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Gen-sheng Feng


Molecular Signaling in Cancer, Metabolism and Stem Cells

At the heart of cancer research is the elucidation of oncogenes and tumor suppressor genes (or anti-oncogenes), which has been a driving force in the cancer field for several decades. Most recent studies in this and other labs have revealed dual roles of genes in promoting and suppressing hepatocellular carcinoma (HCC). Deciphering the “paradoxical” effects of these genes may provide a fresh view on the fundamental mechanisms of carcinogenesis, which can lead to development of mechanism-based therapeutics for HCC. Our current focuses are on delineating genetic and epigenetic interactions and cell-cell communications that drive hepatocarcinogenesis. We are very interested in isolating and characterizing cancer stem cells, CSCs (or tumor-initiating cells, TICs) in the liver, and in dissecting the dynamic interplay between tumors and the hepatic microenvironment. Efforts are also being devoted to elucidation of metabolic changes in tumor cells and to search of biomarkers for early diagnosis of liver cancers.

We are also interested in deciphering the common and distinct biochemical pathways in self-renewal of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs), with the objective of understanding how an HSC pool is maintained throughout life, and with the ultimate goal of identifying novel targets for elimination of LSCs.

Another focus is on dissecting the signaling events involved in metabolic disorders such as obesity and diabetes. Ongoing experiments are aimed at understanding the intertwining of leptin and estrogen signaling cascades, to illustrate why estrogen has a leptin-like effect in control of metabolism, why postmenopausal women have the tendency to develop obesity, and why obesity promotes breast cancer. Whereas obesity has become a serious health problem in developed countries worldwide, one ongoing project in the lab is to investigate an indispensable physiological role of adipogenesis and adipose tissue in mammals, as revealed by the most recent data obtained in this lab.

Select Publications

  • Y Liang, K Kaneko, B Xin, J Lee, X Sun, K Zhang and GS Feng. Temporal analysis of postnatal liver development and maturation by single cell transcriptomics. Developmental Cell. In press, 2022
  • WS Chen, Y Liang, M Zong, JJ Liu, K Kaneko, KL Hanley, K Zhang and GS Feng. Single-cell transcriptomics reveals opposing roles of Shp2 in Myc-driven liver tumor cells and microenvironment. Cell Reports 37(6), P109974, 2021
  • KL Hanley, Y Liang, G Wang, X Lin, M Yang, M Karin, W Fu and GS Feng. Concurrent Disruption of Ras/MAPK and NF-kB Pathways Induces Circadian Dysregulation and Hepatocarcinogenesis. Mol Cancer Res, Online, Nov 22, 2021
  • B Xin, M Yang, P Wu, L Du, HX Deng, E Hui and GS Feng. Enhancing the therapeutic efficacy of PD-L1 antibody for metastasized liver cancer by overcoming hepatic immunotolerance. Hepatology 2021, Accession Number: 34860431.
  • G Wang, X Luo, Y Liang, K Kaneko, H Li, XD Fu and GS Feng. A tumorigenic index for quantitative analysis of liver cancer initiation and progression. PNAS 116, 26873-26880, 2019.
  • L Wen, B Xin, P Wu, CH Lin, C Peng, G Wang, J Lee, LF Lu and GS Feng. (2019). An Efficient Combination Immunotherapy for Primary Liver Cancer by Harmonized Activation of Innate and Adaptive Immunity. Hepatology 69, 2518-2532, 2019.
  • Jin L, R Liao, G Wang, BH Yang, X Luo, NM Varki, SJ Qiu, B Ren, W Fu, and GS Feng. Preventive inhibition of liver tumorigenesis by systematic modulation of innate immunity. Cell Reports, 21, 1870-1882, 2017.
  • Li S, DDF Hsu, B Li, X Luo, N Alderson, L Qiao, L Ma, HH Zhu, Z He, K Suino-Powell, K Ji, J Li, J Shao, HE Xu, T Li and GS Feng. Cytoplasmic tyrosine phosphatase Shp2 coordinates hepatic regulation of bile acid and FGF15/19 signaling to repress bile acid synthesis. Cell Metabolism 20, 320-332, 2014.
  • Feng GS. Conflicting roles of molecules in hepatocarcinogenesis: paradigm or paradox (Invited Review). Cancer Cell 21, 150-154, 2012.
  • EA Bard-Chapeau, S Li, J Ding, SS Zhang, HH Zhu, F Princen, DD Fang, T Han, B Bailly-Maitre, V Poli, NM Varki, H Wang and GS Feng. PTPN11/Shp2 acts as a tumor suppressor in hepatocellular carcinogenesis. Cancer Cell 19, 629-639, 2011.


Dr. Feng received his PhD degree at Indiana University Bloomington and did a postdoctoral fellowship at the University of Toronto.

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