 2008, Dr. Draetta was appointed Dana Farber Presidential Scholar and Deputy Director of the Belfer Institute for Applied Cancer Science at Dana Farber Cancer Institute. Dr. Draetta was also Chief Research Business Development Officer at Dana Farber Cancer Institute. Since September 2011, Dr. Draetta has served as the director of the newly established Institute for Applied Cancer Science (IACS) and is a professor in the Department of Genomic Medicine.

Draetta Laboratory Research:
The focus of our research is to identify genetic elements that are required for tumor maintenance in glioblastoma, triple-negative breast cancer, and pancreatic cancer.  Patients with these aggressive, lethal cancers currently have few effective therapeutic options; therefore, an in-depth understanding of the signaling mechanisms in these cancers is needed to allow the rational development of effective targeted therapies.  In collaboration with the Institute for Applied Cancer Science, our lab has developed a functional genomics screening platform wherein lineage, genetic, and microenvironmental influences are carefully controlled to identify context-specific molecular targets.  This novel approach allows us to rapidly identify specific genetic elements that drive or suppress tumor latency.  Upon validation of targets, our lab can leverage ready access to patient samples and cutting-edge technology to rapidly translate research discoveries into improved patient care. Our early screening efforts have resulted in several on-going projects, including projects in cancer cell metabolism and epigenetics.

Dr. Goswami received her medical degree from Gauhati Medical College before pursuing her Ph.D. in Immuology at Baylor College of Medicine. Dr. Goswami then went on to complete a clinical residency in internal medicine at The University of Pittsburgh Medical Center before joining MD Anderson in 2013. Dr. Goswami currently serves as an Assistant Professor in the Departments of Genitourinary Medical Oncology and Immunology.

Goswami Laboratory Research:
Based on understanding the mechanisms of epigenetic regulation and its impact on the tumor microenvironment and immune cell subsets, our goal is to create approaches to target specific pathways to overcome resistance to immune-based therapies. We utilize reverse translational studies to identify predictive biomarkers in patients for response to immune checkpoint therapy, and develop pre-clinical models alongside high throughput single-cell technologies to identify pathways of response and resistance.

Throughout her career, Dr. Guise has made seminal contributions to our understanding of cancer effects on the musculoskeletal system, beginning with demonstrating the central role for tumor–secreted PTHrP, and its downstream mediator, RANKL, in osteolytic bone metastases. These studies were the first to provide the rationale for RANKL antibodies to treat bone metastases, now FDA approved for all solid tumor metastases to bone and multiple myeloma. She developed the first animal models of osteoblastic metastases that defined the causal role of endothelin-1, and described the role of bone-derived TGF Beta in promoting bone metastases of multiple solid tumors. She showed that bone microenvironment hypoxia enhanced TGF Beta signaling to promote bone metastases and identified an inhibitor of TGF Beta signaling, PMEPA1, which is regulated in prostate cancer and whose expression predicts metastases-free survival. Recently, she has shown that bone-derived TGF Beta induces oxidation of the skeletal muscle intracellular calcium release channel (ryanodine receptor) causing calcium leak & muscle weakness.     

Collectively, Dr. Guise has defined the role of tumor-bone cell interactions in the bone microenvironment and the resultant systemic effects on the musculoskeletal system that have profound implications for the treatment of bone metastases and its associated muscle weakness. Dr. Guise has received multiple honors and awards in recognition of her contributions to bone research: Outstanding Investigator Award, International Bone & Calcium Institute; Fuller Albright Award, American Society Bone & Mineral Research; Komen Scholar, Susan Komen Foundation; & Paula Stern Achievement Award, American Society Bone & Mineral Research. Her recruitment will bolster our efforts to advance research and treatment of musculoskeletal complications of malignancy.

Dr. Heymach earned his M.D. and his Ph.D. in Neuroscience from Stanford University. He completed a Clinical Internship and Residency in Internal Medicine at Brigham and Women’s Hospital in Boston, MA followed by a Clinical Fellowship in Medical Oncology at Dana-Farber/Partners Cancer Care Medical Oncology Fellowship Program. He is a board certified Medical Oncologist and Internal Medicine physician. Dr. Heymach is a Professor in the Cancer Biology department and serves as Chair of the Thoracic/Head and Neck Medical Oncology Department at MD Anderson. He holds the David Bruton, Jr. Chair in Cancer Research, he is a Co-Leader of the MD Anderson Lung Cancer Moon Shot Program, and directs a prolific translational cancer research laboratory at MD Anderson Cancer Center.

Dr. Heymach’s Research Laboratory:
The mission of Dr. Heymach’s laboratory is to improve the clinical outcome of lung and head and neck cancer patients through scientific advances in understanding the molecular drivers of the disease, the development of predictive biomarkers of drug sensitivity, and the identification of new therapies and mechanisms of resistance. Dr. Heymach’s research has both basic and translational components and employs integrative approaches of genomic and proteomic analyses of human samples coupled with an extensive collection of cell lines and mouse models to advance the understanding of lung cancer and head and neck malignancies. Dr. Heymach’s laboratory interests include investigating new approaches for targetable pathways in EGFR, KRAS, and STK11/LKB1 mutant NSCLC, small cell lung cancer (SCLC), and other solid tumors, and mechanisms of resistance to immunotherapy in lung cancer.In addition, his laboratory has considerable broad expertize in the development of blood-based markers and in the testing of angiogenesis inhibitors in lung cancer and other solid tumors. The studies conducted in Dr. Heymach’s laboratory have a bench to bedside approach as preclinical studies can be validated through connections with vast clinical datasets, and promising findings can be rapidly translated into the clinic. His research efforts are focused on the following areas: 

1. Investigating new targetable pathways and mechanisms of therapeutic resistance in EGFR mutant NSCLC including:

- Therapeutic targeting of subgroups of EGFR and HER2 mutant NSCLC (e.g. exon 20 and exon 18 EGFR mutations). Recently, Dr. Heymach’s laboratory identified a novel therapy for tumors bearing EGFR and HER exon 20 mutations that have remained refractory to all standard therapies. Through in vitro and in vivos creens, coupled with molecular modeling, they identified a highly  active drug, poziotinib that had previously been tested for standard EGFR mutations and was discontinued (Robichaux et al. Nature Med 2018). Based on this preclinical data a phase II trial of poziotinib is being conducted in MD Anderson and initial results indicate high anti-tumor activity with best objective response of PR (partial response) in 55% of 44 evaluable patients. His laboratory efforts are currently focused on identifying resistance mechanisms to poziotinib as well as investigating new treatment strategies for exon 18 EGFR and HER2 mutant NSCLC, including new TKIs and immunotherapy.

- Investigating EMT and other mechanisms of tyrosine-kinase inhibition (TKI) resistance and immunosuppression in EGFR mutant NSCLC. Dr. Heymach’s laboratory has made several fundamental advances in elucidating mechanisms of resistance to EGFR TKIs and developing new strategies to overcome this resistance in EGFR-mutant lung cancer. His laboratory identified key pathways driving invasiveness and EGFR inhibitor resistance, including an EGFR/HIF/MET axis; the VEGF/KDR pathway and epithelial-to-mesenchymal transition (EMT). His laboratory also identified chronic stress hormones as drivers of EGFR inhibitor resistance through beta-2 adrenergic receptors (Nilsson et al. Science Trans Med 2017). This resistance can be blocked by beta-blockers and based on this study, a randomized trial using the beta-blocker propranolol is in development. His laboratory has also a focus on investigating the molecular determinants of immunologically inert tumors like EGFR or LKB1 mutant NSCLC, and to test innovative approaches for enhancing antitumor immunity like CART-cell therapies, NK-cell therapies, drug-conjugated antibodies and novel therapeutic combination approaches.

- Investigating new approaches for targeting drug-resistant persister cells in EGFR mutant NSCLC. Tumor cells (EGFR mutant cells) that are not killed by initial treatment with TKIs -termed persister cells- can be present in the residual tumor and may remain quiescent or clinically invisible for prolonged periods of time to eventually progress to become drug resistant cells. Dr. Heymach’s laboratory is currently involved in the study of these drug-resistant persister cell population through innovative techniques (single-cell RNA/DNA sequencing) and mouse models to find new effective targeting approaches in early stage EGFR mutant NSCLC.

2. Investigating novel immunotherapy approaches for lung cancer, including:

- Studying genomic determinants of response to immunotherapy in NSCLC. Dr. Heymach’s laboratory and collaborators  identified that co-occurring  genomic alterations in three tumor suppressors (P53, LKB1, and CDKN2A) are critical drivers of this heterogeneity and define subsets of KRAS-mutant NSCLC that have distinct biology, immune profiles, and therapeutic vulnerabilities (Skoulidis et al. Can Disc 2015). His laboratory, working in collaboration with a multi-institutional team of clinical investigators,   investigated the genomic determinants of  response to immunotherapy and recently identified mutations in LKB1 as  the strongest predictor of immunotherapy resistance in lung adenocarcinoma (Skoulidis et al. Can Disc 2018).  Dr. Heymach is the PI of an R01 grant investigating the mechanisms underlining these immune-inert tumors to develop precise immunotherapy approaches for enhancing antitumor immunity and overcoming resistance by using well-established preclinical NSCLC models. Examples of these approaches include the targeting of potential metabolic vulnerabilities of tumors, the restoration of antigen-presentation machinery, and the targeting of immunosuppression-related cytokines.

- Identifying new approaches to enhance immunotherapy in SCLC. New therapeutic strategies are desperately needed for SCLC. Dr. Heymach’s laboratory has elucidated the signaling “circuitry” of NSCLC and SCLC and identified PARP-1 and EZH2 as novel therapeutic targets for SCLC (Byers et al. Can Disc 2012). This has led to the development of two clinical trials of PARP inhibitors, which will be conducted in MD Anderson and other sites.  One particular understudied feature of SCLC is that it has a relatively immunosuppressed phenotype with relatively low levels of infiltrating T-cells and evidence of reduced antigen presentation. Recently, atezolizumab (anti-PD-L1) has been FDA-approved for its use in combination with chemotherapy in SCLC but further studies are needed to enhance the efficacy of these agents. To address this need, Dr. Heymach’s laboratory in conjunction with a multidisciplinary team, focus on the identification of new targets and the development of novel approaches for SCLC including CART-cell therapies, agents that protect immune cells from chemotherapy-induced toxicity, the targeting of epigenetic modulators, etc. 

