Gan Laboratory
Boyi Gan, Ph.D.
Principal Investigator
Areas of Research
- Cancer Biology
- Cancer Metabolism
- Cell Signaling
- Genetics
- Immunotherapy
- Mitochondria
- Molecular and Cellular Oncology
- Targeted Therapy
- Radiation Therapy
- Tumor Suppression
The Gan Laboratory studies the intersection of cancer metabolism and cell survival/death, with the overarching goal of translating fundamental discoveries in metabolic biology into new therapeutic strategies for cancer.
Research Overview
Cancer cells must continuously adapt to metabolic stresses imposed by rapid growth, the tumor microenvironment, and cancer therapies. Our research seeks to understand how cancer cells survive or die under metabolic stress and how metabolic liabilities can be exploited to induce cancer cell death and overcome therapy resistance.
A major focus of our laboratory is metabolically regulated cell death. Our work spans three interconnected forms of cell death:
- ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation
- disulfidptosis, a form of cell death caused by disulfide stress
- cuproptosis, a copper-dependent form of cell death
By investigating how nutrient availability, metabolic pathways, redox homeostasis and metal metabolism regulate these cell-death processes, we aim to uncover fundamental principles governing cancer cell fitness and vulnerability.
Ultimately, our goal is to translate these discoveries into therapeutic interventions that exploit cancer-specific metabolic vulnerabilities and overcome resistance to cancer therapies, including radiotherapy and other treatment modalities.
Meet The Team
The Gan Laboratory is a research team comprised of research investigators, postdoctoral fellows and graduate students.
Selected Publications
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Cell
Cuproptosis-immunity crosstalk informs strategy to overcome immunotherapy resistance
Lei G, Lu Z, Xu Z, Braun C, Huo D, Gao J, Tan L, Hong T, Wu S, Sun M, Zhao X, Li Q, Chen X, Yan Y, Lee H, Mao C, Zhuang L, Ku L, Puebla N, Barsoumian H, Gan B.
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Nature Reviews Cancer
Exploiting metabolic cell death for cancer therapy
Chao M, Dadi J, Koong A, Gan B.
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Nature Reviews Molecular Cell Biology
Redox-driven cell death by disulfidptosis and its therapeutic potential
Gan B.
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Cancer Cell
Radiotherapy promotes cuproptosis and synergizes with cuproptosis inducers to overcome tumor radioresistance
Lei G, Sun M, Cheng J, Ye R, Lu Z, Horbath A, Huo D, Wu S, Alapati A, Aggarwal S, Xu Z, Mao C, Yan Y, Yao J, Li Q, Chen X, Lee H, Zhuang L, Jiang D, Pataer A, Gan B.
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Molecular Cell
Unraveling ETC complex I function in ferroptosis reveals a potential ferroptosis-inducing therapeutic strategy for LKB1-deficient cancers
Mao C, Lei G, Horbath A, Wang M, Lu Z, Yan Y, Liu X, Kondiparthi L, Chen X, Cheng J, Li Q, Xu Z, Zhuang L, Fang B, Marszalek J, Poyurovsky M, Olszewski K, Gan B.
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Cancer Cell
The roles of ferroptosis in cancer: Tumor suppression, tumor microenvironment, and therapeutic interventions
Lei G, Zhuang L, Gan B.
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Cancer Discovery
BRCA1-mediated dual regulation of ferroptosis exposes a vulnerability to GPX4 and PARP co-inhibition in BRCA1-deficient cancers
Lei G, Mao C, Horbath A, Yan Y, Cai S, Yao J, Jiang Y, Sun M, Liu X, Cheng J, Xu Z, Lee H, Li Q, Lu Z, Zhuang L, Chen MK, Alapati A, Yap T, Hung MC, You M, Piwnica-Worms H, Gan B.
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Nature Communications
Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance
Lee H, Horbath A, Kondiparthi L, Meena JK, Lei G, Dasgupta S, Liu X, Zhuang L, Koppula P, Li M, Mahmud I, Wei B, Lorenzi P, Keyomarsi K, Poyurovsky M, Olszewski K, Gan B.
