Koong Laboratory
Albert C. Koong, M.D., Ph.D.
Principal Investigator
Areas of Research
- Pancreatic Cancer
- Radiation Therapy
- Drug Development
- Immunotherapy
The major focus of the Koong Laboratory is to investigate tumor microenvironment, especially 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. The current research directions in the lab include:
Targeting the IRE1alpha-XBP1 branch of the UPR: 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.
The role of metabolic cell death in tumor response to radiation therapy (RT): 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 (Jiang et al. Nature Communications 2024). We expanded our research to the broader topic of metabolic cell death, cell death due to metabolic imbalances of tumor cells (Mao, et al. Nature Reviews Cancer 2025) including ferroptosis, cuproptosis and disulfdptosis, in tumor responses to treatment, especially RT.
Interplay between hypoxia, Cancer-Associated Fibroblasts (CAFs) and macrophages in PDAC tumor microenvironment: M2 macrophages suppress anti-tumor T cell responses, which leads to favorable conditions for tumor growth. Previously we found that this effect was HIF-2a (HIF2) dependent and could be reversed with a small molecule inhibitor of HIF-2a called PT2399, a preclinical version of belzutifan, an FDA-approved HIF-2a inhibitor for use in VHL-mutant renal cell carcinoma (Garcia et al. Gastroenterology 2022). We are actively working to identify the paracrine factor(s) mediating this polarization effect on macrophages. We envision that by using our combination of in vivo mouse modeling and in vitro cell/organoid culture systems we will determine the role of hypoxia in various cell types within the PDAC tumor microenvironment, with the goal to identify potentially druggable targets, such as the fibroblast-macrophage signaling axis.
Combination of mutant KRAS/pan-RAS inhibition with RT in pancreatic cancer treatment: Dr. Koong's clinical interest is in the treatment of gastrointestinal malignancies, particularly pancreatic cancer (pancreatic ductal adenocarcinoma, or PDAC). 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, as well as more effective therapeutic strategies to improve SBRT. More recently, we have been testing the combination of mutant KRAS/pan-RAS inhibitors in clinical development with SBRT in pre-clinical PDAC models.
An integrated approach for multiomics/multiplex/spatial tumor analysis
We utilize advanced state-of-the-art technological platforms to empower our tumor analysis. Single-cell RNAseq (scRNAseq) provides a snapshot of the relative abundance and transcriptomic profiles of diverse cell types in the tumor microenvironment. Spatial transcriptomics resolves the spatial distribution of the diverse cell types and infer valuable cell-cell interactions. Spatial metabolomics measures the distribution and abundance of metabolites. Multiplex immunostaining like the COMET assay enables spatial evaluation of essential proteomic markers. When integrated, these platforms form a powerful toolset to delineate the complex tumor ecosystem for various research purposes.
Exploiting metabolic cell death for cancer therapy
Chao Mao, Dadi Jiang, Albert C. Koong & Boyi Gan
Nature Reviews Cancer (2025)
Resistance to cell death is a hallmark of cancer, driving tumour progression and limiting therapeutic efficacy. Metabolic cell death pathways have been identified as unique vulnerabilities in cancer, with ferroptosis being the most extensively studied, alongside the more recently discovered pathways of cuproptosis and disulfidptosis — each triggered by distinct metabolic perturbations. In this Review, we examine the molecular mechanisms and regulatory networks that govern these forms of metabolic cell death in cancer cells. We further examine the potential crosstalk between these pathways and discuss how insights gained and challenges encountered from extensive studies on ferroptosis can guide future research and therapeutic strategies targeting cuproptosis and disulfidptosis in cancer treatment. We highlight the complexity and dual roles of metabolic cell death in cancer and offer our perspective on how to leverage these cell death processes to develop innovative, targeted cancer therapies.
Novel role for IRE1α suggests its therapeutic potential for regulating ferroptosis
Dadi Jiang, Youming Guo, Tianyu Wang, Liang Wang, Yuelong Yan, Ling Xia, Rakesh Bam, Zhifen Yang, Hyemin Lee, Takao Iwawaki, Boyi Gan & Albert C. Koong
Nature Communications (2024)
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.
Meet the Team
Bottom row: Albert Koong
2nd row, front to back: Nefetiti Mims, Morgan Green
3rd row: Sashi K Kulatilaka, Parth Baware, Dadi Jiang
4th row: Tara Fujimoto, Lian Wang, Tianyu Wang
Top row: Ling Xia, Matthew Cribb, Henry Meyer
Collaborators
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NCI ARTNet
The NCI Acquired Resistance to Therapy Network (ARTNet)
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ARTI Center
Acquired Resistance to Therapy and Iron (ARTI) Center
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Gan Lab
Experimental Radiation Oncology, UT MD Anderson
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Lin Lab
Radiation Oncology, UT MD Anderson
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David Piwnica-Worms Lab
Cancer Systems Imaging, UT MD Anderson
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Dr. Pankaj Singh
The University of Oklahoma
Dr. Koong and colleagues working in his lab.