3. Identification of blood-based biomarkers and mechanisms of resistance to angiogenesis inhibitors.
Dr. Heymach’s laboratory showed that  the  majority of  changes  associated with  therapeutic  resistance occur  in stromal  cells (including  endothelial  cells), rather  than  tumor cells  and  that targeting  these  stromal pathways including FGFR2, EGFR, and MET could delay the emergence of resistance (Cascone et al. J Clin Invest 2011; Xu et al. Oncogene 2010). These findings have impacted the clinical development  of  angiogenesis inhibitors  and  their biomarkers  as  they have  suggested  rational combination  regimens and  revealed  that biomarker  approaches  in this  area  must take  into  account not  only tumor  cells, but  also  stromal and  host  effects. His laboratory also  developed  CAF signatures  predicting  response in early stage NSCLC, head and neck, and metastatic renal cell carcinoma patients (Nikolinakos et al. Can Res 2010; Hanrahan et al. JCO 2010; Kopetz et al. JCO 2010; de Groot et al, CCR, 2011).  

4. Identification of new therapies and biomarkers for predicting drug response in head and neck cancer.
Dr. Heymach has also investigated new therapeutic targets, signaling pathways, and resistance mechanisms in head and neck cancers using  high-throughput  profiling. This includes the identification of an Axl/PI3K/PD-L1 axis as well as focal adhesion kinase (FAK) as drivers of  radioresistance in HNSCC (Skinner et al. Clin Can Res 2016 and 2017). His laboratory has also recently identified that NOTCH1 activating mutations identify a distinct subgroup with poor prognosis and a propensity to bone and liver metastasis (Ferrarotto et al. JCO 2017). Clinical trials based on all three of these findings are currently in progress or development; the trials targeting the NOTCH1 pathway in ACC could lead to the first targeted agent approval for this disease.  

5. The clinical testing of new therapies and treatment paradigms for lung cancer. Dr. Heymach’s laboratory conducted the first randomized trial of local consolidative therapy (LCT), consisting of surgery or radiotherapy, for oligometastatic NSCLC patients  with non-progressive disease after initial systemic treatment. The study showed a significant prolongation in progression free survival (12 months in the LCT arm vs 3.9 months for the standard systemic approach) and a delay in new metastases (Gomez et al. Lancet Onc 2016). This LCT approach has already changed the standard for a subset of lung cancer patients, and its use may broaden based on these ongoing studies. Currently, Dr. Heymach’s group is expanding this approach to incorporate immunotherapy (the LONESTAR study) and TKIs (the NORTHSTAR study). 

Dr. Hunt earned her M.D. at the University of Tennessee Center for the Health Sciences (Memphis, TN) and completed her residency at UCLA School of Medicine, where she also served as Chief Resident in General Surgery. Dr. Hunt also completed a fellowship in surgical oncology at The University of Texas MD Anderson Cancer Center.

Hunt Laboratory Research:                                                                                                                                                                                           
Our laboratory has developed a research program for identifying novel therapeutic strategies and prognostic markers based on alterations in G1/S and G2/M checkpoints in tumor cells focusing on solid tumors such as breast, sarcoma, pancreatic and lung cancers. We are currently involved in five primary areas of research, which fall into translational and basic research categories: 1)   Inhibition of LMW forms of cyclin E as a therapeutic target in combination therapy for triple negative breast cancer. 2)   Delineation of how the alteration of cyclin E, a G1 cyclin, could lead to the tumorigenic phenotype and determination of the oncogenic potential of the altered forms of cyclin E in breast cancer.  3)   Determination of the mechanism of action of intracellular elastase and its inhibitor elafin in tumorigenesis and subsequent metastasis. 4)   Examination of mechanisms of action and resistance to CDK4/6 inhibitors in ER positive breast cancer patients. 5)  Identification of novel treatment strategies, targeting the cell cycle, for soft-tissue sarcomas.

Raghu Kalluri was born in St. Louis, Missouri and received his B.S. in Chemistry and Genetics. He received his Ph.D. in Biochemistry and Molecular Biology from the University of Kansas Medical Center and his M.D. degree from Brown University Medical School. Dr. Kalluri was a postdoctoral fellow and a research associate at the University of Pennsylvania Medical School and performed research in areas of tissue injury/repair and regeneration. In 1997 Dr. Kalluri moved to Harvard Medical School as an Assistant Professor of Medicine and as a faculty based in the Department of Medicine at the Beth Israel Deaconess Medical Center. In 2000 he was named Associate Professor and the Director of the Center for Matrix Biology, and in 2006 this program became the Division of Matrix Biology and Dr. Kalluri was appointed the Chief of the Division and also appointed as Professor of Medicine at Harvard Medical School. He held appointments in the Department of Biological Chemistry and Molecular Pharmacology at HMS, Harvard MIT Division of Health Sciences and Technology, Harvard Stem Cell Institute, and was a research fellow of the HMS Peabody Society. In 2012 Dr. Kalluri moved to The University of Texas MD Anderson Cancer Center as Professor and Chairman of the Department of Cancer Biology and the Director of the Metastasis Research Center. Dr. Kalluri currently holds the RE Bob Smith Distinguished Chair of Cancer Research. Dr. Kalluri recently received the Jacob Henle Medal from the Georg-August University in Germany to honor his discoveries related to tissue damage and regeneration, and cancer biology. He is the recipient of several mentorship and teaching awards from the Beth Israel Deaconess Medical Center, Harvard Medical School and MD Anderson Cancer Center. He is the recipient of several research excellence awards for his work on tissue damage/regeneration and cancer progression. He is the fellow of American Society of Clinical Investigation and the American Association for the Advancement of Science. Dr. Kalluri has published over 300 peer-reviewed manuscripts. Dr. Kalluri has an h-index of 121 with 63,978 lifetime citations (since 2014, h-index: 78 and 35,000 citations). Dr. Kalluri is ranked in the top 0.01% (ranked 659) of about 6.8 million scientists (covering 22 scientific fields) in the world for citation impact (https://doi.org/10.1371/journal.pbio.3000384). Dr. Kalluri has trained 107 postdoctoral fellows, 15 graduate students, and 63 undergraduate students, and 58 of his trainees hold academic positions around the world. At MD Anderson Dr. Kalluri teaches 1st year core courses for graduate students and medical students. He serves on science and health advisory panels in the USA and European Union, and on the editorial boards of several academic journals representing biology and medicine. Dr. Kalluri is a consulting editor of the Journal of Clinical Investigation and is the Deputy Editor of Cancer Research. Dr. Kalluri’s research had led to seminal discoveries in the area of tissue injury/regeneration, exosomes biology, cancer biology, and cancer metastasis. Dr. Kalluri’s work has resulted in several issued patents. Dr. Kalluri serves as an advisor to several biotechnology and pharmaceutical companies, and has co-founded five biotechnology companies. Dr. Kalluri’s laboratory is dedicated to unraveling the fundamental principles governing cancer initiation, progression, and metastasis with specific emphasis on tumor microenvironment in the context of pancreatic ductal adenocarcinoma (PDAC), triple negative breast cancer (TNBC), and glioblastoma multiforme (GBM).

Kalluri Laboratory Research:                                                                                                                                                                                        
Cancer evolves to due to injury to the functional parenchyma in our body. While genetic injury, in the form of chromosomal rearrangements and gene alterations, are associated with cancer initiation and progression, the host response associated with genetic injury plays a critical role in the pathogenesis of cancer. Our laboratory is dedicated to unraveling the fundamental principles governing cancer initiation, progression and metastasis, with specific emphasis on tumor microenvironment in the context of pancreatic ductal adenocarcinoma (PDAC), triple negative breast cancer (TNBC) and glioblastoma multiforme (GBM). 

The efforts of the Kalluri laboratory since 1997 led to many discoveries related to mechanism of tissue injury and regeneration, vascular biology and tumor angiogenesis, and tumor microenvironment and exosomes biology (https://www.ncbi.nlm.nih.gov/pubmed/?term=kalluri+r), and some of these findings were translated into the clinic to benefit our patients. The laboratory discoveries unraveled new understanding of the biology of cancer, offered opportunities to work with pharmaceutical industry to develop new drugs, and contributed to the formation of new biotechnology companies in partnership with the institution in an effort to fight cancer.  Since moving to MD Anderson Cancer Center in 2012, the research from the Kalluri laboratory has been cited 31,876 times with an h-index of 83.  

The research in our laboratory continuously evolves to reflect the knowledge gained with each study completed and the emerging new scientific information. Such plasticity allows researchers in our laboratory to ask out-of-the box questions and constantly seek novel discoveries to develop new strategies in our fight against cancer. The students and post-doctoral fellows who join our laboratory bring fresh ideas and innovative concepts to initiate projects that drive their passion for discoveries. The current research focus of the laboratory is in the following areas: tumor microenvironment in cancer biology and metastasis; tissue injury, repair and regeneration; biology and function of exosomes in cancer.

Dr. Kalocsay completed his Ph.D. in Cell Biology and Biochemistry at the LMU University of Munich, Germany, and the Max-Planck Institute of Biochemistry, Munich. He completed a postdoctoral research fellowship with Steve Gygi at Harvard Medical School, Boston, before he was promoted to Instructor in Therapeutic Sciences and served as Director of Proteomics in the Laboratory of Systems Pharmacology at Harvard Medical School. In 2022, Dr. Kalocsay was recruited to MD Anderson as an Assistant Professor in the Department of Experimental Radiation Oncology. Dr. Kalocsay is the recipient of the prestigious CPRIT First Time Tenure Track Recruitment Award.

Kalocsay Laboratory Research:
The Kalocsay lab is using quantitative mass spectrometry to understand receptor signaling. We have pioneered proximity sensitive proteomics to precisely define functional interactions in situ at unprecedented temporal and spatial resolution and developed proximity phospho-proteomics to precisely follow protein phosphorylation during signaling. We plan to harness these breakthrough technologies to define receptor signaling using experimental models for tumor immune evasion in the future, with the goal of understanding disease mechanisms and developing new therapeutics.

