Dr. Boyi Gan
The University of Texas MD Anderson Cancer Center
Department of Experimental Radiation Oncology
- Tumor suppressors
- P13K pathway
- Cancer metabolism
- Stem cells
- Kidney Cancer
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.
A tutorial experience in my laboratory would provide an opportunity to learn cancer signaling pathways, cancer metabolism, cancer genetics, and stem cell biology by employing in vitro and in vivo mouse models.
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 2008 Dec 9; 105(49):19384-9. PMCID: PMC2593615
Gan B, DePinho RA. mTORC1 signaling governs hematopoietic stem cell quiescence. Cell Cycle. 2009 Apr 1; 8(7). (invited review) PMCID: PMC2743144
Gan B, Lim C, Chu G, Hua S, Ding Z, Collins M, Hu J, Jiang S, Zhuang L, Chang M, Fletcher-Sananikone E, Zheng H, Wang YA, Kwiatkowski DJ, Kaelin W, Signoretti S, DePinho RA. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell, 2010; 18 (5): 472-84. PMCID: PMC3023886
Gan B, Hu J, Jiang S, Liu Y, Ergun S, Zhuang L, Fletcher-Sananikone E, Colla S, Wang YA, Chin L, DePinho RA. LKB1 regulates quiescence and metabolic homeostasis of hematopoietic stem cells. Nature. 2010; 468: 701-704. PMCID: PMC3058342