Zeng
Huiyan . Zeng, Ph.D.
Instructor of Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN-270F
Boston, MA 02215
Office Phone: 617-667-2329
Office Fax: 617-667-3591
Email:
hzeng@bidmc.harvard.edu


Education/Training/Appointments:

Huiyan Zeng earned her Ph.D. in Division of Molecular Medicine, Department of Pharmacology, Boston University Medical Center, MA in 1998. She performed Postdoctoral training / NIH/NCI Postdoctoral fellowship (NRSA) at Beth Israel Deaconess Medical Center / Harvard Medical School with Dr. Debabrata Mukhopadhyay. In 2002, Dr. Zeng was appointed as an Instructor in Department of Pathology, Beth Israel Deaconess Medical Center / Harvard Medical School and obtained her NIH/NCI career development award. Later, she became an Assistant professor.


Research Interests: Molecular mechanism and signaling pathways in pathological angiogenesis

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Basic Research - The research in my laboratory focuses on the molecular mechanism and signaling pathways to identify therapeutic target for pathological angiogenesis.

Great success has been achieved in cancer treatment, however, cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effect. There is a need to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. We identified orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target and Down Syndrome Candidate Region 1 (Aliases: DSCR1, ADAPT78, CSP1, DSC1, MCIP1, RCN1) are such targets.

Growth of tumors and angiogenesis induced by VEGF-A, histamine, and serotonin are almost completely inhibited in Nur77 knockout mice. However, Nur77 null mice are viable and fertile, can develop an apparently normal adult vasculature, and have no defects in normal skin wound healing. Angiogenesis and normal skin wound healing are greatly induced and improved in our EC-Nur77-S transgenic mice, in which Nur77 full length cDNA is specifically and inducibly expressed in the mouse endothelium. The transgenic mice are healthy after Nur77 has been induced for three months. TR3 is required for pathological angiogenesis, but is not essential for developmental and physiological angiogenesis, rendering it a potentially attractive target for pro- and anti-angiogenic therapies.

Currently, our projects are 1) to study the molecular mechanisms, by which TR3/Nur77 and DSCR1-1L regulates angiogenesis and their function in tumor growth, inflammation and skin wound healing; 2) the signaling pathways that regulates the expression of TR3/Nur77 and DSCR1-1L; and 3)Identify the therapeutic reagents that target TR3/Nur77 and DSCR1-1L for tumor, inflammation and skin wound.


New and Noteworthy Publications:

Niu G, Ye T, Qin LL, Bourbon PM, Chang C, Zhao S, Li Y, Zhou L, Cui P, Rabinovitz I, Mercurio AM, Zhao D, Zeng H. . Orphan nuclear receptor TR3/Nur77 improves wound healing by up-regulating the expression of integrin beta4. FASEB J. 2015 Jan;29(1):131-40..

Zhao S, Zhou L, Niu G, Li Y, Zhao D, Zeng H. . Differential regulation of orphan nuclear receptor TR3 transcript variants by novel vascular growth factor signaling pathways. FASEB J. 2014 Oct;28(10):4524-33..

Qin L, Zhao D, Xu J, Ren X, Terwilliger EF, Parangi S, Lawler J, Dvorak HF, Zeng H. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1. BLOOD 2013 Mar 14;121(11):2154-64.

Zhao D, Qin L, Bourbon PM, James L, Dvorak HF, Zeng H. Orphan nuclear transcription factor TR3/Nur77 regulates microvessel permeability by targeting endothelial nitric oxide synthase and destabilizing endothelial junctions. Proc Natl Acad Sci U S A. 2011 Jul 19; 108(29):12066-71. (PNAS direct submission).

$Zeng H, Qin LL, Zhao D, Tan X, Manseau EJ, Hoang MV, Senger DR, Brown LF, Nagy JA, Dvorak HD. Orphan Nuclear Receptor TR3/Nur77 regulates the early steps of VEGF-A-induced angiogenesis through its transcriptional activity. J Exp Med. 2006, 203: 719-729 ($Corresponding author).

Qin LL, Zhao D, Liu L, Nagy JA, Hoang MV, Brown LF, Dvorak HF, Zeng H. Down Syndrome Candidate Region 1 Isoform 1 (DSCR1-1L)-mediates angiogenesis through the Calcineurin-NFAT pathway. Mol Cancer Res. 2006, 4, 811-820.

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