The immune system normally eliminates early malignant cells, thus preventing tumorigenesis. Immune checkpoints prevent overactivation of the immune system, however tumors exploit these checkpoints to evade detection and clearance. Despite enormous clinical importance, we still have an incomplete understanding of which proteins participate in checkpoint signaling, how phosphorylation regulates checkpoint receptor signaling and how uncharacterized (orphan) checkpoint receptor ligands contribute to negative immune regulation.

We plan to leverage proximity-proteomics and mass spectrometry (MS) to study dynamics and aberrations of signaling processes in the context of immune checkpoints, pushing the envelope of existing MS technology. Through our innovative approaches we hope to elucidate ligand-specific differential immune signaling and decode differential phosphorylation in checkpoint signaling with the goal ultimately to better understand how the tumor micro-environment modulates receptor signaling.

Our new lab at MD Anderson is looking for highly motivated postdoctoral research fellows to elucidate cancer-relevant molecular mechanisms in Immune Checkpoint signaling. We apply top-notch quantitative multiplexed TMT mass spectrometry with newest instruments. Come join a great diverse team and help find innovative possible drug targets in cancer therapy.

Dr. Keyomarsi completed her Ph.D. in Biochemistry at UCLA (Los Angeles, CA) and her postdoctoral training at Harvard Medical School and Dana Farber Cancer Institute (Boston, MA).

Keyomarsi Laboratory Research:
The research in my laboratory is focused on the development of novel strategies for treatment and prognosis of breast cancer by combining experimental therapeutics with cell biology while targeting the cell cycle.  To this end, the laboratory is currently involved in the following areas of research which fall into translational and basic research categories.  

1) Cyclin E in breast cancer: Our laboratory was the first to discover that cyclin E, a key regulator in the G1/S transition is altered in breast cancer through the generation of low molecular weight (LMW) isoforms, a result of post-translational cleavage by the elastase class of serine proteases.  Specifically, we have developed in vivo models to examine the role of LMW-E in oncogenesis and discovered that the LMW-E isoforms are potent oncogenes that act early in the etiology of breast cancer [Cancer Research 2007 (PMID 17671189), 2 in 2010 (PMC2946214, PMC2888821), 2011(PMC3085722)].  We are also using these unique genetically engineered mouse models to interrogate the secondary oncogenic events induced by cyclin E early on in the neoplastic process [PLOS Genetics 2012 (PMC3315462), Cancer Research 2013 (PMC3773499)].Through the molecular analysis of the inducible murine transgenic model of LMW-E mediated tumorigenesis, we have mapped some of the early events in the pre-neoplastic mammary gland that gives rise to aggressive tumors with high metastatic potential. These events include induction of DNA damage, upregulation of several genes involved in unregulated DNA replication and G2/M transition, and specific mutations in genes, such as ALK, that is readily targetable. We then went on to elucidate the mechanism of LMW-E mediated tumorigenicity through identification and characterization of novel binding proteins and substrates for LMW-E. Protein microarray analysis identified the histone acetyltransferase (HAT) Hbo1 as a novel cyclin E/CDK2 substrate that mediates the cancer-stem-cell like phenotype. Other studies revealed that: Cyclin E is a downstream oncogenic target of PKCiota, and that activation of PKCiota by PI3K would further activate the signaling between PKCiota and cyclin [Oncogene 2016(PMC4856585)]; LMW-E is a mediator of HER-2 action in breast cancer and renders letrozole therapy ineffective in breast cancer cells that express both aromatase and ER [Oncogene 2010, (PMC2900397)]. Lastly, we identified ATP-citrate lyase (ACLY) as a novel interacting protein of LMW-E in the cytoplasm [Cancer Research 2016 (PMC4873469)]. LMW-E upregulates ACLY enzymatic activity and ACLY is required for LMW-E mediated transformation, migration and invasion in vitro, as well as tumor growth in vivo.  These studies suggest a novel interplay between LMW-E and ACLY and provide an unexpected link between metabolic pathways and the cell cycle in breast cancer. Our research in this area resulted in a clinical trial -NCT01624441.  More recently, we are investigating how the expression of LMW-E early in the pre-invasive breast cancer (i.e. ductal carcinoma in situ) results in induction of genomic alteration leading to an invasive carcinoma.  To this end we are currently examining the role of cytoplasmic cyclin E in differentiating indolent versus high-risk ductal carcinoma in situ (DCIS) in patients, and in cyclin E inducible cell lines and mouse models.  The successful completion of these studies will delineate those early oncogenic events in patients diagnosed with DCIS and provide the rationale to use LMW-E as a biomarker to identify the DCIS cases who could benefit from aggressive treatment, versus those (w/no cytoplasmic cyclin E) who can be monitored without the need for aggressive intervention.  

Our laboratory then went on to show that these LMW forms of cyclin E are prognostically relevant in breast cancer patients and their activity can be targeted. Early on, we established that overexpression of the LMW-E to be a strong predictor of poor survival in breast cancer using western blot analysis [NEJM 2002 (PMID: 12432043)]. Next, we set out to decipher if the cellular localization of the LMW-E was different than full length cyclin E. Our group discovered that through elastase mediated cleavage of full length cyclin E at two distinct sites in the amino terminus of the protein, the nuclear localization signal is lost in the LMW forms. Since cyclin E can only be degraded through its anchoring by FBW7 to the proteasome in the nucleus, we showed that not only do the LMW-E reside in the cytoplasm, but that they are much more stable than full length cyclin E, which is only found in the nucleus and subject to degradation [Cancer Research 2009  (PMC2669888)].  Based on this finding, we then hypothesized that through immunohistochemistry, we can differentiate if a tumor is expressing full length cyclin E (nuclear) or LMW-E (cytoplasmic). As a result of this finding, we thendeveloped a novel immunohistochemical (IHC) assay and scoring system for both LMW-E and p-CDK2 which successfullypredicted breast cancer recurrence-free and overall survival, suggesting that these two markers of G1/S transition be used as biomarkers for aggressive breast and bladder cancer [Am. Journal of Pathology 2016 (PMC4929404)]. Most recently, weexpanded these analyses and evaluated the subcellular localization of cyclin E in breast cancer specimens from 2,494 patients from 4 different cohorts and show that in multivariable analysis, cytoplasmic cyclin E staining was associated with the greatest risk of recurrence compared with other prognostic factors across all subtypes in all cohorts [Clinical Cancer Research 2017 (PMC5441976)].  We also show cytoplasmic cyclin E staining outperformed Ki67 and all other variables as prognostic factors [Clinical Cancer Research 2017  (PMC5768442)]. Collectively, these studies suggest that cytoplasmic cyclin E is likely to identify patients with the highest likelihood of recurrence consistently across different patient cohorts and subtypes [Invited Review in Cancer Research 2018 (PMC6168358)].  These patients may benefit from alternative therapies targeting the oncogenic isoforms of cyclin E. One such therapy is based on our findings on the mechanism of action of LMW-E through alteration in DNA damage response and repair pathways identified Wee1 kinase as suitable target for LMW-E expressing tumors [Clinical Cancer Research 2018 (PMC6317865)]. A clinical trial (NCT03253679 in collaboration with Dr. Siqing Fu and Funda Meric-Bernstam) which uses AZD1775-a Wee1 kinase inhibitor as a function of cyclin E status, has been recently approved and sponsored by both Astrazeneca and CTEP and is currently accruing patients [Expert Opin Investig Drugs (PMID: 30102076)]. 

2) Neutrophil Elastase and breast cancer metastasis:Our observation that LMW-E could be generated from full length-cyclin E by the serine protease neutrophil elastase (NE) was an unexpected finding. Our laboratory followed up on this finding and made the novel observation that elafin, a direct inhibitor of elastase, is regulated differentially in normal versus tumor cells thorough its transcriptional downregulation by C/EBPbeta [Cancer Research 2007 (PMID: 18056453)]. These studies revealed that elafin overexpression in tumor, but not normal cells, results in the preferential induction of apoptosis in the tumor cells and elafin can eradicate xenograft tumor growth in vivo. Moreover, we reported that downregulation of elafin sensitizes human mammary epithelial cells to exogenous NE-induced proliferation, suggesting that elafin is a counterbalance against the mitogenic effects of NE, including the intracellular generation of LMW-E [Cancer Research 2010 (PMC2940941), Oncogene 2015 (PMC4362782)]. These studies have set the foundation for our recent work where we found that in patients with breast cancer, high levels of NE is prognostic for poor overall, metastasis-free, and disease-specific survival (Breast Cancer Research 2014 (PMC4326485)]. We have also shown that genetic ablation of ELANE (gene encoding for NE) or inhibition of NE by a small molecule inhibitor has the benefit of diminishing metastasis in in vivo pre-clinical models of breast cancer. In collaboration with Dr. Stephanie Watowich (Immunology) we have established a direct molecular link between tumor associated neutrophils (TANs), tumor progression and metastasis mediated by NE and, significantly, highlight a targetable pathway via NE inhibition (NE inhibitor AZD9668) for therapeutic intervention in metastatic breast cancer. This project, which will address major gaps in our understanding of how TANs enhance breast cancer growth and metastasis. 

3) Mechanisms of action and resistance to CDK4/6 inhibitors: Deregulation of the CDK4/6-Cyclin D pathway in tumorigenesis has led to the development and FDA approval (palbociclib) of CDK4/6 inhibitors for the treatment of advanced estrogen receptor positive breast cancer. However, two major clinical challenges remain: i) adverse events leading to discontinuation of therapy and ii) lack of a reliable biomarker to predict response.  Our laboratory has recently discovered that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumorsin vivo. Furthermore, intact G1/S transition (Rb positive and LMW-E negative) is necessary and predictive of preclinical sensitivity to this drug combination and predictive of clinical response to palbociclib. Combined inhibition of CDK4/6 and autophagy was also synergistic in other solid tumor types with an intact G1/S checkpoint, providing a novel and promising biomarker-driven combination therapeutic strategy to treat breast and other solid tumors.  These studies [Nature Communications 2017 (PMC5490269)] resulted in the activation of a clinical trial (NCT03774472 in collaboration with Dr. Debu Tripathy-Breast Medical Oncology) examining the synergistic activity of an autophagy inhibitor when used in combination with palbociclib and endocrine therapy. 

