Wentian YangAssociate Professor of Medicine, Associate Professor of Orthopaedics
Dr. Yang received his M.D. from Lanzhou University School of Medicine and a Ph.D. in Molecular Biology from Sichuan University School of Medicine in China. He completed his post-doctoral training in the field of cellular signal transduction and cancr biology with Dr. Benjamin G. Neel at Harvard Medical School. Currently, Dr. Yang is appointed as an associate professor of Orthopaedics and Medicine at the department of Orthopaedics of Brown Alpert Medical School.
Dr. Yang studies the regulation of development and homeostasis of bone and cartilage by protein tyrosine kinases (PTK) and phosphatases (PTP). One direction of his research focuses on how the viability, proliferation and chondrocytic differentiation of cartilage stem cells/progenitors are modulated by PTK and PTP. He also has a research interest in cellular signaling pathways that control the differentiation and function of osteoclasts and bone mineral homeostasis.
Musculoskeletal disorders and diseases that cause cartilage degeneration or bone mineral loss remain the leading cause of disability, significantly affecting the quality of life. At the cellular level, three types of cells are primarily responsible for building and maintaining healthy bone and cartilage, which are osteoblasts (OB), chondrocytes and osteoclasts (OC). Understanding the molecular and cellular mechanisms by which the development and homeostasis of OB, chondrocytes and OC are regulated will lay a new foundation on which novel therapeutics could be developed to prevent and/or treat skeletal disorders.
It is well known that protein tyrosine kinase (PTK) signaling is critical in regulation of chondrogenesis. In contrast, little is known about the role of protein tyrosine phosphatases (PTP) in this context. SHP2, encoded by the PTPN11 gene, is one of two vertebrate Src homology-2 domain containing PTP. SHP2 is ubiquitously expressed and its loss-of-function mutations were recently linked to human cartilage tumor syndrome metachondromatosis, implicating an important role for SHP2 in cartilage development and homeostasis. In a recent study aimed at characterizing the skeletal phenotype of mice lacking Shp2 in chondroid cells at various developmental stages, we identified a novel population of Ctsk-expressing chondroid progenitors (CCP) in joints; Shp2 was shown to negatively regulate the proliferation and chondrocytic terminal differentiation of CCP and osteochondroprogenitors. Currently we are investigating the molecular and cellular mechanisms by which SHP2 modulates chondrogenesis and cartilage homeostasis.
Osteoclasts (OC) are the exclusive bone resorbing cells in mammals, playing a central role in the formation of skeleton and regulation of bone mass. Dysregulation of the development and function of OC is linked to several skeletal diseases, such as osteoporosis, osteopetrosis and periprosthetic osteolysis, significantly affecting the quality of life. OC originate from hematopoietic cells, their differentiation along OC lineage requires the cellular signaling initiated by two key growth factors: macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). Another direction of our research is to understand how osteoclastogenesis is regulated by M-CSF and RANKL-evoked signaling cascades. By using genetic loss-of-function approaches and other biochemical means, we recently identified Shp2 as a key regulator downstream RANK to promote the expression of nuclear factor of activated T cells (NFATc1) and the fusion of preosteoclasts; inhibition of this signaling pathway can compromise mature osteoclast formation and reduce bone mineral loss. We are fascinated by these findings and expect that the outcome of these studies would add a new dimension regarding the prevention and treatment of periprosthetic osteolysis and osteoporosis.
NIH/NIAMS RO1AR066746 Yang (PI) 09/15-08/20
"Role of PTPN11 in Cartilage Stem Cells and Tumorigenesis" The major goal of this study is to understand the biology of Ctsk+ cartilage stem cells and the regulatory role of PTPN11 in cartilage.
NIH/NIGMS 1P20 RR025179 7/09-7/14
"Stem Cell Biology: New Directions in Clinical and Basic Research" Project III (PI: Yang): SHP2 in Hematopoietic Stem Cell Property Maintenance. The major goal of this project is to understand how Shp2 regulates hematopoietic and cartilage stem cell self-renewal and differentiation.
NIH R21AR057156 Yang (PI) 10/09-9/12
"SHP2 in Osteoclastogenesis and Bone Remodeling" The major goal of this project is to understand the biological and biochemical role of Shp2 in osteoclast development and function.
Arthritis National Research Foundation (ANRF) Yang (PI) 07/14-06/16
The Ethelmae Haldan Grant for Innovative Science in Osteoarthritis: "Role of Cathepsin K+ Chondroid Progenitors in Articular Cartilage Anti-degeneration" The goal of this study is to determine the role of Ctsk+ chondroprogenitors in maintaining articular cartilage homeostasis.
Brown University Alpert Medical School Dean's Award Yang (PI) 07/15-06/16
"Targeting the SHP2 Signaling Pathway to Ameliorate Bone Mineral Loss" The goal of this project is to understand how SHP2 regulates genome-wide expression of osteoclastogenic genes and whether SHP2 pathway inhibition ameliorates osteolcast-mediated bone resorption.
American Society of Hematology since 1996
Orthopaedic Research Society since 2007
American Society of Bone and Mineral Research 2009
International Society of Microvesicle Research 2010
International Chinese Hard Tissue Association 2007