Faculty Mentors

Krishna Bhat, Ph.D., assistant professor in the TMP department, will serve as a co-mentor for the T32 training grant. Dr. Bhat’s research is focused on understanding the molecular changes that underlie adult brain tumors, particularly glioblastomas (GBMs). Dr. Bhat’s laboratory has recently discovered the existence of two major, clinically relevant, molecular subtypes of glioma stem-like cells (GSCs). Of these, the mesenchymal GSCs are radio-resistant and dependent on a set of transcriptional regulators including the Hippo signaling pathway transcriptional co-activator TAZ, and the pro-inflammatory transcriptional factor NF-kB for their survival. Dr. Bhat is currently using genetic, biochemical and proteomic approaches to identify additional novel regulators of the mesenchymal subtype of glioma and understand how they contribute to therapy resistance. The long term goals of his laboratory is to a) identify novel biomarkers for this disease with a special emphasis on “Tumor Educated Platelet” derived RNA signatures as a means of liquid biopsy for GBM, b) elucidate the molecular network of master transcriptional regulators that promote mesenchymal transition and treatment resistance in GBM, and c) identify novel therapeutic vulnerabilities for GSCs.

Ann Killary, Ph.D., is the program director of the T32 training program along with Dr. Wistuba who is the co-program director for the program. Her laboratory is interested in functional genomic approaches to elucidate the genetic mechanisms underlying the initiation and progression of breast cancer. Her lab is currently focusing on the characterization of a novel tumor suppressor and polarity regulator DEAR1 discovered in her laboratory and its role in the development and progression of breast and pancreatic cancers as well as its mutation/loss of function as a biomarker of poor prognosis in breast cancer.

In addition, her laboratory is investigating the earliest pathways aberrant in pancreatic cancer for biomarker discovery. As a PI of a biomarker discovery laboratory through the NCI’s Early Detection Research Network, her laboratory developed a functional genomic pathways based approach for biomarker discovery that has led to biomarker panels that detect early stage pancreatic cancer in the blood.

Lawrence Kwong, Ph.D., is an assistant professor and will serve as a co-mentor in the training grant faculty. Dr. Kwong’s laboratory primarily seeks to define novel combination therapies against melanoma and cholangiocarcinoma. The basis of our work mainly leverages sophisticated mouse models, bioinformatics, and human samples to identify, test, and validate new modalities. Previous work focused on MEK and BRAF inhibitors for melanoma, and his current projects expand to immunotherapies and epigenetically-targeted therapies. A major interest is also the determination of drug resistance mechanisms from patient samples. The ultimate goal is to initiate clinical trials that will improve both patient survival and quality of life.

Sue-Hwa Lin, Ph.D., is a professor in TMP and will serve as mentor for this grant. Dr. Lin’s laboratory focuses on metastasis of prostate cancer cells to bone and the progression of prostate cancer in bone. Prostate cancer has a propensity to metastasize to bone and induce blastic bone lesions. Dr. Lin has used protein fractionation and proteomics a well as genomic arrays and RNAseq approaches to identify, in bone marrow samples from prostate cancer patients and in patient-derived xenografts, factors that may play significant roles in the progression of prostate cancer cells in bone. Dr. Lin has mentored more than 80 graduate students, 12 postdoctoral fellows, 10 Clinical Residents and Fellows, 24 instructors/Assistant Professors. Dr. Lin was the director of Career Development Program of MD Anderson prostate SPORE for the past 10 years.

Sendurai Mani, Ph.D., is an associate professor in TMP and co-director of Metastasis Research Center, as well as Center for Stem cell and Developmental Biology. Dr. Mani will serve as a mentor for this grant. Dr. Mani pioneered studies to elucidate the connection between the latent embryonic program epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs). His laboratory investigates the role of EMT and CSCs is the development of resistance to therapies and in cancer metastasis. Dr. Mani, in collaboration with Dr. Stacy Moulder (Breast Medical Oncology), Dr. John Heymach (Thoracic Oncology) and Dr. Wistuba (TMP) by targeting EMT and CSCs to treat tumor relapse and cancer metastasis. Dr. Mani and his team uses genomics, proteomic and systems biology approach for developing precision medicine for tumor relapse and cancer metastasis.

Subrata Sen, Ph.D., is a professor and deputy chair of TMP and will serve as a mentor for this grant. He is an internationally recognized expert in cancer genetics and genomics and has made landmark discoveries in the field on projects aimed at identifying genetic alterations in cancer and characterizing their functional significance in the tumorigenic transformation process. Dr. Sen’s pioneering research led to the discovery of the mitotic kinase Aurora A as an oncogene, and the initial elucidation of its dysregulation in cancer. Dr. Sen has firmly established the role of elevated Aurora A function in the tumorigenic transformation process and has performed translational studies on the utility of Aurora A as a biomarker for cancer progression in addition to characterizing Aurora A pathway proteins as putative therapeutic targets in several different cancer types. Currently, clinical trials are ongoing with Aurora inhibitors for cancer throughout the world including three at MD Anderson. An Aurora-A In situ hybridization assay of voided urine samples of bladder cancer patients for monitoring disease, developed by his lab and their collaborators at MD Anderson, has been licensed by Abbott Molecular Inc. and a patent for the assay has been issued. Dr. Sen’s laboratory has also been pursuing complementing functional genomic strategies to develop early detection biomarkers for cancer and published miRNA biomarker panels to discriminate pancreatic cancer from normal controls in the blood and in pancreatic cyst fluid.

Rama Soundararajan, Ph.D. , is an associate professor in the TMP department, and will be a co-mentor for this training program. Her research expertise is in contextual cellular signaling, and in the laboratory/preclinical testing of signaling modifiers that selectively target cancer metastases. Her current research involves: 1) molecular analyses to elucidate the mechanistic determinants of metastatic competence in breast/prostate carcinoma cells, and 2) development of targeted therapies for neuroendocrine prostate cancers and triple-negative breast cancers, including the testing/validation of patient-derived xenograft models to aid translation of the identified precision medicine approaches. Having received several national and international awards for outstanding scientific research, she has significant experience leading and managing multiple research groups/projects including serving as PI on several independent grants (from the NIH, NIDDK, the American Heart Association, as well as from UCSF), collaborated with multiple researchers and produced many high-impact peer-reviewed publications from these projects. Dr. Soundararajan serves as director of ITERT and has over 12 years of experience in graduate students and postdoctoral/clinical fellows training. She contributed to a unique educational experience at UCSF designed to inform clinical fellows about the practices of basic science research at the bench (Renal Research Conference Series). At MD Anderson, she directs the ITERT Journal Club, a highly successful instructor-led training platform. She is the recipient of the June 2016 Faculty Educator Award at MD Anderson in recognition of her significant contribution to teaching excellence.

Ignacio Wistuba, M.D., is professor and chair of TMP who serve as program co-director/PI with Dr. Killary, as well as a mentor. One of Dr. Wistuba’s major research interests is the elucidation of the molecular abnormalities involved in the pathogenesis and progression of lung cancer, and the development of cancer predictive biomarkers for therapy. His studies also include identifying new molecular targets, validating biomarkers for targeted therapy and immunotherapy (e.g., BATTLE trials, Lung Cancer Consortium trials, MD Anderson Strategic Alliances on clinical trials), and identifying molecular markers (genomic intra-tumor heterogeneity, oncogenes activation, tumor microenvironment) associated with lung cancer tumor development, progression, and metastasis development using annotated human specimens and state-of-the-art molecular pathology approaches. Furthermore, he has established an invaluable tissue bank resource for thoracic malignancies at MD Anderson with more than 4,000 frozen and archival lung cancer and airway epithelia specimens from patients and a database of clinical, pathologic, and molecular information associated with these samples. Additionally, he oversees the MD Anderson Institutional Tissue Bank and Research Histology Core facilities and the translational research team on a number of biomarker-driven clinical trials on precision medicine, including targeted therapy and immunotherapy, on solid tumors and hematological neoplasms.

Florence McAllister, M.D., is an assistant professor and will serve as a T32 co-mentor. She is director of the MD Anderson high risk clinic for inherited pancreatic cancer susceptibility and oversees mutation screening, and early detection for family members. She is a physician-scientist interested in immunoprevention and cancer prevention with focus in gastrointestinal (GI) malignancies. Her laboratory focuses on understanding the molecular and cellular mechanisms that regulate the recruitment of immune cells to the very early pancreatic pre-neoplastic lesions and the effect of these cells on the development and progression of pancreatic cancer. During tumor
initiation and development, recruited immune cells establish a dynamic and close interaction with the neoplastic epithelium as well as with the fibrotic stroma, ultimately affecting tumor behavior. Her lab has taken several approaches: 1) Use of genetically-engineered mouse (GEM) models that mimic the development of human pancreatic cancer to dissect the role of immune cells in the regulation of cancer development; 2) Generation of GEM-immune reporter mice with the goal of performing multi-parametric cell sorting on particular types of immune cells at early and late stage of tumorigenesis for transcriptome analysis and for imaging studies aimed to determine cellular location and dynamics; 3) Utilization of bone marrow transplantation to test the functionality of specific immune cells or molecules in GEM models of pancreatic cancer; and, 4) Molecular characterization of the immune and epithelial human cells obtained from patients with pre-neoplastic lesions and pancreatic cancer to confirm the human significance of the experimental findings.

Eduardo Vilar-Sanchez, M.D., is an assistant professor and physician-scientist, a medical oncologist by training, and a T32 mentor. His clinical expertise and practice is entirely focused in the care of patients diagnosed with colorectal cancer and families with hereditary colorectal cancer syndromes. His long term research goal is to identify novel chemopreventive interventions for patients diagnosed with colorectal cancers arising in a genetic background (hereditary syndrome). In order to accomplish this overarching goal, his lab is characterizing the genomic and transcriptomic landscape of polyps using next-generation sequencing approaches and identifying new targets using systems biology tools. In parallel, his research group has been systematically applying this workflow to genetically engineered mouse models that mimic the natural history of hereditary colorectal cancer syndromes to perform cross-species comparisons and validate novel preventive agents and biomarkers. By studying premalignant polypoid lesions in hereditary conditions, Dr. Vilar-Sanchez expects to impact the survival of these patients and families affected by these diseases, and also the general population, due to the fact that these conditions serve as a model to understand the biology of sporadic colorectal cancer.

Paul Scheet, Ph.D., is an associate professor, and will serve as a mentor on the training grant. His research involves cancer genomics, human genetics, epidemiology, statistics and computer science. He has an established track record of statistical methods development in the field of genetic epidemiology and a growing one in computational cancer biology and collaborations for discovery of germline genetic variation underpinning complex disease. In addition, his laboratory has established translational research projects pairing novel statistical methods (e.g. hapLOH, Vattathil & Scheet, 2013) and applied computational support (e.g. data analysis workflows) in the following projects: spatial-temporal resolution of the evolution of NSCLC via molecular profiling of the field of cancerization; identification of novel drivers of carcinogenesis through molecular characterization of premalignant colorectal polyps; cancer in silico drug discovery through systems biology; discovery of germline risk alleles for pancreatic cancer; and, molecular diagnosis of loco-regional metastasis.

Ralf Krahe, Ph.D., is a professor in the Genetics department and will serve as a mentor in this training grant. Research in the Krahe laboratory focuses on the identification and characterization of human disease genes and their mutations/variants, including inherited cancer syndromes (Li-Fraumeni Syndrome (LFS) and the myotonic dystrophies (DM), by classic and molecular genetics and genomics/computational approaches. The Krahe lab mapped a novel LFS predisposition locus to 1q23, the gene of which they are identifying the candidate gene. In p53 and non-p53 LFS, there is evidence for risk modifiers and factors in addition to the inherited susceptibility.
Dr. Krahe is using integrated approaches combining genomic and epigenomic profiling to dissect the complex genetic and epigenetic events underlying LFS tumorigenesis. To dissect the pathophysiological consequences of variant genes, his laboratory is generating suitable LFS mouse models. LFS predisposition and/or modifier genes may also be functionally important in other tumor types lacking a clear genetic predisposition. The molecular characterization and classification of sporadic cancers (head and neck and lung cancer, and gliomas) through genomics methodologies to identify genomic, epigenomic and transcriptomic changes underlying tumor initiation, progression and metastasis is another focus.

Sadhan Majumder, Ph.D., is a professor and will serve as a mentor on the T32 training program. Dr. Majumder’s laboratory studies biological mechanisms and then build on the lessons learned from those studies using multiple methods including genomics, bioinformatics, biochemistry, cell biology, and mouse genetics. The laboratory works in close collaboration between basic scientists and clinicians. One of the first projects in his laboratory focused on advancing understanding of the childhood brain tumor medulloblastoma (MB) as a foundation for patient-specific therapeutic approaches. Dr. Majumder discovered that the transcriptional repressor REST is aberrantly overexpressed in a subclass of MB tumors and that a unique role of REST in these MB tumors is to block differentiation of the cerebellar stem/progenitor cells. This work was exciting because his lab, using REST-VP16, and others, using HDAC- and DNMT1-inhibitors, could block REST function in MB. Dr. Majumder’s work then evolved into an investigation of the mechanisms of stemness in neural stem cells, muscle progenitor cells, embryonic stem cells and glioblastoma stem cells. Based on their understanding of these mechanisms, in one line of work, Dr. Majumder’s lab made the pivotal discovery of converting muscle progenitor cells into functional neurons before the iPS system was published. His other work involves developing “personalized” treatment regimens for glioblastoma patient care.

Nick Navin, Ph.D., is an associate professor who will serve as mentor in the T32. He is an internationally recognized scientist for his seminal work on developing and applying single cell sequencing techniques to study cancer. Dr. Navin conducted his graduate training at the Cold Spring Harbor Laboratory through a joint program with Stony Brook University. During this time, he developed the first genomic method to study spatial intratumor heterogeneity and showed that this approach could be used to reconstruct tumor evolution in breast Dr. Navin’s postdoctoral training was also performed at the Cold Spring Harbor Laboratory, under the mentorship of Dr. Michael Wigler, where he developed the first DNA single cell sequencing method (Navin et al. 2011, Nature). He applied this approach to study copy number evolution in triple-negative breast cancer, which revealed a punctuated model of chromosome evolution. This seminal study demonstrated the technical feasibility of single cell genome sequencing and helped to establish a new field of biology: single cell genomics. Dr. Nicholas Navin is currently an associate professor at the MDACC, where he holds a dual appointment in the Departments of Genetics and Bioinformatics. Dr. Navin is also the co-director of the MD Anderson Sequencing and Microarray Core Facility. His laboratory uses single cell sequencing methods to study clonal diversity and evolution in breast cancer, to understand complex biological processes including invasion, metastasis and the evolution of chemoresistance. He is collaborating closely with many clinical groups at MDACC to translate single cell sequencing technologies into the clinic to improve the diagnosis and treatment of breast cancer. Dr. Navin has been the recipient of many prestigious awards and fellowships, including the AAAS Wachtel Award, ACS Research Scholar Award, the Andrew Sabin Fellowship, the Wilson Stone Award, the Randall Innovator Award and the Damon-Runyon Innovator Award.

Scott Kopetz, M.D., Ph.D. 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. 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. He has authored over 300 peer-reviewed articles in respected scientific journals Scott Kopetz, M.D., Ph.D., 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.

Jason T. Huse, M.D., Ph.D., associate professor in the TMP department, will serve as a co-mentor for the T32 training grant. Dr. Huse and his research group are focused on characterizing the molecular mechanisms underlying primary and secondary brain cancer, with a specific focus on epigenetic and transcriptional mechanisms. Recent functional work from the Huse lab has delineated the epigenetic consequences of ATRX deficiency in malignant glioma, along with its impact on global genomic instability and the immune microenvironment. Multiple strategies for therapeutic targeting have emerged from this work, and additional pre-clinical studies are ongoing. Additionally, the lab is exploring early-stage etiological events in malignant glioma through extensive tissue profiling, correlating germline genetic polymorphisms with patterns of somatic alterations. Findings from these studies should inform downstream functional analyses directly implicating 3D-chromatin architecture in specific oncogenic events. Finally, the lab has performed extensive integrated molecular profiling of brain metastasis samples, identifying metabolic and immune-related phenotypes amenable to treatment strategies. Single-cell sequencing approaches are now being utilized to interrogate molecular heterogeneity within brain metastases and characterize its functional impact.

Timothy McDonnell, M.D., Ph.D., is a professor and will serve as mentor in the T32. His research program is devoted to mechanistic studies focused on clinically relevant issues including molecular mechanisms of therapeutic resistance. A variety of approaches are employed varying from histopathology to molecular biology. Until joining the Department of Hematopathology several years ago as Deputy Chair much of his research effort was devoted to studies of solid tumors, including cancers of the prostate and skin. Since joining MDACC his research focus has been reoriented to the study of hematolymphoid malignancies and the role of signaling events commonly altered in lymphoid malignancies such as those mediated by the sonic hedgehog and TP53 signaling axes. Further, his laboratory has devoted considerable effort to developing and adapting methodologies to undertake genome-wide assessments from human tumor samples, including archived formalin-fixed paraffin-embedded tissue. The ultimate goal of these studies is to enable rational stratification of patients with cancer and develop effective, mechanism-based therapies.

Anirban Maitra, M.D., M.B.B.S.,  is a professor of Pathology and TMP, and scientific director of the Sheikh Ahmed Pancreatic Cancer Research Center at MD Anderson, Houston (since August 2013). He will serve as mentor in this grant. Dr. Maitra is a board-certified pathologist, with specialty expertise in pancreatic and GI pathology. Dr. Maitra is PI of a NIH-funded laboratory dedicated to pancreatic cancer research. Dr. Maitra has extensive familiarity of working with, and leading, large diverse teams of investigators engaged in a focused area of research. Dr. Maitra is Co-Leader of the MD Anderson Pancreatic Cancer Moon Shot project a multi-disciplinary effort to improve the survival of this disease beyond incremental advances. The Moon Shot effort encompasses many of the highest priority areas for progress in pancreatic cancer identified by the NCI in a 2014 white paper, including Ras-targeted therapies, immuno-oncology, and early detection. Dr. Maitra’s career has been defined by contributions made in the spheres of genetics and molecular pathology of pancreatic cancer and its precursor lesions, mouse models of pancreatic neoplasia, and experimental therapeutics in pancreatic cancer. He has published over 300 peer-reviewed publications, three dozen book chapters, and a comparable number of invited editorials, the vast majority of which are focused on pancreatic cancer research and /or clinical care. He has also trained close to 40 postdoctoral fellows and graduate students, many of whom are now in independent faculty positions in the United States or worldwide.