CCBIO Special Seminar – Hong Chen
Speaker for this CCBIO Special Seminar: Hong Chen, Principal Investigator and Research Associate at Vascular Biology Program in Boston Children’s Hospital and Associate Professor in Harvard Medical School. Title: “Endocytic Adaptor Protein Epsin is a Gatekeeper of the Quiescent Endothelium.” Due to the Covid-19 circumstences, the seminar will be held through a digital platform (Zoom Webinar), so you can attend even from the comfort of your own home.
Speaker: Hong Chen, Principal Investigator and Research Associate at Vascular Biology Program in Boston Children’s Hospital and Associate Professor in Harvard Medical School.
Title: “Endocytic Adaptor Protein Epsin is a Gatekeeper of the Quiescent Endothelium”
Time: September 28 at 14.30.
Place: Webinar through Zoom.
Link to join Webinar: https://uib.zoom.us/j/64020660783?pwd=ZGZ1MmVlU0hYL2l1M3d0WXppZWlaQT09
Webinar ID: 640 2066 0783
Webinar Passcode: w7FtpsSB
Chair: Reidunn Edelmann
Impeding pathological angiogenesis associated with vascular disorders is paramount in treating disabling and deadly diseases such as blindness, diabetes and cancer. Epsins are a family of prominent endocytic adaptor proteins. We show that epsins, via their ubiquitin-interacting motifs (UIM), are critical for activated VEGFR2 internalization and degradation and VEGF signaling attenuation. Intriguingly, endocytosis of VEGFR2 via a different endocytic adaptor protein, Dab2, results in enhanced VEGF signaling. We show that epsins and Dab2 competitively interact with VEGFR2 via a mutually exclusive mechanism. Consequently, mice lacking epsins and Dab2 reduce heightened angiogenesis in epsin mutants and restore attenuated angiogenesis in Dab2 mutants. However, whether the antagonism of epsins and Dab2 is governed by upstream signals is poorly understood. Our latest study revealed that Sphingosine 1 Phosphate (S1P) enhances epsins while reduces Dab2 binding to VEGFR2 to potentiate VEGFR2 degradation, implicating that S1P may be one of long-sought-after upstream cues that triggers epsin-mediated downregulation of VEGF signaling. Given that VEGF signaling plays a central role in normal, as well as pathological angiogenesis, our work to discover new molecules and pathways, in particular, upstream signals and genetic modifiers that reign epsins’ activity in regulating VEGF signaling and pathological angiogenesis paves the way to develop new therapeutic approaches for the prevention and treatment of cardiovascular and other diseases.
Hong Chen is a Principal Investigator and Research Associate at Vascular Biology Program in Boston Children’s Hospital and Associate Professor in Harvard Medical School. She was an Associate Member in Cardiovascular Biology at Oklahoma Medical Research Foundation, and Associate Professor in University of Oklahoma Health Sciences Center. She received her 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. She 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). Her group developed a novel conditional epsin 1fl/fl; epsin 2-/- mouse, which has been pivotal to the group's continuous success by allowing characterization of the spatial and temporal roles of epsins. Using this approach, they 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). They 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 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). Chen has 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. Her group is 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. They will use novel genetic manipulated animal models to characterize the molecular mechanisms underlying diseased processes and interrogate fundamental problems.
All interested researchers, students and others are welcome!