The University of Texas MD Anderson Cancer Center
Departments of Experimental Radiation Oncology & Molecular and Cellular Oncology
Targeting Ferroptosis and Metabolic Vulnerability in Cancer
My lab research is at the interface between cancer metabolism and cell survival/death. We are interested in the questions how cancer cell adapt to survive and grow under metabolic stress, and how to target metabolic vulnerabilities in cancer therapies. Our current research focuses on two related research topics: 1) the role and mechanisms of ferroptosis in cellular metabolism, tumor suppression, and cancer therapy, and 2) cystine metabolism-induced nutrient dependency and its implication in cancer therapy. Potential rotation projects include:
- Ferroptosis in cellular metabolism, tumor suppression, and cancer therapy
Our recent work has studied the regulatory mechanisms of ferroptosis, a form of cell death induced by lipid peroxidation, and its role in tumor suppression, cancer therapy, and cellular metabolism (Zhang et al., Nature Cell Biology, 2018; Lei et al., Cell Research, 2020; Lee et al., Nature Cell Biology, 2020; Zhang et al., Nature Communications, 2021; Mao et al., Nature, 2021; Gan, Journal of Cell Biology, 2021). Currently, we are applying integrated approaches, including metabolomic, lipidomic, and proteomic analyses and CRISPR screens, to gain deeper mechanistic understanding of ferroptosis and its interplay with cellular metabolism. We are also employing multi-disciplinary approaches, including sophisticated genetic mouse models, clinical investigation, and functional studies, to further dissect the role and mechanisms of ferroptosis in tumor suppression and to therapeutically target ferroptosis in cancer treatment.
- cystine metabolism-induced nutrient dependency and its implication in cancer therapy
Our recent study has also revealed an unexpected role of SLC7A11, the amino acid transporter that uptakes cystine and protects cells from ferroptosis, in promoting glucose dependency in cancer cells. Tumor cells with high expression of SLC7A11 are exquisitely sensitive to glucose starvation-induced cell death. Our study thus informs therapeutic strategies to target the metabolic vulnerability in tumors with high SLC7A11 expression (Liu et al., Nature Cell Biology, 2020; Zhang et al., Cancer Research, 2020; Koppula et al., iScience, 2021). Our current research efforts in this project include: 1) to therapeutically target SLC7A11-induced nutrient dependency and disulfide stress in SLC7A11-high cancers; 2) to further study SLC7A11-induced cell death under other metabolic stress conditions; 3) to employ CRISPR screens and other approaches to understand the nature and dissect the mechanisms of SLC7A11-induced cell death under glucose starvation; and 4) to study disulfide stress-initiated cellular signaling in SLC7A11-high cancer cells by conducting redox proteomic analyses.
Training Environment. My laboratory currently consists of ~10 trainees, including GSBS students, postdoc fellows, technicians, and research scientists. The lab environment allows extensive interactions between potential GSBS students and the PI as well as other trainees, but also encourages research independence development of potential students. Within this training environment, most trainees gain extensive training experience with high-profile publications. GSBS students have played a major role in our research program. For example, Pranavi Koppula, a GSBS student made the discovery that SLC7A11 regulates glucose dependency in cancer cells, and has had multiple first-author publications and received several awards/fellowships, such as CPRIT Graduate Scholar Award and Dr. John J. Kopchick Research Award. The lab research is currently supported by three R01s and several foundation grants.
Education & Training
PhD, Cornell University, 2006
cancer metabolism, ferroptosis, and cancer therapy