Share
PrintYingzi Yang, Ph.D.
B.S. Fudan University, Shanghai, P.R. China, 1988
Ph.D. Cornell University, 1996
(301) 402-2034
(301) 402-2170
49 Convent Dr, MSC 4472
Bethesda, MD 20892-4472
Dr. Yang studies vertebrate embryonic development, with a specific focus on limb and skeletal morphogenesis. Her goal is to understand the mechanisms by which molecular signals are transduced and integrated in a regulatory network to control key events during mammalian embryonic development and adult homeostasis. To that end, her group focuses on the molecular mechanisms of two major families of signaling molecules — Wnt and Hedgehog (Hhs) — in both normal developmental processes and adult diseases, including tumor formation.
In humans and in mice, the 19 members of the Wnt group and the three members of the Hedgehog group are critically important signaling molecules that control cell proliferation and differentiation — processes essential to the developing embryo. Mutations in the genes that code for these molecules can cause devastating birth defects, including debilitating abnormalities of the central nervous system, skeleton, limbs, and many other organs. Disruptions in Wnt and Hedgehog signaling can also promote a variety of cancers. In fact, disrupted Wnt signaling is a leading cause of colon cancer, breast tumors, and brain tumors in adults. Misregulated Wnt and Hedgehog signaling is also involved in bone diseases such as osteoarthritis, osteoporosis and bone tumors.
Skeletal morphogenesis is a typical example of vertebrate organogenesis. It starts from mesenchymal condensation, in which mesenchymal progenitor cells differentiate into either osteoblasts, which form bone, or chondrocytes, which form cartilage, depending on the ossification mechanism. Later, cartilage and bone develop through a precisely coordinated process with the sequential maturation of chondrocytes and osteoblasts and the invasion of blood vessels. Early patterning signals, which include Hhs, Wnts, FGFs, and TGF-superfamily members, provide temporal and spatial information to instruct skeletal anlagen formation, long before overt skeletogenesis. These signaling pathways also play major roles in regulating cell proliferation, differentiation, and organization in the formed skeletal system. Dr. Yang's previous work provided insight into several fundamental aspects of tissue patterning and cell fate determination in the limb and skeletal system. Her current research addresses how signaling pathways exert specific effects in skeletal and other developmental processes, and in stem cell self-renewal/differentiation, and how disruption of these events leads to various diseases and tumors.
To test the function of Wnt and Hedgehog proteins, Dr. Yang's group is using both genetic and biochemical approaches. They have engineered a series of mice with specific genetic mutations that lead to the incorrect expression of specific protein-coding genes. The resulting mouse phenotypes provide powerful clues about a particular protein's function. To understand how these signaling molecules work, Dr. Yang's laboratory cultures cells from mutant and normal animals in vitro, then exposes the cells to particular molecules or growth factors, singly or in combination, to observe the effects. Using these approaches, they seek to understand fundamental events in skeletal morphogenesis, and have made several discoveries in their current research efforts. For example, Dr. Yang has found that different Wnt proteins play distinct roles in regulating chondrocyte differentiation. The canonical Wnt pathway induces synovial joint formation and determines cell differentiation of mesenchymal progenitors by inhibiting chondrogenesis while promoting osteogenesis. This work indicates that the Wnt pathway may be an important diagnostic and therapeutic target for cartilage and bone diseases, such as arthritis and osteoporosis.
Previously, Dr. Yang's laboratory found that non-canonical Wnt5a promotes chondrocyte differentiation by inhibiting canonical Wnt signaling activity. Overactive canonical Wnt signaling is considered a possible cause of some human cancers, particularly colon cancer. Wild-type Wnt5a may, therefore, be a tumor suppressor in adults. In addition, Dr. Yang found that the Hedgehog signaling pathway also plays important roles in postnatal skeletal homeostasis; Wnt5a has also been shown to control vertebrate morphogenesis by regulating cell polarity.
Dr. Yang's group is continuing to study how Wnt and Hedgehog signaling pathways control fundamental aspects of skeletal development and bone diseases. Dr. Yang is also actively investigating the molecular mechanisms underlying the control of cell and tissue organization by the planar cell polarity pathway in embryonic morphogenesis.
Last Reviewed: January 25, 2011
