Boyi Gan, PhD
Department of Experimental Radiation Oncology, Division of Radiation Oncology
Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
Our lab studies the roles of nutrient sensing and metabolic stress in cancer and stem cells. Our previous studies, among others, have shown that the FoxO/TSC/LKB1 tumor suppressor network plays critical roles in energy sensing, cancer metabolism and stem cell maintenance (Gan B, et al, PNAS, 2008; Gan B, et al, Cell Cycle, 2008; Gan B, et al, Nature, 2010; Gan B, et al, Cancer Cell, 2011). These studies have delineated an intimate link between tumor suppressor pathways that control energy sensing and metabolism and those that regulate stem cell homeostasis, and pointed to the critical importance of coupling energy availability and tissue homeostatic demands.
Our recent studies focus on nutrient sensing and metabolic stress in cancer. Specifically, we are interested in the following questions:
1) How normal/cancer cells sense energy and nutrient availability?
2) How cancer cells adapt to survive and grow under metabolic stress?
3) How to target metabolic vulnerabilities in cancer therapies?
Our current research efforts are directed towards two major projects:
First, we have continued to study energy sensors LKB1-AMPK and FoxO pathways in metabolic stress response and cancer metabolism. These studies also uncovered novel regulatory mechanisms of long non-coding RNAs (lncRNAs) in regulating these pathways in energy sensing/metabolism and cancer development/treatment ( Lin A, et al, Oncogene, 2014; Lin A, et al, Cancer Research; Liu X, et al, Nature Cell Biology, 2016; Liu X, et al, Cell Cycle, 2016; Xiao Z, et al, Nature Communications, 2017; Chauhan, et al, FASEB Journal, 2019 ).
In addition, our recent work has studied the regulatory mechanisms of ferroptosis, a non-apoptotic cell death induced by metabolic stress, and its role in tumor suppression and cancer therapies. Our studies link the tumor suppressor BAP1 to metabolic stress response and ferroptosis regulation. Our work also revealed an unexpected role of SLC7A11, the amino acid transporter that uptakes cystine and protects cells from ferroptotic cell death, 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 (Dai F, et al, PNAS, 2017; Koppula P, et al, JBC, 2017; Zhang Y, et al, Nature Cell Biology, 2018; Zhang Y, et al, Cell Cycle, 2019).
We're employing multi-disciplinary approaches, including sophisticated genetic mouse models, integrated transcriptomic/genomic/metabolomic/computational analyses, detailed biochemical mechanistic studies, and clinical investigation to dissect these important questions. A deeper understanding of the biological processes linking energy sensing/metabolism to cancer will provide novel insight for cancer therapy.
For more information, please visit our lab webpage: https://www.mdanderson.org/research/departments-labs-institutes/labs/gan-laboratory/research.html
Education & Training
Degree-Granting Education
| 2006 | Cornell University, Ithaca, NY, USA, PHD, Comparative Biomedical Sciences |
| 2000 | Fudan University, Shanghai, CHN, MS, Genetics |
| 1997 | Fudan University, Shanghai, CHN, BS, Microbiology |
Postgraduate Training
| 2010-2011 | Instructor, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA |
| 2006-2010 | Postdoctoral Fellow, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA |
Experience & Service
Academic Appointments
Assistant Professor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2011 - 2017
Honors & Awards
| 2018 | MD Anderson Faculty Scholar Award, MD Anderson Cancer Center |
| 2017 | Anna Fuller Award, Anna Fuller Foundation |
| 2017 | Andrew Sabin Family Award, MD Anderson Cancer Center |
| 2013 | Gabrielle's Angel Foundation Award, Gabrielle's Angel Foundation for Cancer Research |
| 2013 | Ellison Medical Foundation New Scholar Award, Ellison Medical Foundation |
| 2012 | The LAM Foundation Pilot Award, The LAM Foundation |
| 2012 | Kimmel Scholar, Sidney Kimmel Foundation |
| 2012 | CONquer canCER Now Award, Concern Foundation |
| 2012 | CSCDB Faculty Scholar Award, Center for Stem Cell and Developmental Biology, UT MD Anderson Cancer Center |
| 2011 | DOD PCRP Exploration - Hypothesis Development Award, Department of Defense |
| 2011 | Harvard Chinese Life Science Annual Distinguished Research Award |
| 2010 | DOD TSCRP Career Transition Award, Department of Defense |
| 2009 | DF/HCC Kidney Cancer SPORE Career Development Award, DF/HCC Kidney Cancer SPORE |
| 2007 | Leukemia & Lymphoma Society Fellowship, Leukemia & Lymphoma Society |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Shen X, Wang R, Kim MJ, Hu Q, Hsu CC, Yao J, Klages-Mundt N, Tian Y, Lynn E, Brewer TF, Zhang Y, Arun B, Gan B, Andreeff M, Takeda S, Chen J, Park JI, Shi X, Chang CJ, Jung SY, Qin J, Li L. A Surge of DNA Damage Links Transcriptional Reprogramming and Hematopoietic Deficit in Fanconi Anemia. Mol Cell 80(6):1013-1024.e6, 2020. PMID: 33338401.