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Nature Communications
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells
Yan Y, Teng H, Hang Q, Kondiparthi L, Lei G, Horbath A, Liu X, Mao C, Wu S, Zhuang L, James You M, Poyurovsky MV, Ma L, Olszewski K, Gan B.
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Nature Cell Biology
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis.
Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, Olszewski K, Horbath A, Chen X, Lei G, Mao C, Wu S, Zhuang L, Poyurovsky MV, James You M, Hart T, Billadeau DD, Chen J, Gan B.
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PNAS
A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria.
Wu S, Mao C, Kondiparthi L, Poyurovsky M, Olszewski K, Gan B.
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Nature Communications
A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers
Koppula P, Lei G, Zhang Y, Yan Y, Mao C, Kondiparthi L, Shi J, Liu X, Horbath A, Das M, Li W, Poyurovsky M, Olszewski K, Gan B.
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Nature Reviews Cancer
Targeting ferroptosis as a vulnerability in cancer
Lei G, Zhuang L, Gan B.
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Journal of Cell Biology
Mitochondrial regulation of ferroptosis
Boyi Gan
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Nature
DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer
Mao C, Liu X, Zhang Y, Lei G, Yan Y, Lee H, Koppula P, Wu S, Zhuang Li, Fang B, Poyurovsky M, Olszewski K, Gan B.
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Nature Communications
mTORC1 couples cyst(e)ine availability with GPX4 protein synthesis and ferroptosis regulation.
Zhang Y, Swanda R, Nie L, Liu X, Wang C, Lee H, Lei G, Mao C, Koppula P, Cheng W, Zhang J, Xiao Z, Zhuang L, Fang B, Chen J, Qian S, Gan B.
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Nature Cell Biology
Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer.
Liu X, Olszewski K, Zhang Y, Lim EW, Shi J, Zhang X, Zhang J, Lee H, Koppula P, Lei G, Zhuang L, You MJ, Fang B, Li W, Metallo CM, Poyurovsky MV, Gan B.
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Nature Cell Biology
Energy stress-mediated AMPK activation inhibits ferroptosis.
Lee H, Zandkarimi F, Zhang Y, Meena JK, Kim J, Zhuang L, Tyagi S, Ma L, Westbrook TF, Steinberg GR, Nakada D, Stockwell BR, Gan B.
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Cell Research
The Role of Ferroptosis in Ionizing Radiation–Induced Cell Death and Tumor Suppression.
Lei G, Zhang Y, Koppula P, Liu X, Zhang J, Lin SH, Ajani JA, Xiao Q, Liao Z, Wang H, Gan B.
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Nature Cell Biology
BAP1 links metabolic regulation of ferroptosis to tumor suppression.
Zhang Y, Shi J, Liu X, Feng L, Gong Z, Koppula P, Sirohi K, Li X, Wei Y, Lee H, Zhuang L, Chen G, Xiao Z, Jung M, Chen J, Huang P, Gan B.
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Nature Communications
Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development.
Xiao ZD, Han L, Lee H, Zhuang L, Zhang YL, Baddour J, Nagrath D, Wood CG, Gu J, Wu X, Liang H, Gan B.
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Journal of Biological Chemistry
The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate.
Koppula P, Zhang Y, Shi J, Li W, Gan B.
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PNAS
BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response.
Dai F, Lee H, Zhang Y, Zhuang L, Yao H, Xi Y, Xiao Z, You J, Li W, Su X, Gan B.
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Nature Cell Biology
LncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress.
Liu X, Xiao ZX, Han L, Lee SW, Wang W, Lee H, Zhuang L, Chen J, Lin HK, Liang H, Gan B.
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Nature
Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells.
Gan B, Hu J, Jiang S, Liu Y, Sahin E, Zhuang L, Fletcher-Sananikone E, Colla S, Wang YA, Chin L, Depinho RA.
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Cancer Cell
FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis.
Gan B, Lim C, Chu G, Hua S, Ding Z, Collins M, Hu J, Jiang S, Fletcher-Sananikone E, Zhuang L, Chang M, Zheng H, Wang YA, Kwiatkowski DJ, Kaelin WG Jr, Signoretti S, DePinho RA.