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Boyi Gan, PhD

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

 Most cancer cells exhibit dramatic alterations in energy metabolism and nutrient uptake in order to support increased cell growth and proliferation, which is known as the Warburg effect. Indeed, many cancer mutations lead to dramatic changes, or reprogramming, in cellular metabolism and bioenergetics, establishing an intimate link between cancer development and cell metabolism. Notably, some cancer genes which play critical roles in cancer metabolism also function to control longevity and stress resistance in lower organisms. Given that stem cell homeostasis is required for mammals to ensure tissue maintenance and long-term survival under aging or stress conditions, there is likely to be a stringent functional coupling of these biological processes in mammals via these cancer signaling pathways, although the underlying biology and mechanisms remain poorly defined.

Our research aims at understanding the molecular and biological processes at the crossroads of cancer metabolism and stem cells. Specifically, we are interested in elucidating the molecular basis how tumor suppression programs control stem cell homeostasis, and how dysregulation of normal stem cell homeostasis contributes to metabolic reprogramming and cancer development. We have been studying these biological questions via exploring the tumor suppressor networks in PI3K pathway, an evolutionarily conserved pathway in the regulation of cancer metabolism, stress resistance and longevity. Principal among these tumor suppressor networks include TSC-mTORC1-directed cell growth machinery, LKB1-mediated energy sensing signaling and the FoxO transcription factors which control stress response and cell survival/proliferation.

Our previous studies, among others, have shown that the FoxO/TSC/LKB1 tumor suppressor network plays critical roles in cancer metabolism and stem cell maintenance. These studies have delineated an intimate link between tumor suppressor pathways that control cancer metabolism and those that regulate stem cell homeostasis, and pointed to the critical importance of coupling energy availability and tissue homeostatic demands. Our future efforts will be aimed at further identifying and characterizing the key components of this tumor suppressor network and other novel tumor suppressors that regulate cancer metabolism, stress response and stem cell biology, as well as decoding the circuits linking fundamental cell biological processes to pathophysiology. We are employing multi-disciplinary approaches, including sophisticated genetic mouse models, integrated transcriptomic/genomic/computational analyses and detailed biochemical mechanistic studies, to dissect these important questions. A deeper understanding of the biological processes linking cancer metabolism to stem cell maintenance will provide novel insight for cancer therapy and regenerative medicine.

Current Lab Members:

Li Zhuang, Hyemin Lee, Zhen-Dong Xiao, Fangyan Dai, Xiaowen Liu, Haineng Xu

Office Address

The University of Texas MD Anderson Cancer Center
Experimental Radiation Oncology
1515 Holcombe Blvd
Unit Number: 0066
Houston, TX 77030-4009
Room Number: Y4.6024
Phone: 713/792-8653
Fax: 713/794-5369
Email: bgan@mdanderson.org

Education & Training

Degree-Granting Education

2006 Cornell University, Ithaca, NY, PHD, Comparative Biomedical Sciences
2000 Fudan University, Shanghai, China, MS, Genetics
1997 Fudan University, Shanghai, China, BS, Microbiology

Postgraduate Training

2010-2011 Instructor, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Ronald DePinho, MD
2006-2010 Postdoctoral Fellow, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, Ronald DePinho, MD

Experience/Service

Academic Appointments

Member, Cancer Biology Program, the University of Texas Graduate School of Biomedical Sciences, Houston, TX, 2/2012-present
Assistant Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2/2012-present

Honors and Awards

2013-2017 Ellison Medical Foundation New Scholar Award, Ellison Medical Foundation
2013-2016 Gabrielle's Angel Foundation Award, Gabrielle's Angel Foundation for Cancer Research
2012-2014 CONquer canCER Now Award, Concern Foundation
2012-2014 CSCDB Faculty Scholar Award, Center for Stem Cell and Developmental Biology, UT MD Anderson Cancer Center
2012-2014 Kimmel Scholar, Sidney Kimmel Foundation
2012-2013 The LAM Foundation Pilot Award, The LAM Foundation
2011-2012 DOD PCRP Exploration - Hypothesis Development Award, Department of Defense
2011 Harvard Chinese Life Science Annual Distinguished Research Award
2010-2014 DOD TSCRP Career Transition Award, Department of Defense
2009-2011 DF/HCC Kidney Cancer SPORE Career Development Award, DF/HCC Kidney Cancer SPORE
2007-2010 Leukemia & Lymphoma Society Fellowship, Leukemia & Lymphoma Society

Professional Memberships

American Association for Cancer Research (AACR)
Active Member, 2006-present
American Society for Cell Biology (ASCB)
Member, 2003-present
The American Association for the Advancement of Science (AAAS)
Member, 2012-present
The Society of Chinese Bioscientists in America (SCBA)
Lifetime memeber, 2012-present