Getting to know Chief Scientific Officer Albert Koong, M.D., Ph.D.
As UT MD Anderson’s chief scientific officer (CSO), Albert Koong, M.D., Ph.D., provides the vision for and executive oversight of our research enterprise, including discovery science, clinical and translational research. He champions innovation, develops strong partnerships and provides focused leadership for the entire research enterprise. After serving in an ad interim capacity, Koong was officially appointed as the CSO in June 2026.
We spoke with him about his career, his passions and the future of cancer research at UT MD Anderson. Here’s what he had to say.
Your background is in radiation oncology. How did you get started?
After my first year in college, my roommates and I decided to find summer jobs so we could stay on campus for the summer. I cold-called 10 faculty members and asked if they had any work. The head of the Radiobiology division ended up hiring me, sight unseen, as the dishwasher in his lab.
Soon after starting, I met the other members of the lab, including the postdocs. Their work seemed much more interesting than mine. I quickly sought out other opportunities within the lab. By the end of the summer, I was assigned my own small research project. That summer research project turned into an honors thesis. I applied to medical school and then pursued a PhD. Ultimately, this experience kicked off my career as a physician-scientist.
What brought you to UT MD Anderson?
I spent my entire professional career – more than 30 years, counting my undergraduate days – at Stanford University before being recruited in 2017 to UT MD Anderson as the chair and eventually the division head of Radiation Oncology.
I never thought I would leave California, but if you’re offered an opportunity at UT MD Anderson, the No. 1 cancer center in the world, it’s difficult to say no.
So, my wife and I moved to Houston with our two younger children. They were just starting high school. Our oldest stayed in California for college. We didn’t know anyone in Houston. It was a bit of a leap of faith. But I felt embraced from day one. Hurricane Harvey hit shortly after we moved, and watching the community come together, I realized what a unique organization this is. When people are asked to step up, they really do.
UT MD Anderson is everything I thought it would be and more. The faculty and staff are world-class and recognized leaders in their fields. They’re completely focused on the mission. Many have a personal connection to cancer, and the commitment to our patients is clearly evident.
One of the events that I look forward to the most every year is UT MD Anderson’s Boot Walk to End Cancer®. This 1.2-mile walk is more than just a fundraiser. It is really a celebration of advancements that we’ve made in cancer care. It’s the only event that brings together our patients, our faculty, our staff and members of the community in solidarity to recognize progress. It’s a really powerful event that reflects so much of what I love about UT MD Anderson. I’m looking forward to walking with the CSO Boots for Breakthroughs Team on Nov. 14!
Tell us about your research.
Since joining UT MD Anderson, most of my work has been in leadership and administration, but my work in the clinic and the lab always remains an important part of what I do. My lab investigates cell signaling within the tumor microenvironment. Specifically, we’re focused on disrupting the adaptive changes within the tumor microenvironment that allow tumor cells to survive and proliferate. Our goal is to develop therapeutic strategies that selectively modulate survival and overcome resistance to cancer therapies. We generally utilize pancreatic cancer models, as this also aligns with my clinic.
What brings you joy outside of work?
No. 1 is family. My wife, Jenny, and I have raised three kids who are now young adults just beginning their own careers. It has been extremely rewarding to see them pursue their passions.
Aside from that, personally, I love all sports. When I was younger, I played tennis, basketball and volleyball. Now, I mostly play tennis and resist the urge to take up pickleball. I also love cycling, particularly mountain biking.
I love watching sports. I try to understand what goes through the athlete’s mind. I see many parallels between the skills necessary for athletic and scientific achievement. Both require expertise that takes years to develop and hone. Both require tremendous resilience to overcome the expected failures. Both require commitment in the face of uncertainty. Both require teamwork, collaboration, discipline and perseverance.
Contact Us
Principal Investigator
Albert C. Koong, M.D., Ph.D., FACR, FASTRO
Chief Scientific Officer, UT MD Anderson
Professor, Gastrointestinal Radiation Oncology
Sewell Family Distinguished University Chair in Cancer Research
Office: 832-817-4354
Address
UT MD Anderson
Department of Radiation Oncology
1515 Holcombe Blvd.
Unit 1422
Houston, TX 77030-4009
Executive Office Administrator
Dana D. Hedge
832-817-4354
DDHedge@MDAnderson.org