 |
Zhenglun Zhu, MD, PhD
Assistant Professor of Medicine, Harvard Medical School
Contact Information:
(617) 732-6593
|
Dr. Jerry Zhu received his M.D. from Beijing Medical University, his Ph.D. from Columbia University and in 2000, completed fellowship training in the Gastroenterology Division at Brigham and Women’s Hospital. The major interest of Dr. Zhu’s research is to understand how signal regulated proteolysis control cell proliferation and differentiation. One of the most fundamental questions facing development biologist is how an organism develops from a fertilized egg that contains a simple symmetrical structure into an adult with three dimensional body plan, the patterning process. Dysregulation of the patterning process results in aborted embryogenesis during early development and frequently results in tumor formation in adult life. Since the biochemical pathways that underlie the patterning process are often reserved thorough life, studying patterning formation during early development has offered an excellent tool to explore the basic mechanisms that underlie the most fundamental questions of development as well as clinical questions, such as the pathogenesis of cancer. Over the past decades, signal regulated- proteolysis as emerged as the central controller of cell cycle progress, signaling transduction, and transcription regulation. Two signaling pathways play important roles in the patterning of early embryos and during gut ontogenesis: the Wnt signaling pathway and the BMP signaling pathways. The signal flux of both pathways is governed by ubiquitin-mediated proteolysis. Altered stability of b-catenin, a downstream transcription regulator of the Wnt signaling, disrupts dorsoventral pattern formation during early embryogenesis and is implicated in the pathogenesis of both sporadic and inherited colorectal cancer. To further define the function of proteolysis during development, we have found that the particular cellular protein degradation machinery that governs signal flow of the Wnt signaling is also involved in toning the effect of signaling of the BMP pathway. Although protein degradations of both Wnt signaling pathways and BMP signaling pathway are phosphorylation dependent, the kinases that control substrate stability of these pathways appear to be different. Current efforts are focused on identifying the kinases involved in regulating protein degradation of the BMP pathway and the extra-cellular signals involved in regulating proteolysis of these pathways. Dr. Zhu is also interested in the study of viral-host interaction. After successfully identifying the receptor and deciphering the intracellular maturation pathway of the Varicella-Zoster virus in a collaborative effort with the lab of Drs. Ann and Michael Gershon of Columbia University, Dr. Zhu’s lab is currently focusing on the mechanism of assembly of HCV, a major liver pathogen that leads to cirrhosis and liver cancer.