Selected Publications

Peer-Reviewed Original Research Articles

1. 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, 3/15/2014. e-Pub 1/21/2014. PMID: 24448243.
2. 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. e-Pub 8/2013. PMID: 23918370.
3. 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. e-Pub 7/2013. PMID: 23851496.
4. 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. e-Pub 2/2013. PMID: 23444404.
5. Keniry M, Pires MM, Mense S, Lefebvre C, Gan B, Justiano K, Lau YI, 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 & Development 27(8). e-Pub 2013.
6. 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, 4/2012. PMID: 22541435.
7. 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, 3/2/2012. e-Pub 2/16/2012. PMID: 22341455.
8. 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, 2/17/2012. PMCID: PMC3286017.
9. 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, 2/2012. e-Pub 12/2011. PMID: 22147007.
10. 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. PMCID: PMC3143941.
11. 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, 12/2/2010. PMCID: PMC3058342.
12. 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, 5/18/2010. PMCID: PMC2900858.
13. 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. PMCID: PMC3023886.
14. 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. Journal of Biological Chemistry 285(5):3499-3509, 2010. PMCID: PMCPMC2823459.
15. Gan B, DePinho RA. mTORC1 signaling governs hematopoietic stem cell quiescence. Cell Cycle 8(7):1003-6, 4/1/2009. e-Pub 4/2/2009. PMCID: PMC2743144.
16. 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.
17. 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, 12/9/2008. e-Pub 12/3/2008. PMCID: PMC2593615.
18. 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. Molecular and Cellular Biology 28(8):2771-2781, 2008. PMCID: PMCPMC2293096.
19. 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. Journal of Biological Chemistry 282(43):31766, 2007. PMID: 17716968.
20. 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. Journal of Biological Chemistry 281(49):37321-37329, 2006. PMID: 17043358.
21. 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. Journal of Cell Biology 175(1):121-133, 2006. PMCID: PMC2064504.
22. 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. Journal of Bio 281(24):16664-16671, 2006. PMID: 16617055.
23. Wu X, Gan B, Yoo Y, Guan JL. FAK-mediated src phosphorylation of endophilin A2 inhibits endocytosis of MT1-MMP and promotes ECM degradation. Developmental Cell 9(2):185-196, 2005. PMID: 16054026.
24. 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. Journal of Cell Biology 170(3):379-389, 2005. PMCID: PMC2171462.
25. Melkoumian ZK, Peng X, Gan B, Wu X, Guan JL. Mechanism of cell cycle regulation by FIP200 in human breast cancer cells. Cancer Research 65(15):6676-6684, 2005. PMID: 16061648.

Invited Articles

1. Zhang Y, Gan B, Liu D, Paik JH. FoxO family members in cancer. Cancer Biology and Therapy 12(4):253-259, 2011. PMID: 21613825.
2. Gan B, DePinho RA. mTORC1 signaling governs hematopoietic stem cell quiescence. Cell Cycle 8(7):1003-1006, 2009. PMCID: PMC2743144.
3. Gan B, Guan JL. FIP200, a key signaling node to coordinately regulate various cellular processes. Cell Signal 20(5):787-94, 5/2008. e-Pub 11/2007. PMCID: PMC2278039.

Grant & Contract Support

Title: Studying metabolic stress signaling in renal cancer
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 6/1/2014 - 5/30/2019
 
Title: Study the regulation of HSC maintenance and aging by longevity pathways
Funding Source: Ellison Medical Foundation
Role: Principal Investigator
Duration: 9/1/2013 - 8/30/2017
 
Title: Investigating PI3K inhibition-mediated feedback regulation in renal cancer treatment
Funding Source: Cancer Prevention & Research Institute of Texas (CPRIT)
Role: Principal Investigator
Duration: 9/1/2013 - 11/30/2016
 
Title: Study Energy Sensing Signaling in Leukemia Stem Cells and Leukemia Development
Funding Source: Gabrielle's Angel Foundation
Role: Principal Investigator
Duration: 3/1/2013 - 2/28/2016
 
Title: Understanding LKB1 signaling in hematopoietic stem cells
Funding Source: Center for Stem Cell & Development Biiology
Role: Principal Investigator
Duration: 8/1/2012 - 7/31/2014
 
Title: Study the impact of FoxO reactivation on pancreatic treatment
Funding Source: Concern Foundation
Role: Principal Investigator
Duration: 7/1/2012 - 6/30/2014
 
Title: Targeting genetic and metabolic networks in renal cell carcinoma
Funding Source: Sidney Kimmel Founcation
Role: Principal Investigator
Duration: 7/1/2012 - 6/30/2014
 
Title: Understanding the regulation of FoxO by a novel ubiquitin ligase in renal cancer development
Funding Source: UTMDACC Institutional Research Grant (IRG)
Role: Principal Investigator
Duration: 7/1/2012 - 6/30/2013
 
Title: The role of FoxO transcription factors in the molecular pathogenesis of LAM
Funding Source: Lymphangioleiomyomatosis Foundation (LAM)
Role: Principal Investigator
Duration: 1/15/2012 - 1/14/2013
 
Title: ELOVL6, a link between lipid metabolism and prostate cancer development
Funding Source: Department of Defense (DOD)
Role: Principal Investigator
Duration: 2/3/2011 - 12/30/2012
 
Title: TSC-FoxO signaling network in kidney cancer development
Funding Source: DOD/Congressionally Directed Medical Research Programs (DOD/CDMRP)
Role: Principal Investigator
Duration: 8/1/2010 - 7/31/2014

Last updated: 7/26/2014