More about
Dr. Chen:

Dr. Chen 101
(for non-scientists)

Dr. Chen's CV in
brief

Publications

Cardiovascular Biology Research Program

Dr. Chen In The News

New discovery points to genetic roots of prostate cancer

Hong Chen, Ph.D. Assistant Member, Cardiovascular Biology Research Program

Research Interests
Endocytosis is a fundamental mechanism used by cells to communicate with the environment. It is critical for antigen presentation, nutrient uptake, lipid membrane exchange and receptor internalization. Endocytosis of activated receptors can regulate many cellular events including signal transduction, and malfunctions in endocytosis can contribute to pathological conditions leading to a variety of illnesses. Among these are cardiovascular disease, diabetes, cancer and neurological disorders, highlighting its central role in maintaining cellular homeostasis.

We previously showed that epsins are a founding family of endocytic adaptor proteins required for internalization and degradation of ubiquitinated receptors. More recently, we showed that deletion of epsins 1 and 2 increases VEGF signaling in endothelial cells, and inhibits Notch signaling in developing embryos, suggesting a potential regulatory role. Thus, the research in the lab centers on exploring how epsin-mediated endocytosis regulates receptor signaling in vitro and how this regulation controls physiological and pathological consequences in vivo. In particular, we are interested in studying the following three research areas:

The first research theme is to determine how epsin-mediated endocytosis of VEGFR-2 affects VEGF signaling and modulates angiogenesis both physiologically and pathologically. We have generated mutant mice that lack epsin 1 and 2 globally or selectively in endothelial cells. We will utilize endothelial cell-specific epsin double-knockout mice to determine the function of epsins in regulating angiogenic sprouting, endothelial cell proliferation, and endothelial cell survival. We also seek to define the molecular mechanism underlying the regulation of VEGF signaling by epsin-mediated endocytosis.

Secondly, we are investigating how epsin-mediated endocytosis of Notch ligand, Dll4, activates Notch signaling and consequently regulates embryonic angiogenesis, including arterial-venous differentiation. We plan to use endothelial cell-specific, epsin double-knockout mice to assess Notch signaling defect and abnormal embryonic angiogenesis.

Our third research theme centers on probing the role of epsin-mediated endocytosis of other receptors important for vascular development and angiogenic remodeling. Examples include angiopoietins (Ang1 and Ang2) and their cognate receptors (Tie2 and Tie1) and platelet-derived growth factor β (PDGFβ) and its receptors. Furthermore, epsin knockout mouse models are ideally suited for identification of novel factors involved in tumor angiogenesis and identification of new vascular targets for drugs that inhibit tumor growth and treat a range of vascular diseases.

Joined OMRF Scientific Staff in 2008.

Mailing Address
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-2750, 12755
Fax:
E-mail: Hong-Chen@omrf.org