- Zhang Y, Shi J, Liu X, Xiao Z, Lei G, Lee H, Koppula P, Cheng W, Mao C, Zhuang L, Ma L, Li W, Gan B. H2A monoubiquitination links glucose availability to epigenetic regulation of the endoplasmic reticulum stress response and cancer cell death. Cancer Res 80(11):2243-2256, 2020. e-Pub 2020. PMID: 32273282.
- 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. Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. Nat Cell Biol 22(4):476-486, 2020. e-Pub 2020. PMID: 32231310.
- Lei G, Zhang Y, Koppula P, Liu X, Zhang J, Lin SH, Ajani JA, Xiao Q, Liao Z, Wang H, Gan B. The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression. Cell Res 30(2):146-162, 2020. e-Pub 2020. PMID: 31949285.
- 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. Energy-stress-mediated AMPK activation inhibits ferroptosis. Nat Cell Biol 22(2):225-234, 2020. e-Pub 2020. PMID: 32029897.
- Chauhan AS, Zhuang L, Gan B. Spatial control of AMPK signaling at subcellular compartments. Crit Rev Biochem Mol Biol 55(1):17-32, 2020. e-Pub 2020. PMID: 32069425.
- Lee H, Zhuang L, Gan B. Energy stress inhibits ferroptosis via AMPK. Mol Cell Oncol 7(4):1761242, 2020. e-Pub 2020. PMID: 32944623.
- Chauhan AS, Zhuang L, Gan B. Antagonism between Antiviral Signaling and Glycolysis. Trends Endocrinol Metab 30(9):571-573, 2019. e-Pub 2019. PMID: 31349923.
- Zhang Y, Koppula P, Gan B. Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell Cycle 18(8):773-783, 2019. e-Pub 2019. PMID: 30907299.
- Gan B. DUBbing Ferroptosis in Cancer Cells. Cancer Res 79(8):1749-1750, 2019. PMID: 30987975.
- Chauhan AS, Liu X, Jing J, Lee H, Yadav RK, Liu J, Zhou Y, Gan B. STIM2 interacts with AMPK and regulates calcium-induced AMPK activation. FASEB J 33(2):fj201801225R, 2019. e-Pub 2018. PMID: 30335546.
- Zhang Y, Zhuang L, Gan B. BAP1 suppresses tumor development by inducing ferroptosis upon SLC7A11 repression. Mol Cell Oncol 6(1):1536845, 2019. e-Pub 2018. PMID: 30788415.
- Kim J, Piao HL, Kim BJ, Yao F, Han Z, Wang Y, Xiao Z, Siverly AN, Lawhon SE, Ton BN, Lee H, Zhou Z, Gan B, Nakagawa S, Ellis MJ, Liang H, Hung MC, You MJ, Sun Y, Ma L. Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat Genet 50(12):1705-1715, 2018. e-Pub 2018. PMID: 30349115.
- 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 ZD, Hung MC, Chen J, Huang P, Li W, Gan B. BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nat Cell Biol 20(10):1181-1192, 2018. e-Pub 2018. PMID: 30202049.
- Xiao ZD, Han L, Lee H, Zhuang L, Zhang Y, Baddour J, Nagrath D, Wood CG, Gu J, Wu X, Liang H, Gan B. Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat Commun 8(1):783, 2017. e-Pub 2017. PMID: 28978906.
- Koppula P, Zhang Y, Shi J, Li W, Gan B. The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem 292(34):14240-14249, 2017. e-Pub 2017. PMID: 28630042.
- Jonasch E, Hasanov E, Corn P, Moss T, Shaw K, Stovall S, Marcott V, Gan B, Bird S, Wang X, Do K, Altamirano P, Zurita A, Doyle L, Lara P, Tannir NM. A Randomized Phase 2 Study of MK-2206 versus Everolimus in Refractory Renal Cell Carcinoma. Ann Oncol 28(4):804-808, 2017. e-Pub 2017. PMID: 28049139.
- Dai F, Lee H, Zhang Y, Zhuang L, Yao H, Xi Y, Xiao ZD, You MJ, Li W, Su X, Gan B. BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response. Proc Natl Acad Sci U S A 114(12):3192-3197, 2017. e-Pub 2017. PMID: 28275095.
- Liu X, Gan B. lncRNA NBR2 modulates cancer cell sensitivity to phenformin through GLUT1. Cell Cycle 15(24):3471-3481, 2016. e-Pub 2016. PMID: 27792451.