More recently, our team have examined mechanisms of resistance to palbociclib and we reported (Clinical Cancer Research 2019 (PMID: 30867218)] that ER-positive breast cancer cells acquire resistance to palbociclib by downregulation of ER protein and DNA repair machinery and upregulation of the IL6/STA3 pathway, which is overcome by treatment with STAT3 and PARP inhibitors.  Matched biopsies from patients with breast cancer who progressed on palbociclib showed downregulation in DNA repair, ER, and IL6/STAT3 as compared with their pretreatment biopsy samples. By identifying and validating these mediators (or drivers) of palbociclib resistance, a novel treatment strategy with clinically available inhibitors to STAT3 and DNA repair is currently being designed by our laboratory and colleagues (Drs. Debu Tripathy and David Tweardy-Internal Medicine) to circumvent resistance and improve clinical outcomes. 

Eugenie S. Kleinerman, M.D., is Professor of the Division of Pediatrics. She is board certified in pediatrics, holds the Mary V. and John A. Reilly Distinguished Chair and is also a Professor of Cancer Biology. A native of Cleveland, OH, Dr. Kleinerman received her BA degree from Washington University in St. Louis, her medical degree from Duke University, then completed her pediatric residency at the Children’s National Medical Center in Washington, DC and her fellowship at the National Cancer Institute in Bethesda, MD. She was a Senior Investigator at the NCI-Frederick Cancer Research facility for 3 years before being recruited to MD Anderson in 1984. Dr. Kleinerman rose through the ranks from Assistant Professor to Professor. She served as Division Head of the Division of Pediatrics from 2001 to February 9, 2015, the first women Division Head at MD Anderson. 

Dr. Kleinerman is internationally recognized for my scientific and clinical expertise in sarcomas, (osteo and Ewing’s) and for her successes in translational research. Her 33 year career has focused on understanding the biology and mechanisms involved in the metastasis of osteosarcoma (OS) to the lung and identifying novel therapeutic strategies for both cancers. She pioneered the use of a unique immunotherapeutic agent, liposome-encapsulated muramyl-tripeptide (L-MTP), for children with relapsed OS lung metastases. Dr. Kleinerman's preclinical laboratory research, funded by R01 grants from the NCI, supported the initiation of phase I and phase II clinical trials done at MD Anderson Cancer Center. These trials demonstrated that L-MTP activated the tumoricidal properties of macrophages following administration, prolonged disease-free and overall survival in relapsed OS patients and could be combined with chemotherapy. The success of these trials led to a national phase III trial sponsored by the Children’s Oncology Group which demonstrated efficacy in patients that received L-MTP with chemotherapy, decreasing the mortality rate by 30% at 8 years. This phase III trial led to the approval of L-MTP by the European Medicine Agency (EMA). L-MTP is now part of standard treatment for OS patients in the UK, and other European countries, Mexico, South America, Turkey, and Korea. This demonstrates her success in translational research and identifies Dr. Kleinerman as an expert in the field of sarcoma translational research. Her preclinical research also demonstrated the efficacy of aerosol gene and aerosol chemotherapy against OS lung metastases by upregulating the expression of Fas on the tumor cell surface. These studies led to the initiation of clinical protocols using aerosol therapy. Her research program has been funded by the National Cancer Institute for over 30 years. She has >195 articles and 21 book chapters. 

Kleinerman Laboratory Research:

Dr. Kleinerman's career has focused on understanding the biology and mechanisms involved in Osteosarcoma (OS) lung metastasis and the pathways that control vascular development in Ewing’s sarcoma (ES). She has defined molecular pathways that control tumor vascular expansion, and the pathways that influence the metastatic potential of sarcoma to the lung. She developed a unique transplant model to identify how BM cells contribute to the vascular expansion in ES. She showed that vasculogenesis is critical to the expansion of Ewing’s vasculature; that EWS-FLI-1 transcriptionally down-regulated Caper-β which mediates alternative splicing of VEGF which is critical to the vasculogenesis process; that Notch signaling, DLL4, and the SDF-1a/PDGF-B pathway controlled the differentiation of BM cells into tumor vascular pericytes; that EWS-FLI-1 upregulated REST; and that REST controlled the formation of the ES vascular pericyte layer.  Dr. Kleinerman developed a mouse model of human OS lung metastases and demonstrated that Fas expression inversely correlates with the metastatic potential of OS cells. She demonstrated the efficacy of aerosol gene and chemotherapy against OS lung metastases which led to clinical protocols in pediatrics. She pioneered the use of immunotherapy in children with OS lung metastases, demonstrating that MTP-PE activated the tumoricidal properties of macrophages. Dr. Kleinerman led the phase II trials & was Co-PI in the phase III trial which showed that MTP + chemotherapy decreased the death rate by 30% at 8 years. Thus she has a successful track record of translating preclinical laboratory investigations into clinical trials. This Energy Balance (diet & exercise) research focus is a new area for her. She was recently awarded a Multidisciplinary Research Grant from the Institution on Energy Balance in Pediatric Oncology which provided the preliminary data. Dr. Schadler (Co-PI) and Dr. Kleinerman recently published 1 review article and have 1 research manuscript accepted for publication. Their goal is to decrease acute and late cardiotoxicity in Pediatric cancer patients.. 

Dr. Eugene Koay is a physician scientist at The University of Texas MD Anderson Cancer Center, who specializes in radiation therapy for patients with hepatobiliary and pancreatic cancers, and develops applications of the physical sciences to cancer for the purposes of early detection, biomarker development, and therapeutic management. He received a Bachelor of Science in Chemical Engineering from Rice University in 2001. He completed the MD/PhD Program at Baylor College of Medicine/Rice University in 2009, with a PhD in Bioengineering. His residency training was in Radiation Oncology at The University of Texas MD Anderson Cancer Center (2009-2014). He then joined faculty at MD Anderson where he established his clinical and research foci. He leads the Cancer Physics and Engineering Laboratory at MD Anderson.

Koay Laboratory Research:
This lab studies how the physical properties of tumors relate to the biological underpinnings of the disease. Recent work from the lab has shown how radiomics and artificial intelligence-based approaches may lead to clinically-relevant methods to stratify and manage hepatobiliary and pancreatic cancers (Koay et al, JCI, 2014; Amer et al , Cancer, 2018; Koay et al, Clin Cancer Res 2018). Dr. Koay’s lab also collaborates with mathematical modelers to apply physical models of therapeutic delivery (Pascal et al, Proc Nat Acad Sci, 2013; Butner et al, Sci Advances 2020) and tumor growth (Koay et al, Clin Cancer Res 2018). These studies describe how patient-specific parameters may be used to detect cancer earlier, predict treatment response, and improve cancer outcomes.

Dr. Koong earned his M.D. at Northwestern University and his Ph.D. in Cancer Biology from Stanford University, where he completed residency training in Radiation Oncology. He served in many capacities as research faculty and an attending physician at Stanford University for more than two decades before joining MD Anderson in 2017. Dr. Koong serves as Professor and Chair of the Department of Radiation Oncology and is the recipient of the Robert C. Hickey Endowed Chair for Clinical Care. He is a Fellow of both the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO). 

Koong Laboratory Research:
The Koong laboratory is a translational cancer research laboratory focused on the development of therapies to target signaling pathways regulated by the tumor microenvironment and to develop biomarkers that are predictive of clinical outcomes. Current clinical research interests are focused on the development and application of highly targeted radiotherapy techniques for gastrointestinal malignancies, particularly involving the use of stereotactic body radiotherapy (SBRT)/stereotactic ablative radiotherapy (SABR) for pancreatic and liver cancers. The Koong laboratory also studies the role of endoplasmic reticulum (ER) stress in tumor growth and metastasis.

Dr. Scott Kopetz received his medical degree from Johns Hopkins School of Medicine after an undergraduate degree in Electrical and Biomedical Engineering at Vanderbilt University. He obtained his residency training in Internal Medicine at Duke University Medical Center, followed by a medical oncology fellowship at M. D. Anderson Cancer Center. He subsequently completed a Ph.D. at M.D. Anderson in Cancer Biology.

Dr. Kopetz is currently Deputy Chair of the Department of Gastrointestinal Medical Oncology and Program Leader of the GI Program of the Cancer Center Support Grant at UTMDACC. He has authored over 300 peer-reviewed articles in respected scientific journals such as New England Journal of Medicine, Nature Medicine, Journal of Clinical Oncology, Lancet, Nature Reviews Cancer, Cancer Research, Lancet Oncology, Clinical Cancer Research, and JAMA. He is a senior editor for Clinical Cancer Research. Dr. Kopetz has developed a translational and clinical trial program in BRAF-mutated colorectal cancer, which has resulted in addition of combination therapy with a BRAF inhibitor to the current treatment guidelines. He also co-lead the clinical trial resulting in the FDA-approval of nivolumab and ipilimumab for mismatch repair deficient tumors. He also is an innovator in the development and implementation of circulating tumor DNA into clinical management, including interrogation of mechanisms of resistance, evaluation of minimal residual disease, and integration into clinical trial designs. Further research efforts include the development of the Consensus Molecular Subtypes, an RNA- based methodology for CRC classification that is now being widely integrated in retrospective and clinical trial efforts.

Kopetz Laboratory Research:
Dr. Kopetz is well versed in multidisciplinary care of and translational research for GI cancer patients. His laboratory is funded by multiple NIH-funded grants. He serves as chair of the Colon Cancer Task Force, and is Vice-Chair for Colon Cancer in the NSABP/RTG/GOG (NRG) Cooperative Group. Dr. Kopetz is a leader of the GI Cancer Center Support Grant at MD Anderson and the Colorectal Cancer Moonshot, a multi- disciplinary effort to improve the survival of this disease beyond incremental advances. 

