Abstract
Autophagy is a highly conserved cellular process for degradation of bulk cytoplasmic materials for maintenance of cellular homeostasis and in response to starvation. Autophagy dysfunction is implicated in a variety of diseases including cancer. Due to its impact on many cellular functions, autophagy has been shown to play both tumor suppressive and tumor promoting functions in different contexts and models. FIP200 (FAK-family Interacting Protein of 200 kDa) was initially identified in the speaker’s laboratory in the 2000s and subsequently shown to be a component of the ULK1/Atg13/FIP200 complex essential for the induction of autophagy. Recent studies by the speaker's group showed that conditional knockout (cKO) of FIP200 decreased mammary tumor development, growth, and metastasis driven by PyMT oncoprotein, thus providing the first evidence for a pro-tumorigenesis role for autophagy in animals with intact immune systems. They also developed an inducible system to delete FIP200 after tumor development in vivo and demonstrated that acute disruption of autophagy by FIP200 deletion in established tumors dramatically blocked their growth. In separate studies, the speaker's lab also reported that ablation of FIP200 results in a progressive loss of neural stem cells (NSCs) pool and impairment in neuronal differentiation specifically in the postnatal brain, but not the embryonic brain. The group further showed that defect in maintaining the postnatal NSC pool was caused by p53-dependent apoptotic responses and cell cycle arrest. However, the impaired neuronal differentiation was rescued by anti-oxidant N-acetyl-cysteine (NAC) treatment, but not by p53 inactivation. In this presentation, the speaker will discuss their latest studies on the analysis of the role of FIP200 and other autophagy genes in the regulation of breast cancer and neural stem cells.
About the speaker
Prof Jun-Lin Guan received his PhD in Biology from the University of California at San Diego in 1987. After postdoctoral training at the Center for Cancer Research at the Massachusetts Institute of Technology, he joined Cornell University faculty as an Assistant Professor in 1991. He rose through the ranks to become a full Professor in 2001. In 2006, he moved to the University of Michigan Medical School as a Professor of Internal Medicine in the Division of Molecular Medicine and Genetics and of Cell and Developmental Biology. In 2014, he joined the University of Cincinnati College of Medicine as the Francis Brunning Endowed Chair and Professor of Cancer Biology, Associate Director for Research of the University of Cincinnati Cancer Institute and Co-leader of Molecular and Cellular Basis of Cancer of the Cincinnati Cancer Center.
Prof Guan’s research centers on the mechanisms of cell signaling in biological processes and how disruption of the normal signaling pathways leads to cancer and other diseases. He has received many awards and honors, including Kuo Mu-Rao Award in 1982, Anna Fuller Cancer Fund fellowship in 1987, SmithKline Beecham Award for Research Excellence at Cornell University in 1993, the Established Investigator Award from American Heart Association in 1998 and League of Research Excellence at University of Michigan Medical School in 2011.
Prof Guan is the author of more than 140 scientific papers, many of which are landmark contributions to his research fields. He has served on the editorial boards of several journals including the Journal of Biological Chemistry, Molecular and Cellular Pharmacology and the Journal of Breast Cancer: Targets and Therapy. He also has been a member of the American Association for Cancer Research and of several National Institutes of Health (NIH) study sections in US. In 2011, he was elected as a fellow of the American Association for the Advancement of Science.
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