- Kim J, Siverly AN, Chen D, Wang M, Yuan Y, Wang Y, Lee H, Zhang J, Muller WJ, Liang H, Gan B, Yang X, Sun Y, You MJ, Ma L. Ablation of miR-10b Suppresses Oncogene-Induced Mammary Tumorigenesis and Metastasis and Reactivates Tumor-Suppressive Pathways. Cancer Res 76(21):6424-6435, 2016. e-Pub 2016. PMID: 27569213.
- Xiao ZD, Zhuang L, Gan B. Long non-coding RNAs in cancer metabolism. Bioessays 38(10):991-6, 2016. e-Pub 2016. PMID: 27550823.
- Liu X, Xiao ZD, Gan B. An lncRNA switch for AMPK activation. Cell Cycle May 6:1-2(15):1948-9, 2016. e-Pub 2016. PMID: 27152502.
- Xiao ZD, Liu X, Zhuang L, Gan B. NBR2: a former junk gene emerges as a key player in tumor suppression. Mol Cell Oncol 3(4):e1187322, 2016. e-Pub 2016. PMID: 27652330.
- Liu X, Xiao ZD, Han L, Zhang J, Lee SW, Wang W, Lee H, Zhuang L, Chen J, Lin HK, Wang J, Liang H, Gan B. lncRNA NBR2 engages a metabolic checkpoint by regulating AMPK under energy stress. Nat Cell Biol 18(4):431-42, 2016. e-Pub 2016. PMID: 26999735.
- Lee H, Dai F, Zhuang L, Xiao ZD, Kim J, Zhang Y, Ma L, You MJ, Wang Z, Gan B. BAF180 regulates cellular senescence and hematopoietic stem cell homeostasis through p21. Oncotarget 7(15):19134-19146, 2016. e-Pub 2016. PMID: 26992241.
- Wang W, Xiao ZD, Li X, Aziz KE, Gan B, Johnson RL, Chen J. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nature Cell Biology 17(4):490-9, 2015.
- Lin A, Yao J, Zhuang L, Wang D, Han J, Lam EW, TCGA Research Network, Gan B. The FoxO-BNIP3 axis exerts a unique regulation of mTORC1 and cell survival under energy stress. Oncogene 33(24):3183-94, 2014. e-Pub 2013. PMID: 23851496.
- Lin A, Piao HL, Zhuang L, Sarbassov dos D, Ma L, Gan B. FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor growth in response to pharmacological inhibition of the PI3K-AKT pathway. Cancer Res 74(6):1682-93, 2014. e-Pub 2014. PMID: 24448243.
- Hu J, Ho AL, Yuan L, Hu B, Hua S, Hwang SS, Zhang J, Hu T, Zheng H, Gan B, Wu G, Wang YA, Chin L, DePinho RA. Neutralization of terminal differentiation in gliomagenesis. Proc Natl Acad Sci U S A 110(36):14520-7, 2013. e-Pub 2013. PMID: 23918370.
- Rosborough BR, Raïch-Regué D, Matta BM, Lee K, Gan B, DePinho RA, Hackstein H, Boothby M, Turnquist HR, Thomson AW. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1 and regulatory T cell induction. Blood 121(18):3619-30, 2013. e-Pub 2013. PMID: 23444404.
- Keniry M, Pires MM, Mense S, Lefebvre C, Gan B, Justiano K, Lau YK, Hopkins B, Hodakoski C, Koujak S, Toole J, Fenton F, Calahan A, Califano A, DePinho RA, Maurer M, Parsons R. Survival factor NFIL3 restricts FOXO-induced gene expression in cancer. Genes Dev 27(8):916-27, 2013. e-Pub 2013. PMID: 23630076.
- Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik JH, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, Depinho RA. Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism. Cell 149(3):656-70, 2012. PMID: 22541435.
- Ding Z, Wu CJ, Jaskelioff M, Ivanova E, Kost-Alimova M, Protopopov A, Chu GC, Wang G, Lu X, Labrot ES, Hu J, Wang W, Xiao Y, Zhang H, Zhang J, Zhang J, Gan B, Perry SR, Jiang S, Li L, Horner JW, Wang YA, Chin L, DePinho RA. Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell 148(5):896-907, 2012. e-Pub 2012. PMID: 22341455.
- Zhang K, Li L, Qi Y, Zhu X, Gan B, DePinho RA, Averitt T, Guo S. Hepatic Suppression of Foxo1 and Foxo3 Causes Hypoglycemia and Hyperlipidemia in Mice. Endocrinology 153(2):631-46, 2012. e-Pub 2011. PMID: 22147007.
- Hu J, Hwang SS, Liesa M, Gan B, Sahin E, Jaskelioff M, Ding Z, Ying H, Boutin AT, Zhang H, Johnson S, Ivanova E, Kost-Alimova M, Protopopov A, Wang YA, Shirihai OS, Chin L, DePinho RA. Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer. Cell 148(4):651-63, 2012. PMID: 22341440.
- Wei H, Wei S, Gan B, Peng X, Zou W, Guan JL. Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes and Development 25(14):1510-1527, 2011. PMID: 21764854.
- Gan B, Hu J, Jiang S, Liu Y, Sahin E, Zhuang L, Fletcher-Sananikone E, Colla S, Wang YA, Chin L, Depinho RA. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 468(7324):701-4, 2010. PMID: 21124456.
- Zheng H, Ying H, Wiedemeyer R, Yan H, Quayle SN, Ivanova EV, Paik JH, Zhang H, Xiao Y, Perry SR, Hu J, Vinjamoori A, Gan B, Sahin E, Chheda MG, Brennan C, Wang YA, Hahn WC, Chin L, DePinho RA. PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas. Cancer Cell 17(5):497-509, 2010. PMID: 20478531.
- Liang CC, Wang C, Peng X, Gan B, Guan JL. Neural-specific deletion of FIP200 leads to cerebellar degeneration caused by increased neuronal death and axon degeneration. J Biol Chem 285(5):3499-3509, 2010. e-Pub 2009. PMID: 19940130.
- 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. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell 18(5):472-484, 2010. PMID: 21075312.
- Wei H, Gan B, Wu X, Guan JL. Inactivation of FIP200 leads to inflammatory skin disorder, but not tumorigenesis, in conditional knock-out mouse models. Journal of Biological Chemistry 284(9):6004-6013, 2009.
- Gan B, Sahin E, Jiang S, Sanchez-Aguilera A, Scott KL, Chin L, Williams DA, Kwiatkowski DJ, DePinho RA. mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization. Proc Natl Acad Sci U S A 105(49):19384-9, 2008. e-Pub 2008. PMID: 19052232.
- Martin N, Schwamborn K, Urlaub H, Gan B, Guan JL, Dejean A. Spatial interplay between PIASy and FIP200 in the regulation of signal transduction and transcriptional activity. Mol Cell Biol 28(8):2771-2781, 2008. e-Pub 2008. PMID: 18285457.
- Nagy T, Wei H, Shen TL, Peng X, Liang CC, Gan B, Guan JL. Mammary epithelial-specific deletion of the focal adhesion kinase gene leads to severe lobulo-alveolar hypoplasia and secretory immaturity of the murine mammary gland. J Biol Chem 282(43):31766, 2007. e-Pub 2007. PMID: 17716968.
- Gan B, Yoo Y, Guan JL. Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth. J Biol Chem 281(49):37321-37329, 2006. e-Pub 2006. PMID: 17043358.
- Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL. Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways. J Cell Biol 175(1):121-133, 2006. e-Pub 2006. PMID: 17015619.
- Wei H, Wang X, Gan B, Urvalek AM, Melkoumian ZK, Guan JL, Zhao J. Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle regulation. J Biol Chem 281(24):16664-16671, 2006. e-Pub 2006. PMID: 16617055.
- Gan B, Melkoumian ZK, Wu X, Guan KL, Guan JL. Identification of FIP200 interaction with the TSC1-TSC2 complex and its role in regulation of cell size control. J Cell Biol 170(3):379-389, 2005. e-Pub 2005. PMID: 16043512.
- Melkoumian ZK, Peng X, Gan B, Wu X, Guan JL. Mechanism of cell cycle regulation by FIP200 in human breast cancer cells. Cancer Res 65(15):6676-6684, 2005. PMID: 16061648.
- Wu X, Gan B, Yoo Y, Guan JL. FAK-mediated src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. Dev Cell 9(2):185-196, 2005. PMID: 16054026.
- Koppula P, Zhuang L, Gan B. Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. e-Pub 2020. PMID: 33000412.
Invited Articles
- Yadav RK, Chauhan AS, Zhuang L, Gan B. FoxO transcription factors in cancer metabolism. Semin Cancer Biol 50:65-76, 2018. e-Pub 2018. PMID: 29309929.
- Koppula P, Zhang Y, Zhuang L, Gan B. Amino acid transporter SLC7A11/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer. Cancer Commun (Lond) 38(12):12, 2018. e-Pub 2018. PMID: 29764521.
- Zhang Y, Gan B, Liu D, Paik JH. FoxO family members in cancer. Cancer Biol Ther 12(4):253-259, 2011. e-Pub 2011. PMID: 21613825.
- Gan B, DePinho RA. mTORC1 signaling governs hematopoietic stem cell quiescence. Cell Cycle 8(7):1003-1006, 2009. e-Pub 2009. PMID: 19270523.
- Gan B, Guan JL. FIP200, a key signaling node to coordinately regulate various cellular processes. Cell Signal 20(5):787-94, 2008. e-Pub 2007. PMID: 18036779.