Wang  Min, Ph.D.

Training:

1980-84 B.S. (Biology), Wuhan University, China.
1984-89 Graduate student (Cell Biology), Shanghai Institute of Cell Biology, Chinese Academy of Sciences.
1989-993 Ph.D. (Molecular Biology and Genetics), University of Wales, Swansea U.K.
1993-1995 Postdoctoral Associate with Dr. Peter Lengyel, Dept. of Molecular Biophysics and Biochemistry, Yale University.
1995-1997 Postdoctoral Fellow with Dr. Jordan S. Pober, Dept. of Pathology and Immunology, Yale University School of Medicine.

Expertise:

Cytokine signaling; angiogenesis; Biology of vascular endothelium; gene therapy.

Research Interests:

Myocardial infarction due to atherosclerosis of coronary arteries remains the leading cause of death in the United States. Excessive/chronic inflammatory responses (e.g., TNF) and increases in reactive oxygen species (ROS) represent common pathogenic mechanism for atherosclerosis. The vascular cell that primarily limits the inflammatory and atherosclerotic process is the vascular endothelial cells (EC). Inflammation/ROS induces EC dysfunction by disturbing normal homeostasis, relaxation and survival. These defects in EC function are mediated by cytokine/redox-regulated signal transduction and gene transcription. The primary goal in my laboratory is to dissect signal pathways during inflammatory responses and develop therapeutic targets for treatment of vascular diseases. We have focused on the following areas of inflammation: 1. To dissect TNF signaling pathways in EC. 2. To understand how shear stress inhibits TNF signaling to function as an atheroprotective factor. 3. To define the role of inflammation/oxidative stress in vascular diseases including atherosclerosis, graft arteriosclerosis, insulin resistance, and cardiomyopathy/heart failure. 4. To determine the mechanism of inflammation/ischemia-induced angiogenesis/arteriogenesis and vascular remodeling. In the first two areas, we have focused on apoptosis signal-regulating kinase (ASK1), a member of MAP3Ks mediating stress-activated kinase (JNK/p38) cascades. We have elucidated the mechanisms for ASK1 activation by various stresses (TNF, ROS and DNA damaging agents). Moreover, ASK1 is a target of laminar flow. While TNF/ROS activates ASK1, atheroprotective laminar flow inhibits ASK1 and ASK1-induced EC activation and apoptosis. We are now identifying signal transducers mediating the function of shear stress. We have recent identified new protein AIP1, a new member of Ras-GAP family protein, is a potential candidate. In the third area, we have shown that inflammation-induced mitochondria dysfunction (ROS generation) and intracellular kinase cascades play critical roles in causing EC dysfunction characterized by reduction of nitric oxide (NO) bioavailability, insulin sensitivity and EC survival. However, cellular anti-oxidant thioredoxin proteins (particularly the mitochondrial form) are critical regulators of inflammation/oxidative stress in EC. In the fourth area, we have demonstrated that antiangiogenic gene therapy inhibits progression of angiogenesis-dependent diseases such as cancer and rheumatoid arthritis in animal models. We have further identified TNFR2-Bmx-VEGFR2-mediated angiogenic pathway plays a critical role in inflammation/ischemic-induced angiogenesis/arteriogenesis and tumor metastases.

Professional Service:

1984-89 Chinese Biochemical Society
1989-92 British Biochemical Society
1990-92 British Genetics Society
1993 American Association for the Advancement of Science (AAAS)
1999 American Association of Cancer Research (AACR)
1999 North American Vascular Biology Organization (NAVBO)
2000 American Heart Association (AHA)

Selected Publications: