Koong Laboratory
Albert C. Koong, M.D., Ph.D.
Principal Investigator
- Departments, Labs and Institutes
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Areas of Research
- Pancreatic Cancer
- Radiation Therapy
- Drug Development
- Immunotherapy
The major focus of the Koong Laboratory is to investigate hypoxia-regulated signaling pathways that contribute to tumor growth and resistance to anti-cancer therapy.
Our Research
The Koong Lab is supported by an experienced research team. We have previously shown that the IRE1alpha-XBP1 pathway, a key component of the unfolded protein response (UPR), was activated by hypoxia and endoplasmic reticulum (ER) stress. Since identifying IRE1alpha-XBP1 as a potential therapeutic target in cancer, our laboratory has completed a high throughput small molecule screen of >120,000 compounds for inhibitors of this pathway.
We identified a class of compounds that selectively inhibit IRE1alpha and demonstrate potent anti-cancer activity. We developed several computational biology methods of analyzing the drug screening data to improve the efficiency of drug discovery. We also completed a genome-wide siRNA screen to identify other genes that are required for the activation of IRE1alpha. Studies investigating the mechanisms of IRE1alpha activation will lead to the development of novel cancer therapeutics targeting this pathway.
Recently, we also identified a novel regulatory function of IRE1alpha in cellular sensitivity to ferroptosis, an iron-dependent form of non-apoptotic cell death, suggesting that targeting this pathway pharmacologically may be a novel therapeutic approach for alleviating tissue damages due to excessive ferroptosis, as well as for improving cancer therapy.
Dr. Koong's clinical interest is in the treatment of gastrointestinal malignancies, particularly pancreatic cancer. He has pioneered the use of stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) for pancreatic cancer. The translational focus of the Koong Laboratory is to identify cancer biomarkers that facilitate clinical decision making.
Novel role for IRE1α suggests its therapeutic potential for regulating ferroptosis
Recent research led by Dadi Jiang, Ph.D., and Albert Koong, M.D., Ph.D., discovered a novel role for IRE1α in regulating glutathione synthesis, which is crucial for protecting cells from oxidative damage and maintaining tissue health. By controlling the expression of key glutathione biosynthesis regulators, IRE1α can impact cell sensitivity to ferroptosis. These findings suggest that cell sensitivity to ferroptosis can be pharmacologically modulated by IRE1α inhibition, highlighting its therapeutic potential.
Learn more in Nature Communications.
Meet the Team
The Koong Lab
Top row: Tianyu Wang, Henry Meyer, Matthew Cribb, Dadi Jiang
4th row: Maya Ferrell, Jasper Chen
3rd row: Nefetiti Mims, Youming Gou, Liang Wang
2nd row: Ling Xia, Tara Fujimoto, Sahar Fattani
Bottom row: Xianzhou Song, Ayeisha Colon Ortiz, Albert Koong, Morgan Green
Funding
- 1U54CA274220-02, National Cancer Institute (NCI): Acquired Resistance to Therapy and Iron (ARTI) Center, Project 2: Tumor hypoxia promotes acquired resistance to radiation through ferroptosis inhibition
- RP190192, Cancer Prevention and Research Institute of Texas (CPRIT): Pharmacological targeting of the IRE1/XBP1 pathway for triple-negative breast cancer therapy
- 3P30CA016672, National Cancer Institute (NCI): Radiation Oncology and Cancer Imaging
- ROSI Particle Therapy Pillar Seed Award, Division of Radiation Oncology, The UT MD Anderson Cancer Center: Harnessing the Tumor Microenvironment and DNA Repair Defects Using He- and C-Ions for Enhanced Anti-tumor Immunity
- ROSI Immuno-Radiation Therapy Seed Award, Division of Radiation Oncology, The UT MD Anderson Cancer Center: Targeting the Tumor Microenvironment to Enhance Immunogenic Cell Death Induced by High-LET Proton Radiation Therapy for Pancreatic Cancer Treatment
Dr. Koong and colleagues working in his lab.
Selected Publications
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Nature Communications
IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis Opens a new window
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Practical Radiation Oncology, 2019
Radiation Therapy for Pancreatic Cancer: Executive Summary of an ASTRO Clinical Practice Guideline Opens a new window
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Pancreas, 2019
Predicting Pancreatic Cancer Resectability and Outcomes Based on an Objective Quantitative Scoring System Opens a new window
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Nature, 2018
Altered exocrine function can drive adipose wasting in early pancreatic cancer Opens a new window
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Molecular Cancer Research, 2018
A Human Genome-wide RNAi Screen Reveals Diverse Modulators that Mediate IRE1α-XBP1 Activation Opens a new window
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JAMA Oncology, 2018
Association of Alterations in Main Driver Genes With Outcomes of Patients With Resected Pancreatic Ductal Adenocarcinoma Opens a new window
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JCO Precision Oncology, 2017
Comprehensive Analysis of the Unfolded Protein Response in Breast Cancer Subtypes Opens a new window
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Journal of Chemical Information and Modeling, 2017
Chemical Space Mimicry for Drug Discovery Opens a new window
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Nature, 2016
Reprogramming the immunological microenvironment through radiation and targeting Axl Opens a new window
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Science Reports, 2016
Identification of Doxorubicin as an Inhibitor of the IRE1 XBP1 Axis of the Unfolded Protein Response Opens a new window
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Cancer, 2015
Phase 2 Multi-Institutional Trial Evaluating Gemcitabine and Stereotactic Body Radiotherapy for Patients with Locally Advanced Unresectable Pancreatic Adenocarcinoma Opens a new window
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Blood, 2011
Identification of an Ire1alpha Endonuclease Specific Inhibitor with Cytotoxic Activity Against Human Multiple Myeloma Opens a new window
Contact Us
Principal Investigator
Albert C. Koong, M.D., Ph.D., FACR, FASTRO
Professor and Division Head, Division of Radiation Oncology
Chair, Department of Radiation Oncology
Olga Keith and Harry Carothers Wiess Distinguished University Chair in Cancer Research
Office: 713-563-2300
The University of Texas
MD Anderson Cancer Center
Department of Radiation Oncology
1515 Holcombe Blvd.
Unit 1422
Houston, TX 77030-4009
Executive Assistant
Jaycelyn “Jaye” Ketchum
713-563-7432
jmketchum@mdanderson.org