Dr. Ma Received her Ph.D. from Memorial Sloan Kettering Institute and Cornell University - Weill Graduate School of Medical Sciences (New York, NY) and completed a postdoctoral fellowship in Cancer Biology at the Whitehead Institute for Biomedical Research (Cambridge, MA). 

Ma Laboratory Research:
The overarching goal of the Ma laboratory is to understand the molecular mechanisms of tumor progression and metastasis. Since its founding in 2010, the Ma Lab has played a major role in establishing models of microRNA-mediated regulation of metastasis, epithelial-mesenchymal transition, and therapy resistance (Nature Medicine 2012, PLoS Genetics 2014, Nature Communications 2014, Cancer Research 2016, etc), and in rectifying models of long non-coding RNA (lncRNA) regulation of metastasis (Nature Genetics 2018 – a paradigm-shifting study that establishes the framework for rigorous characterization of lncRNAs). In addition to RNA-related research, the Ma Lab also discovered the deubiquitinases for key cancer proteins; some of these deubiquitinases are promising anti-tumor and anti-metastatic targets (Nature Cell Biology 2013, Nature Cell Biology 2014, Cell Reports 2018, Nature Communications 2018, etc). Our work has been confirmed and cited by many groups (Dr. Ma’s Google Scholar citations: 10,000 as of 2018). Multiple former postdocs from this lab have landed independent faculty positions. 

Current interests include: (1) establishing new paradigms for RNA functions and mechanisms in tumor progression and metastasis; (2) screening for deubiquitinating enzymes that promote tumorigenesis, metastasis, or therapy resistance; and (3) investigating novel regulators and regulations of tumor radioresistance, drug resistance, and anti-tumor immunity. 

Dr. Maitra received his M.B.B.S. from All Indian Institute of Medical Sciences (New Delhi, India) and completed fellowships at Univeristy of Texas Southwestern Medical Center (Dallas, TX) in Anatomic Pathology, Molecular Pathology, and Pediatric Pathology. He completed his residency at UT Southwestern in Anatomic Pathology and a fellowship in Gastrointestinal Pathology at Johns Hopkins University School of Medicine (Baltimore, MD).

Maitra Laboratory Research:
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer-related mortality in the United States, accounting for over >37,000 deaths each year in this country, and is forecast to become the second most common cause of cancer-related deaths by 2030.  This alarming increase is already evident in the state of Texas, where the incidence of PDAC has risen by an astounding 32% over the last decade (http://www.dshs.state.tx.us/tcr).  Nationwide, the overwhelming majority of patients with PDAC (~85%) are diagnosed with distant metastases or with locally advanced disease, rendering them surgically inoperable.  Notably, even within the minority of pancreatic cancer patients that undergo surgical resection, as many as 70% will die of recurrence within the next two years.  This sobering statistic implies that PDAC is likely to invade and become “micrometastatic” at a relatively early stage of disease, which has been underscored by recent findings in experimental models.  As detailed in my curriculum vitae, the central themes of my research over the last decade have focused on the genetics and therapy of PDAC.  Thus, the multi-disciplinary translational research team, of which I am an integral member of at Johns Hopkins University, has elucidated the genomic landscape of not only PDAC, the most lethal primary malignancy arising from the pancreas, but also each of the individual variant tumors within this organ, such as pancreatic neuroendocrine tumors (PanNETs) and cystic neoplasms of the pancreas (Jones et al Science 2008; Jiao et al, Science 2011; Wu et al, Sci Transl Med 2011; Wu et al, PNAS 2011).  These unprecedented insights into the genome of pancreatic neoplasia over the last few years have now provided my own laboratory with unique opportunities to model the cognate entities in genetically engineered mice, with a long term goal of developing both early detection and targeted therapeutic approaches.  This prolific “team science” (recognized this year by the American Association for Cancer Research with the 2013 Team Science Award) is emblematic of the translational research approach I hope to bring to the Sheikh Ahmed Center for Pancreatic Cancer Research Center, of which I am the Scientific Director. 

 Selected research questions that my laboratory is pursing in translational PDAC research:

 Project 1: Functional annotation of the PDAC genome

The recent publication of the International Cancer Genome Consortium (ICGC) data on over 100 PDACs has established the definitive genetic landscape of PDACs (Biankin et al, Nature, 2012; Dr. Maitra is a member of this consortium).  The ICGC has identified numerous alterations that putatively cooperate with the near ubiquitous KRAS mutations in PDAC pathogenesis, including highly significant recurrent mutations of TP53, SMAD4, CDKN2A/p16, MLL3, ARID1A, TGFBR2, SF3B1, UTX, etc..  While the tumor suppressor role of several of the encoded proteins is well established (TP53, SMAD4, CDKN2A/p16), others remain virtually unknown vis-à-vis their function, and the effector pathways through which they participate in pancreatic carcinogenesis.  In many instances, even the overarching mechanism – tumor suppression versus oncogenic potentiation – remains unknown.  The importance of tissue specific contexts in gene function mandates that we explicitly interrogate the role of mutational alterations using cognate PDAC models.  These studies have already led to some unexpected insights in our laboratory.  For example, the mixed leukemia lymphoma (MLL) gene family encodes for histone methyltransferases, and typically undergoes gain-of-function (GOF) alterations in leukemia.  On the contrary, reported somatic mutations of MLL3 (observed in ~10% of PDAC) are loss-of-function (LOF), as evidenced by our data in human PDAC lines, as well as in a novel conditional mouse model of pancreas-specific Mll3 loss (unpublished data).  Further, we have identified a hitherto undescribed role for MLL3 protein in DNA repair, which suggests that tumors bearing somatic mutations of MLL3 might be susceptible to DNA damaging agents.  We are systematically querying recurrent alterations that cooperate with mutant KRAS in PDAC initiation and/or progression, using a broad compendium of in vitro and in vivo functional studies (such as in spontaneously metastatic orthotopic models and low-passage patient-derived human PDAC cell lines).  Effector pathways are being interrogated using a combination of global profiling approaches, including ChIP-Seq and RNA-Seq.  For the most compelling mutations, we are developing genetically engineered mouse models (GEMMs).  The availability of CRISPR/Cas9 systems for high efficiency introduction of targeted genomic deletions will allow us an opportunity to rapidly introduce LOF mutations in both PDAC cell lines and in autochthonous models.  Finally, given the overarching translational focus of our laboratory, we are performing high throughput screens for synthetic lethal interactions using either de novo or engineered mutations in PDAC lines.  Functional annotation of the most significant cooperating mutations with KRAS that contribute to pancreatic carcinogenesis will not only provide key biological insights into this lethal neoplasm, but also potential new avenues for therapeutic intervention.

 Project 2: Development of a “liquid biopsy” program in PDAC

In patients that present with either de novo or recurrent metastatic PDAC, a fine needle aspiration or a core needle biopsy is performed for diagnosis, but the acquired specimen is typically adequate for only perfunctory molecular assays.  More importantly, the nature of the specimen generally precludes the opportunity to establish a viable patient-specific preclinical model that can be used for elucidating molecular underpinnings of cancer recurrence and chemoresistance in advanced disease.  In fact, nearly all of the patient-derived xenograft (PDX) and cell lines in existence have been established from primary tumors, even as the major source of mortality in most patients remains metastases.  We are developing a “liquid biopsy” program in PDAC, which will enable the isolation of viable circulating tumor cells (CTCs) from a single vial of patient blood.  Studies published in the last year show that viable CTCs can be isolated and cultured ex vivo from patients with underlying solid tumors, such as lung and breast cancers, and the resulting preclinical models provide an effective surrogate for therapeutic decision making and predicting patient outcomes.  Through ex vivo molecular annotation combined with expansion of these CTCs in 3-D culture as spheroids, and in mice as PDXs, we hope to improve our understanding of mechanisms underlying genetic heterogeneity, patterns of tumor recurrence and treatment failure in patients with PDAC. 

 Project 3: Targeting tumor survival networks in the PDAC microenvironment

PDAC is unique amongst solid tumors in the floridness of its stromal response to invasion, a phenomenon labeled as desmoplasia.  The PDAC tumor microenvironment (TME), however, is comprised not only of cancer-associated fibroblasts (CAFs), but also a multitude of additional cell types, such as T- and B-cell subsets; and cells of granulocyte/monocyte lineage, including macrophages, mast cells, and myeloid-derived suppressor cells (MDSCs), amongst others.  Many of these cellular components have pertinent roles in the survival and dissemination of neoplastic cells.  At MD Anderson, my laboratory has initiated multiple projects directed at perturbing survival networks within the PDAC TME.  Salient examples include (a) dissecting the molecular and metabolic circuitries underlying paracrine interactions between neoplastic cells and the host TME; (b) generating a robust antitumor immune response by blocking co-inhibitory molecules expressed on the PDAC cell surface or immunosuppressive cytokines in the peritumoral milieu; (c) identification of immunogenic mutant epitopes on PDAC cells that can be targets of vaccine-induced adaptive immune response; and (d) high-throughput screens for identification of small molecules that can selectively deplete barriers to therapeutic efficacy in the PDAC TME, specifically drugs targeting CAFs and immunosuppressive MDSCs.  These, and other experiments, will be facilitated by our access to autochthonous models harboring the compendium of immune cells observed in human PDAC.   

H. Charles Manning is a chemist with a background in radiochemistry, medicinal chemistry and imaging science. He received his PhD from Texas Tech University at Lubbock, Texas, and completed his Postdoctoral Fellowship in Vanderbilt University, Nashville, Tennessee. He started his independent career at Vanderbilt University in 2006. During his tenure at Vanderbilt, Dr. Manning rose to the academic rank of Professor of Radiology, Chemistry, Biomedical Engineering, Neurosurgery, and Chemical and Physical Biology. In 2020, the Manning Laboratory relocated to MD Anderson Cancer Center in Houston, Texas. At MD Anderson, Dr. Manning is a Professor in the Department of Cancer Systems Imaging and serves as the Scientific Director of the Center for Advanced Biomedical Imaging (CABI) and Director of the Cyclotron Radiochemistry Facility in the Division of Diagnostic Imaging and co-leads the Institutional Theranostics Program. He is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar. 

