Dr Yun Fan’s research interest centers on understanding how cell death, cell proliferation, and cell differentiation are coordinated to maintain tissue homeostasis. This has important implications for cancer development and tissue regeneration. As one of our Birmingham Fellows recruited worldwide, he joined us and established his laboratory at Birmingham in 2012.
2005 Ph.D. Biozentrum, University of Basel, Basel, Switzerland
2001 M.S. Sun Yat-sen (Zhongshan) University, Guangzhou, China
1998 B.E. Huazhong University of Science and Technology, Wuhan, China
Dr Yun Fan initially trained as a molecular biologist in China. He then completed his PhD in the field of Neurobiology in Switzerland. He subsequently worked at the University of Texas MD Anderson Cancer Center and the University of Massachusetts Medical School in the United States during which time his research focused on regulation of program cell death (apoptosis) and its related compensatory cell proliferation.
Regulation of apoptosis and compensatory cell proliferation in tissue homeostasis
Tissue homeostasis is the maintenance of normal tissue morphology and function under physiological or pathological conditions. In multi-cellular organisms, this requires coordinated cell death (e.g. apoptosis), cell proliferation, and cell differentiation. On the one hand, in response to stresses such as radiation and accidental injury, cells can get damaged and are removed by a self-destruct mechanism called apoptosis. On the other hand, surprisingly, apoptotic cells can actively induce proliferation of their neighbouring cells to compensate for the cell loss. This phenomenon is termed apoptosis-induced compensatory cell proliferation (apoptosis-induced proliferation). Therefore, both apoptosis and apoptosis-induced proliferation are critical for tissue recovery and organismal survival. Under pathological conditions, mis-regulated apoptosis or apoptosis-induced proliferation can lead to many human diseases including degenerative disorders and cancer. Our research is to investigate the cellular control of apoptosis and apoptosis-induced proliferation, especially how these cellular processes are coordinated and regulated.
Work by us and others has revealed that stress-induced apoptotic cells can send growth signals to trigger compensatory cell proliferation through a non-apoptotic function of caspases, a family of cysteine-proteases that normally execute apoptosis. Intriguingly, we also discovered that apoptosis can induce cell proliferation through distinct mechanisms in different developmental contexts, e.g. in proliferating versus differentiating tissues. However, it is not yet clear how apoptosis-induced proliferation is regulated at the molecular level following activation of caspases, and why distinct mechanisms are employed in a cell context-dependent manner. By taking advantages of Drosophila as a genetically tractable model organism, we have developed unique assays to systematically identify and characterize novel regulators of apoptosis-induced proliferation. Dissecting its underlying regulatory mechanisms will make substantial contributions to our understanding of the cellular strategies and genetic pathways used to maintain tissue homeostasis in response to apoptosis. Our long-term research goal is to elucidate the relevance of apoptosis-induced proliferation in tissue regeneration and tumorigenesis.
2011-2012, Research Assistant Professor, UMass Medical School, Worcester, USA
2009-2011, Instructor, University of Texas MD Anderson Cancer Center, Houston, USA
2006-2009, Postdoctoral Fellow, University of Texas MD Anderson Cancer Center, Houston, USA
Since 2005, Member of the Genetic Society of America
Christiansen A.E., Ding T., Fan Y., Graves H.K., Herz H.M., Lindblad J.L. and Bergmann A. (2012). Non-cell autonomous control of apoptosis by ligand-dependent Hedgehog signaling in Drosophila. Cell Death Differ. doi: 10.1038/cdd.2012.126. http://www.ncbi.nlm.nih.gov/pubmed/23018595
Lee T.V.*, Fan Y.*, Wang S., Srivastava M., Broemer M., Meier P. and Bergmann A. (2011). Drosophila IAP1-mediated ubiquitylation controls processing, but not protein stability, of the initiator caspase DRONC. PLoS Genetics.7 (9): e1002261. (*co-first author)
Fan Y., Lee T., Xu D., Chen Z., Lamblin A.F., Steller H. and Bergmann A. (2010). Dual roles of Drosophila p53 in cell death and cell differentiation. Cell Death Differ.17 (6): 912-921.
Fan Y. and Bergmann A. (2010). The cleaved-Caspase-3 antibody is a marker of Caspase-9-like DRONC activity in Drosophila. Cell Death Differ.17 (3), 534-539.
Xu D., Woodfield S.E., Lee T.V., Fan Y., Antonio C. and Bergmann A. (2009). Genetic control of programmed cell death (apoptosis) in Drosophila. Fly (Austin) 3(1):78-90.
Fan Y. and Bergmann A. (2008). Apoptosis-induced compensatory proliferation. The Cell is dead. Long live the Cell! Trends Cell Biol.18 (10), 467-473.
Fan Y. and Bergmann A. (2008). Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev. Cell14 (3), 339-410. (evaluated by Faculty of 1000 Biology as “Must Read”) http://www.ncbi.nlm.nih.gov/pubmed/18331718