Assistant Professor of Molecular Microbiology & Immunology (Research)
Division of Biology and Medicine, Brown University
Sidney Frank Hall, Room 258
Box G-B5, 185 Meeting Street
Providence, RI 02912
Yang Zhou, PhD
Yang Zhou, PhD is currently an Assistant Professor of Molecular Microbiology & Immunology (Research) at Warren Alpert Medical School of Brown University. He is the Principal Investigator of a 5 month pilot project with the CPVB COBRE entitled: Chitinase 3-like-1 in Pulmonary Hypertension Associated with Interstitial Lung Disease.
Dr. Zhou is a graduate of Nanjing University, Nanjing, China and University of Texas Health Science Center, Houston TX where he received his PhD in Biochemistry and Molecular Biology.
Dr. Zhou’s primary research interests are directed towards understanding the immunopathogenesis of lung injury and repair. I have interrogated the roles of a chitinase-like protein and its receptors in a variety of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. My future research plans are aimed at dissecting the common mechanisms that underlie the pathogenesis of pulmonary fibrosis, specifically the role of intracellular receptor trafficking pathways in disease progress. My long-range research goals are to identify the immune and cellular responses that mediate lung injury and repair responses and to identify specific molecular targets that can be targeted in the treatment of related disorders.
Chitinase 3-like-1 in Pulmonary Hypertension Associated with Interstitial Lung Disease
Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease (ILD). Despite considerable efforts to understand the disease pathogenesis, the mechanisms that drive the vascular remodeling responses in the lung are poorly understood.
Chitinase 3-like-1 (CHI3L1), also called YKL-40 in humans and BRP-39 in mice, is a prototypic chitinase-like protein belonging to the 18 glycosyl hydrolase gene family. It is produced by a variety of cells including macrophages, epithelial cells, and fibroblasts. It can be readily detected in the circulation of normal individuals and is greatly dysregulated in the circulation and/or tissues from patients with a variety of diseases characterized by inflammation and/or tissue remodeling, and in ILD is known to predict clinical decline. Studies from our laboratory demonstrated that CHI3L1 plays a protective role in lung injury but pro-fibrotic roles during the repair process of the lung. In addition, increased plasma CHI3L1 is associated with endothelial dysfunction in obstructive sleep apnea. However, despite its importance as a regulator of injury/repair responses in multiple tissues, the interrelationship between CHI3L1 and vascular remodeling has never been investigated in the context of pulmonary hypertension secondary to ILD. Our preliminary studies identified that CHI3L1 has at least two cell surface receptors, IL-13Rα2 and CRTH2. We hypothesize that CHI3L1 contributes to the development of pulmonary hypertension associated with ILD through stimulation of pulmonary vascular remodeling. The hypothesis will be tested in the following two aims:
Aim #1: Determine whether the genetic ablation and/or transgenic overexpression of CHI3L1 alter the pathogenesis of pulmonary hypertension in a mouse model of ILD.
Aim #2: Determine the CHI3L1 receptor responsible for the altered pathogenesis of pulmonary hypertension in a mouse model of ILD.
Jack A. Elias
Dean of Medicine and Biological Sciences
Frank L. Day
Professor of Biology, Professor of Molecular Microbiology and Immunology, Professor of Molecular Biology, Cell Biology and Biochemistry, Professor of Medicine
Alpert Medical School of Brown University