Manning Laboratory Research:
The current directions of the Manning lab focus on quantifying cellular metabolism non-invasively through the use of high-affinity ligands for receptor-based targets and metabolic substrate transporters elevated in cancer cells. Spawning efforts into cancer drug development, Dr. Manning’s lab discovered the first potent and selective pharmacological inhibitors of ASCT2/SCL1A5, a glutamine transporter, including V-9302. This work has led to partnerships with industry and other academic labs to develop new small molecule therapies targeting glutamine metabolism in oncology and potentially other human diseases. Many projects in the Manning laboratory currently focus on molecular targets related to cancer cell metabolism and cell death, with emphasis on glutamine (Gln) metabolism, cholesterol metabolism, apoptosis, and autophagy. In addition to these biologically- and clinically-driven programs, the Manning laboratory is developing new radiochemistry technologies that enable dose-scale radiopharmaceutical production using inexpensive and disposable microfluidic devices. Beyond these and other specific research activities, the Manning lab acknowledges that the continued and future success of the field of molecular imaging is dependent upon training the next generations of physicians and scientists with expertise in molecular imaging, and specifically, radiochemistry. In fact, there is a tremendous shortage of individuals who have been formally trained in radiochemistry and related fields. For this reason, Dr. Manning is highly motivated to deploy unique education programs in radiochemistry and tracer development aimed at trainees at the undergraduate, graduate and post-graduate levels to address this critical shortfall.
 

Dr. Mazur received his BSc and MSc in Molecular Biology from Warsaw University in Poland. He earned his PhD in Molecular Biology and Cancer Research from Max Planck Institute of Biochemistry in Germany. Dr. Mazur joined the Departments of Genetics and Pediatrics at Stanford University for his Postdoctoral Fellowship, where he studied molecular mechanisms of MAPK signaling regulation in pancreatic cancer. He was promoted to Instructor in the Department of Pediatrics at Stanford University and later joined MD Anderson Cancer Center in the Department of Experimental Radiation Oncology as Assistant Professor.

Mazur Laboratory Research:
We are seeking strong candidates for high-impact, cross-disciplinary research projects within the pancreatic and lung cancer research program in our lab. Current projects are supported by several multi-year grants (NIH, CPRIT, AACR, AGA, LCRG) and in collaboration with industry (Sanofi) and private sponsors (Andrew Sabin Foundation) focused on the development of novel targeted and immuno-therapeutics, including:

Project 1. Adoptive immunotherapy (CAR-T cell-based therapy)
We work on basic and translational tumor immunology with focus on T cell biology and adoptive immunotherapy of cancer with the goal of developing new treatments for patients. The candidate will utilize advanced molecular biology techniques to improve the activity of immune cells and to investigate underlying mechanisms using realistic animal models and human samples. The Postdoctoral Fellow will work on creation of potent chimeric antigen receptors (CARs), and manipulation of co-stimulatory and signaling molecules. The Postdoctoral Fellow will be directly involved in translation of this work into the novel pre-clinical platform of adoptive immunotherapy for solid cancers. Our translational research platform takes advantage of immunocompetent pre-clinical mouse models integrated with Magnetic Resonance Imaging (MRI) for real time tumor monitoring and co-culture organoid tumor models using IncuCyte® live cell analysis system established in the lab (Nature Medicine, 2013, Nature Medicine, 2015, Cell, in press, 2018)

Project 2. Biochemistry (novel and “orphan” enzymes substrates discovery)
We aim to determine the functions and mechanisms of action of novel lysine methyltransferases in pancreas and lung tumorigenesis. Using CRISPR/Cas9 genetics screening we identified novel and “orphan” enzymes important in driving cancer progression and drug resistance. The Postdoctoral Fellow will utilize unique mouse strains that we have generated, cutting-edge proteomics, gene-editing and biochemical technologies, and the collaborative effort of our research groups (project performed in collaboration with Dr. Or Gozani’s Lab at Stanford University world class expert in proteomics and enzyme biology) to identify enzymatic activities and their function in cancer therapy (Nature, 2014 and Genes and Development 2016, Cell, in press, 2018). If warranted, the prospective Fellow will work with our collaborators at the Institute for Applied Cancer Science (IACS) to generate inhibitors targeting the identified enzymes for therapeutic intervention and test the compound using our established pre-clinical platform (Nature Medicine, 2015).

Project 3. Genetics and pharmacogenomics (multiplex CRISPR/Cas9 animal models of cancer)
We integrate CRISPR/Cas9-mediated genome engineering with conventional genetically-engineered alleles in mouse models of human lung and pancreatic cancers to create a high-throughput experimental pipeline to interrogate wide spectrums of tumor genotypes. Quantitative assessment of genotype-specific tumor responses to a panel of targeted therapies will generate a pharmacogenomic map that will guide patient treatment. The project is based on our recently published method for in vivo CRIPSR-mediated somatic-engineering in mice developed in collaboration with Dr. Tyler Jacks’ Lab at MIT (Nature Medicine, 2015). This method enables new comprehensive ways to combine mouse models and next-generation sequencing approaches to identify the dynamic interplay between specific tumor genotypes and the response to therapy. The project takes advantage of the “mouse clinic” approach utilizing pre-clinical mouse models integrated with MRI T2 real time tumor monitoring, as well as PDX and organoid tumor models established in Mazur lab (Nature Medicine, 2015).

Dr. Navin earned his Ph.D. in Molecular Genetics and completed his postdoctoral fellowship in Cancer Genetics from Cold Spring Harbor Laboratory and Stony Brook Univeristy (Cold Spring Harbor, NY).

Navin Laboratory Research:
My laboratory focuses on understanding the role of clonal diversity and evolution in the context of tumor progression in breast cancer.  Intratumor heterogeneity has been difficult to delineate in tumors using standard genomic methods that are limited to making bulk measurements that mask the genetic differences between cells and subpopulations.  To address this problem, we pioneered the development of the first single cell DNA sequencing method (Navin et al. 2011, Nature).  This study demonstrated the technical feasibility of sequencing the genome of a single mammalian cell.  This study played a central role in establishing the new field of single cell genomics, which has shown tremendous growth over the past 5 years due to myriad of applications in diverse fields of research and biomedicine.  My group continues to lead the cancer field of single cell genomics.  We have applied single cell sequencing technologies to study mutational evolution and aneuploidy in breast cancer patients.  Our studies revealed a punctuated model of copy number evolution in triple-negative breast cancer, in which complex aneuploid rearrangements are acquired in short evolutionary bursts at the earliest stages of tumor progression, followed by stable clonal expansions (Gao et al. 2016, Nature Gen.; Navin et al. 2011, Nature).  These data have challenged the long-standing paradigm of gradual copy number evolution during tumorigenesis.  Our group has also discovered a mutator phenotype in breast cancer cells that lead to the generation of many rare subclonal mutations that are likely to play an important role in therapy resistance (Wang et al. 2014, Nature).

Our group has remained at the forefront of the field, and continues to developed novel single cell DNA sequencing technologies to measure genome-wide copy number profiles (Baslan et al. 2012, Nature Prot), single cell whole genomes (Wang et al. 2014, Nature), single cell exomes (Leung et al. 2015, Genome Biol.) and multiplexed targeted panels in single cells (Wang and Leung et al. 2016, Nature Prot.).  We also have a major focus on developing computational methods to analyze large-scale single cell DNA sequencing datasets, including statistical methods for estimating copy number profiles (Baslan et al. 2012, Nature Prot; Wang et al. 2014, Nature), probabilistic methods to infer phylogenies (Gao et al. 2016 Nature Gen.; Davis et al. 2016, Genome Biol) and Bayesian likelihood genotype models for detecting DNA variants (Zafar et al. 2016, Nature Methods).  Current work is focused on using single cell DNA and RNA sequencing methods to study tumor initiation, invasion, metastasis, and therapy resistance in breast cancer. We also work closely with oncologists at MD Anderson to translate our single cell sequencing technologies into the clinic, for applications in early detection, non-invasive monitoring and improving diagnostic modalities.  These efforts are expected to have a major impact on reducing morbidity and improving the quality of life for breast cancer patients.

Dr. Piwnica-Worms received his Ph.D. in Cell Physiology and his M.D. at Duke University (Durham, NC) and completed his residency at Harvard Medical School and Brigham and Women's Hospital (Boston, MA) in Diagnostic Radiology, where he also served as Chief Resident. Dr. Piwnica-Worms completed his fellowship in Magnetic Resonance Imaging also at Harvard Medical School and Brigham and Women's Hospital and did his Postdoctoral Research Fellowship in Physiology at Duke University.

Dr. Piwnica-Worms (David) Laboratory Research:
Genomic lesions within incipient cancer cells in collaboration with alterations in the microenvironment contribute to neoplastic progression. Tumor cells can modulate the surrounding microenvironment to promote the progression of cancer through intrinsic oncogenic pathways. However, the importance of the host microenvironment in neoplastic progression, independent of tumor manipulation, is also underscored by studies demonstrating that many stromal and immune cell types stimulate growth of pre-neoplastic and neoplastic cells along with promoting drug resistance. Given these observations, understanding the complex interactions between genomic lesions and tumor microenvironment in animal models is crucial to understanding mechanisms of transformation and uncovering new anti-cancer therapies. Thus, non-invasive imaging technologies have become increasingly important for providing spatial and temporal resolution of biological structure and function, particularly for defining the context of gene expression and protein function, and their regulatory mechanisms within the proper physiologic context of cellular micro-environments. Molecular imaging is used to interrogate protein processing, protein-protein interactions, gene expression and flux through metabolic pathways in real-time in cells, live animals, and humans, and is an increasingly useful tool for understanding signal transduction, pharmacodynamics, and the pathobiology of human diseases in vivo, facilitating development of effective therapies.

Dr. Piwnica-Worms earned her Ph.D. in Microbiology and Immunology at Duke University (Durham, NC) and completed a Research Fellowship in Pathology  at Harvard Medical School and Dana-Farber Cancer Institute (Boston, MA).

