I am a Principal Investigator and Research Associate at Vascular Biology Program in Boston Children’s Hospital and Associate Professor in Harvard Medical School. I was an Associate Member in Cardiovascular Biology at Oklahoma Medical Research Foundation, and Associate Professor in University of Oklahoma Health Sciences Center. I received my PhD from Yale University and completed postdoctoral training with Pietro DeCamilli, a premier cell biologist in the Howard Hughes Medical Institute at Yale Medical School. I was the first to discover a family of important endocytic adaptor proteins, epsins (Chen et al., Nature, 1998, Chen et al., Proc. Natl. Acad. Sci. USA, 2003, 2005 and 2009). My group developed a novel conditional epsin 1fl/fl; epsin 2-/- mouse, which has been pivotal to our continuous success by allowing characterization of the spatial and temporal roles of epsins. Using this approach, we elegantly revealed a novel function of endothelial cell-specific or lymphatic endothelial cell-specific epsins in the specific regulation of VEGF signaling through controlling the internalization and degradation of its respective VEGFR2 or VEGFR3 receptor. Epsin loss dramatically impaired VEGFR2 and VEGFR3 downregulation resulting in the development of dilated and dysfunctional blood and lymphatic vascular networks (Pasula, et al. JCI, 2012; Tessneer, et al. ATVB, 2014; Liu, et al. Science Signaling, 2014, Dong, et al. JCI, In Press, Rahman, et al. Circulation Research, Revision).

Fascinatingly, we have also uncovered a positive correlation between cancer severity and elevated epsins expression in human cancer patients. Importantly, elevated epsin expression is specific to the tumor cells thus implicating a tumor intrinsic role for epsins in the development and progression of cancer. Methodical in vivo and in vitro analyses of these epsin deficient models allowed us to delineate oncogenic roles for epsins in cancer development and progression, which are completely independent of its classically defined endocytic adaptor function (Chang, et al. Nature Communications, 2015; Cai, et al. Cancer Cell Revision). We have also embarked on studies to identify and characterize the mechanistic roles of endothelia cell-specific and macrophage-specific epsins through the creation of epsin-depleted genetically manipulated mouse models on ApoE-/- and LDLR-/- background. We are very well positioned to unveil novel therapeutic targets that can promote angiogenic and lymphatic regeneration to correct defective angiogenesis and lymphangiogenesis, suppress undesired inflammation to treat obesity, and retard cancer initiation and progression. We will use novel genetic manipulated animal models to characterize the molecular mechanisms underlying diseased processes and interrogate fundamental problems.