Piwnica-Worms (Helen) Laboratory Research:
The major goals of my research program are to delineate how the cell division cycle is regulated in unperturbed cycling cells (cell cycle control); how cell division is delayed by replicative- and genotoxic stress (checkpoint control); how cancer cells derail these regulatory pathways; and ultimately to use this information to treat human disease.  Clinical, preclinical and basic studies in breast and prostate cancer are a major focus of the laboratory.  We are actively involved in designing and analyzing the results of Phase I/II clinical trials aimed at translating our fundamental knowledge of cell cycle- and checkpoint-control into improved targeted therapies for breast cancer patients.  Recognizing that a key challenge facing breast cancer researchers today is the lack of good preclinical models for studying human breast cancer, we are working with primary human breast tumors obtained directly from breast cancer patients.  These tumors are being propagated in the humanized mammary fat pads of immune compromised mice for our preclinical studies (HIM models).  Many of these models metastasize out of the mouse mammary gland to distant mouse organs, including bone and lung. We are identifying the molecular changes associated with the acquisition of metastasis in this model.  In addition, we are developing mouse models that enable regulatory pathways to be studied non-invasively and repetitively in living mice using molecular imaging strategies, with a particular focus on p21 and CDC25A.

Dr. Katy Rezvani is Sally Cooper Murray Chair in Cancer Research, Professor of Medicine, Chief of the Section for Cellular Therapy, Director of Translational Research and Medical Director of the GMP Facility at MD Anderson Cancer Center. She is the Principal Investigator on numerous grants and trials. Dr. Rezvani has over 150 peer-reviewed publications related to Immunotherapy, Cellular Therapy and Hematology/Oncology and hematopoietic transplantation. She has an active research laboratory program in transplantation immunology where the focus of her research group is to study the role of natural killer cells (NK) cells in mediating immunity against hematologic disorders such as acute leukemia and myelodysplastic syndromes as well as solid tumors, and to understand the mechanisms of tumor-induced NK cell dysfunction. The goal of these studies is to develop strategies to enhance NK cell effector function against tumors by genetically engineering the cells to enhance their in vivo antileukemic activity and persistence. She is the recipient of multiple grants and awards, and her laboratory program in transplant immunology has led to the approval and funding of a number of Phase I/II studies of immunotherapy in patients with hematologic malignancies as well as solid tumors such as glioblastoma.

Rezvani Laboratory Research:

1. Engineering NK cells as a novel cancer immunotherapy.
Current work in our laboratory centers on developing novel strategies to enhance NK cell effector function against various tumors by genetically engineering the cells to enhance their anti-cancer activity and persistence. We are pursuing this by engineering NK cells to express CAR against multiple cancer targets. Our laboratory recently demonstrated that ex vivo expanded NK cells expressing a CAR against CD19 and the IL15 gene can dramatically enhance the in vivo persistence and anti-tumor activity of CAR-NK cells in a mouse model of lymphoma. We have translated this strategy to the clinic and a first-in-human clinical trial is currently underway at our center. 

2. Adoptive cell therapy using viral specific T cells.
Another area of interest in our laboratory is the use of virus-specific T cells as adoptive therapy for the treatment of viral infection. Allogeneic stem cell transplantation is a potential curative treatment for hematologic malignancies including leukemia and lymphoma but a number of factor such as the high mortality rates associated with viral infection and graft vs host disease (GVHD) after transplant limit the clinical success. Our goal is to develop engineered T cells using different gene editing tools including TALEN or CRISPR to make them resistant to current cancer immunosuppressive drug regimens and use it as an off-the-shelf T cell therapy for immediate clinical use. Data from our clinical trial of off-the-shelf BKV-specific T-cells for the treatment of progressive multifocal encephalopathy (PML) was recently published in the New England Journal of Medicine.

We are also working on:
- Comprehensive analysis of NK cells and their receptors in cancer following hematopoietic stem cell transplantation using mass cytometry (CyTOF) and transcriptome profiling. 
- Understanding mechanisms of NK immune evasion and using gene editing tools ot target checkpoints to enhance NK effector function

Dr. Sharma is a trained medical oncologist and immunologist and the T.C. and Jeanette D. Hsu Endowed Chair in Cell Biology. Her expertise in Immunology and Genitourinary Medical Oncology enabled her to design and lead clinical trials with immune checkpoint therapy for patients with metastatic renal cell carcinoma and bladder cancer, which led to improved survival and approval of new treatments for these patients. To understand the impact of immune checkpoint therapy on human immune responses and to generate preliminary data with immune checkpoint therapy in the localized disease setting, she designed and conducted the first neoadjuvant (pre-surgical) trial with immune checkpoint therapy (anti-CTLA-4) in 2004. These studies led her to identify the ICOS/ICOSL pathway as a novel target for cancer immunotherapy strategies. Clinical trials targeting the ICOS/ICOSL pathway are currently ongoing. Dr. Sharma continues to design novel clinical trials to evaluate human immune responses to different immunotherapies and she is the Principal Investigator for multiple immunotherapy clinical trials that focus on translational laboratory studies. She was the first to demonstrate that human tumors express VISTA as an immunosuppressive pathway. Clinical trials targeting VISTA are currently ongoing. She was also the first to demonstrate that anti-CTLA-4 plus inhibition of EZH2 can improve anti-tumor responses, which led her to design a new clinical trial with this combination. This clinical trial is currently accruing patients. As a result of her expertise,     M. D. Anderson Cancer Center established the Immunotherapy Platform. She is a member of the American Society for Clinical Investigation (ASCI); received the Emil Frei III Award for Excellence in Translational Research in 2016; the Coley Award for Distinguished Research for Tumor Immunology in 2018; and honored with the Women in Science with Excellence (WISE) award in 2020.

Sharma Laboratory Research: 
Dr. Sharma is a nationally and internationally renowned physician scientist whose research work is focused on investigating immunologic mechanisms and pathways that impact tumor rejection. Dr. Sharma serves as the inaugural Scientific Director of the Immunotherapy Platform and she focuses her effort on a “reverse translation” process that encompasses studies on human immune responses to generate hypotheses related to mechanisms of tumor rejection, which she tests in appropriately designed pre-clinical models, and subsequently uses the new data to design novel clinical trials to improve outcomes for patients with cancer.

Dr. Andrew Sikora is a Professor of Head and Neck Surgery at MD Anderson Cancer Center in Houston, Texas. He also serves as Director of Research for Head and Neck Surgery. Dr. Sikora’s clinical expertise is in oropharyngeal (throat) cancer and human papillomavirus (HPV)-related head and neck cancer. His research is focused on tumor immunology, and cancer immunotherapy. Dr. Sikora serves as a member of the National Institute of Health (NIH) National Cancer Institute’s Head and Neck Cancer Core Committee, and Immuno-Oncology Translational Network (IOTN) Steering Committee.

Sikora Laboratory Research:                                                                                                                                                                                     
Dr. Sikora’s research focuses on understanding and reversing mechanisms of tumor-mediated immunosuppression; the immunobiology of HPV-related head and neck cancer; and the development of novel in vivo models for the study of tumor biology and therapeutic response. A consistent theme of Dr. Sikora’s laboratory-based research for the past decade is seeking to understand cancer-supporting aberrantly-regulated inflammatory processes occurring in the tumor immune microenvironment (TIME), and reversing these processes to enhance anti-tumor immunity Dr. Sikora has also served as the principle investigator of observational and therapeutic clinical trials designed to understand the impact of standard-of-care therapies on anti-tumor immunity, and to test novel immune-based therapies in head and neck cancer.                                                   

Dr. Sood received his M.D. at University of North Carolina (Chapel Hill, NC). He completed his residency at University of Florida - Shands Teaching Hospital (Gainesville, FL) in Obstetrics and Gynecology and was a Fellow in Gynecologic Oncology at University of Iowa Hospitals and Clinics (Iowa City, IA).

Sood Laboratory Research: 
My research focuses on mechanisms of cancer invasion and metastasis in ovarian and other cancers. Specifically, my research is focused in three main areas:

1) effect of neuroendocrine stress hormones on ovarian cancer growth and progression

2) development of novel anti-vascular therapeutic approaches

3) development of new strategies for in vivo siRNA delivery.

We are also interested in understanding the effects of platelets on tumor growth.  Our lab utilizes a wide range of in vitro and in vivo assays to study the topics described above.

Dr. Peter Van Loo is a Professor and CPRIT Scholar in Cancer Research at the University of Texas MD Anderson Cancer Center, Department of Genetics, with a joint appointment at the Department of Genomic Medicine. His research focuses on leveraging massively parallel sequencing efforts to study the evolutionary history of cancers. During his postdoctoral training at the University of Oslo, the University of Leuven, and the Wellcome Trust Sanger Institute, Peter developed computational techniques to study copy-number alterations in cancer genomes, and approaches to study the evolutionary history and subclonal architecture of tumors from whole-genome sequencing data, a field coined “molecular archeology of cancer”. Prior to joining MD Anderson, Peter was a Group Leader at the Francis Crick Institute in London, UK, where he still leads a research group. His work there has sketched the typical evolutionary trajectories of many cancer types, allowing insight into the timelines of cancer development, as well as insight into how tumors metastasize. Peter was the main lead of Evolution and Heterogeneity working group of the Pan-Cancer Analysis of Whole Genomics (PCAWG) Consortium, and is the genomics lead of the Sarcoma arm of the 100,000 Genomes Project. Peter has been awarded a Cancer Research UK Future Leaders in Cancer Research Prize in 2015 and a VIB Alumni Award in 2017.

Van Loo Laboratory Research:
The Cancer Genomics and Evolution laboratory headed by Prof. Van Loo aims to answer the key question “How do tumors evolve?”Cancer is caused by somatic changes to the genome. Breakthrough sequencing technologies now enable us to compare the genomes and epigenomes of cancer cells to those of normal cells to base-pair resolution. This in theory allows us to identify all (epi)genomic changes in a cancer cell, providing a unique opportunity to look at the genes and processes involved in cancer. As genomic changes occur throughout a tumor's lifetime, a cancer's genome is also an archeological record of its past, allowing a unique view of the tumor's evolutionary history. The Van Loo lab aims to reconstruct cancer’s evolutionary record to gain insight into the development and evolution of cancer, and into how tumors metastasize.Recent successes of the laboratory include pan-cancer studies of the evolutionary history of cancer (Gerstung et al., Nature 2020), intra-tumor heterogeneity (Dentro et al., Cell 2021), the mutational landscape in non-unique regions of the human genome (Tarabichi et al., Nature Biotechnology 2021) and biallelic mutations in cancer genomes (Demeulemeester et al., Nature Genetics 2022). Projects in the Cancer Genomics and Evolution laboratory focus around three big themes:
1. Inferring the evolutionary history and subclonal architecture of cancers from their genomes, through bulk whole-genome sequencing, single-cell sequencing, or a combination of both.
2. Development and large-scale application of novel approaches to study intra-tumor heterogeneity and tumor evolution from other omics layers, such as RNA sequencing and bisulfite sequencing.
3. Cancer genes and mutational processes in cancer, with a focus on identifying novel rare cancer genes, and on identifying, characterizing, and timing mutational processes causing copy number changes and complex structural variants in cancer evolution.

Dr. Wang is a Professor of Bioinformatics and Computational Biology and Biostatistics at the University of Texas MD Anderson Cancer Center. She received her PhD from Johns Hopkins University and performed postdoctoral training in statistical genomics and genome technology at UC Berkeley with Terry Speed and at Stanford with Ron Davis. Wenyi's research includes significant contributions to statistical bioinformatics in cancer, including MuSE for subclonal mutation calling, DeMixT for transcriptome deconvolution, Famdenovo for de novo mutation identification, and more recently, a pan-cancer characterization of genetic intra-tumor heterogeneity in subclonal selection. Her group is focused on the development and application of computational methods to study the evolution of the human genome as well as the cancer genome, and further develop risk prediction models to accelerate the translation of biological findings to clinical practice. 

Wang Laboratory Research:                                                                                                                                                                                         
The Wang laboratory is interested in 1) Deconvolution and single-cell modeling for intra- and inter- tumor heterogeneity and 2) Semi-parametric survival modeling for cancer risk prediction.

Dr. Wargo’s career commitment is to advance the understanding and treatment of disease through science. After completing her medical degree, she entered surgical residency training at the Massachusetts General Hospital/Harvard Medical School where she became interested in the biology and treatment of cancer. During her training, she completed 2 fellowships in surgical oncology with a focus on immunotherapy for cancer.Dr. Wargo was recruited to the Division of Surgical Oncology at Massachusetts General Hospital in July 2008 and had an active research laboratory focusing on melanoma tumorigenesis and immunotherapy for cancer. One exciting finding involved data describing the effect of BRAF-targeted therapy on tumor antigen expression in melanoma as a basis for combining targeted therapy and immunotherapy in the treatment of this disease. Dr. Wargo validated those findings in patients treated with BRAF inhibitors. She has continued critical studies to better understand the effects of BRAF inhibition on immune responses in melanoma, and established a unique set of serial tumor biopsies and blood samples from patients enrolled on clinical trials on BRAF inhibitors. Through analysis of these samples, she contributed significantly to the world literature regarding resistance mechanisms and the effect of targeted therapy on anti-tumor immunity.

Wargo Laboratory Research: 
Jennifer A. Wargo, M.D. runs a translational research laboratory studying the genetics of melanoma and other cancers with the goal of understanding what allows them to grow, spread and evade the immune system. The  research of the Wargo Lab is focused on using genetic targeted therapy to arrest the growth of these cancers and to make them more visible to the immune system. The lab is currently developing clinical trials incorporating what she has learned in the laboratory to treat patients with cancer Her efforts in this regard have been nationally recognized, and she has several research grants for this work, including starting PRIME TR (Program for Innovative Microbiome and Translational Research). In addition to her important work in the laboratory, Wargo has focused on minimally-invasive surgical techniques for the treatment of skin diseases, including skin cancer. As part of the Surgical Oncology department at MD Anderson Cancer Center, she has contributed to improving management for patients with skin cancer and other skin disease.

Watowich Laboratory Research:
The Watowich lab at MD Anderson investigates fundamental mechanisms that regulate innate immune responses in cancer, and how cells in the innate immune system contribute to or suppress cancer growth, how innate cells affect response to cancer treatment, and roles for innate cells in immune-related adverse events (irAE) during cancer immunotherapy. We aim to utilize information from our studies to develop novel, highly effective anti-tumor therapies with low toxicity. We are specifically interested in understanding how dendritic cells, the professional antigen-presenting cells of the immune system, contribute to cancer eradication, immunotherapy responses, and irAEs.  Our primary tumor models include melanoma, osteosarcoma, and breast cancer. We combine our expertise in innate immune regulation with clinical and translational collaborators across MD Anderson, allowing us to bridge fundamental studies with pre-clinical models and translational advances in cancer treatment.

Dr. Yee completed his medical degree in Canada, residency at Stanford  and an oncology fellowship at the Fred Hutchinson Cancer Research Center/ UW in Seattle. He was appointed Professor in 2009. In 2013, he was recruited to MD Anderson Cancer Center as a CPRIT established investigator and director of Solid Tumor Cell Therapy. He is an elected member of the American Society of Clinical Investigators, recipient of Clinical Translational Scientist Award from Burroughs Wellcome Fund and Damon Runyon Cancer Research Foundation,  co-Leader of the Stand Up to Cancer- Immunotherapy Dream Team and Member of the Parker Institute for Cancer Immunotherapy.   

Yee Laboratory Research:
His research over the last 20 years pioneered a form of ACT known as endogenous T cell (ETC) therapy which sources T cells from the peripheral blood. Using enabling technologies in engineering, microfluidics and cell sorting, together with discoveries in T cell biology,  Dr. Yee demonstrated it was feasible to routinely isolate and expand antigen-specific memory T cells for the treatment of patients with cancer including melanoma, sarcoma,  pancreatic, breast, and ovarian cancer.  His lab has performed several first-in-human adoptive cell therapy studies and converges multidisciplinary approaches in bioengineering, metabolism, molecular immunology and cellular biology to develop immunotherapy strategies and adoptive cellular therapy, in particular, as a treatment modality for patients with malignant diseases. Translational and basic  research studies in the Yee Lab include T cell memory, hypoxia, mouse models of pancreatic cancer and antigen discovery. He also has a machine that goes ‘ping’ (a clinical grade MEMS-based microfluidics cell sorter).

Dr. Yu earned her M.S. in Neuro-Cardio Physiology and her M.D. at Capital University of Medicine (Beijing, China). She went on to earn her Ph.D. in Molecular Biology and Cancer Biology from MD Anderson UTHealth Graduate School of Biomedical Sciences.

Yu Laboratory Research:
My laboratory functions as a bridge connecting basic & translational cancer research to important issues in cancer patient care.  In the new era of personalized cancer therapy, several new challenges are emerging. Our research is focused on tackling these new challenges. First, we are dissecting mechanisms of resistance to targeted- and immuno- therapies, and designing counteracting strategies to make patients respond better to anti-cancer therapies. Second, we are decoding cancer metastasis, especially brain metastasis, and designing effective therapies based on mechanistic understanding. Third, we are developing early detection, prevention, and intervention strategies for breast cancer and colon cancers. For example, we are using 2D and  three-dimensional (3D) cell culture models and various preclinical animal models, including cancer cell xenograft, patient-derived xenograft (PDX), transgenic, and knockout mouse models, as well as tissue and plasma specimens from patients. Our recent research areas also include, but are not limited to, stem cells and breast cancer initiating cells, molecular imaging of cancer progression, dysregulation of i) metabolism, ii) tumor microenvironment; iii) epigenetic modifiers, and iv) immune responses, and their roles in cancer progression, metastasis, and resistance to therapies.

Dr. Zhang is the Chair of Experimental Therapeutics at The University of Texas MD Anderson Cancer Center. He holds the John M. O'Quinn Endowed Chair in Cancer Research. Dr. Zhang received his Ph.D. in Cell Biology from the Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Science. His postdoctoral training came from the Institute for Cancer Research, Fox Chase Cancer Center, where he later became an Assistant Professor. He joined The Wistar Institute as an Associate Professor in 2012, was promoted to Professor in 2015 and later became holder of the Christopher M. Davis Endowed Professor & Leader, Immunology, Microenvironment and Metastasis Program. He assumed various leadership roles during his time at Wistar and was appointed Deputy Director in 2017. He joined The University of Texas MD Anderson Cancer Center as a Professor and Chair of Department of Experimental Therapeutics in 2023. Dr. Zhang is committed to finding a cure for epithelial ovarian cancer, the most lethal gynecological malignancy in the developed world. In addition, he investigates the aging process of normal mammalian cells and its role in both tissue aging and cancer development for the discovery of therapeutic applications.

Zhang Laboratory Research:
The Zhang laboratory studies ovarian cancer biology with the goal of developing novel therapeutic approaches to combat the disease with precision. In particular, the lab investigates how alterations in epigenetics— or the heritable changes that affects gene expression without alterations in the underlying DNA sequence—contribute to epithelial ovarian cancer. Despite great strides in identifying the various epigenetic enzymes/factors involved in cancer, the translational application of these findings in cancer intervention remains to be explored. For example, we are interested in epigenetic approaches to primer for and/or synergize with immunological therapy in epithelial ovarian cancer. The Zhang lab will pursue these issues in the coming years by focusing on the epigenetic SWItch/Sucrose Non-Fermentable (SWI/SNF) and PP2A complexes as proof of principles in the context of ovarian cancer. The ultimate goal of this line of investigation is to leverage these newly gained mechanistic insights for developing new therapeutics in a personalized manner based on one’s unique genetic and/or pathway signatures.

The Zhang laboratory also investigates the mechanisms that underlie aging in normal mammalian cells and how this process is implicated in tissue aging or evaded by tumor cells during malignant transformation. In particular, the lab focuses on epigenetic and metabolic pathways that regulate the aging process. For example, we are interested in how senescent cells modify tissue microenvironment through the senescence-associated secretory phenotype to affect tumor progression and therapy response. The overarching goal for identifying such mechanisms is the development of novel strategies to promote healthy aging and combat cancer.