William D. Wagner, PhD, FAHA
William D. Wagner, Ph.D., FAHA, Professor
Dr. William Wagner was born in Pennsylvania and received his M.S. degree in Physiology and Biochemistry from West Virginia University. He was a National Science Teaching Fellow and an NIH Research Fellow in Pathobiology. He is currently a Professor of Pathology, Wake Forest School of Medicine, and an Associate in the Wake Forest Institute for Regenerative Medicine. He serves on various NIH and American Heart Association committees and review programs and has over 180 publications.
SYNOPSIS OF AREA OF INTEREST: Cell-cell and cell-matrix interactions; cell growth; structure/function/regulation of proteoglycans and collagen; tissue repair.
DETAILED AREA OF INTEREST: Communication systems of cells rely on interactions of macromolecules present on the cell surface or in the intercellular matrix. A family of molecules, the syndecans, participates in this process and act in a number of ways to regulate cell activities and functions. Some examples include: 1) the inhibition of cell proliferation by heparan sulfate of syndecan-4 through gene regulation, 2) cell/cell interaction through syndecan 1, and 3) facilitation of fibronectin interaction with cells through syndecan/integrin receptor cooperativity. In order to understand how macromolecular interactions influence normal and pathologic processes in cells and tissues, current research is directed toward understanding the genetic regulation of syndecan genes and structural heterogeneity of the heparan sulfate moiety of the syndecans.
Ferritin is the primary intracellular iron-binding protein that limits free iron availability, and as such, is a critical mediator of cellular protection against free radical injury. Dr. Torti's laboratory has demonstrated the molecular details of the regulation of ferritin by inflammatory cytokines such as tumor necrosis factor (TNF) and IL-1 (interleukin-1). His lab has also elucidated the molecular basis of the ferritin regulation by pro-oxidant stress, including that induced by environmental toxins. The cellular and organismal consequences of ferritin dysregulation for cancer development are also areas of active research in Dr. Torti's laboratory.
The field of chemoprevention is closely associated with iron biology. Chemopreventive agents target chemopreventive ferritin genes as well as other antioxidant response genes. The ability of oncogenes to perturb this process, such as Myc and EIA, are other areas of active laboratory investigation and suggest that the transformed phenotype harnesses and modifies cellular iron levels to enable vigorous cell growth and proliferation. Not only is ferritin important at a cellular and tissue level, but epidemiologic studies suggest the risk of developing cancer (as well as heart and neurodegenerative diseases) is increased in patients with high iron burdens. What fundamental biological mechanisms underlie this observation? Can the use of genetic testing for individual variation in levels of ferritin and other proteins of iron metabolism predict for cancer susceptibility? How does genetic variation link to environmental and dietary exposures? These are areas of active collaborations of the Torti lab and other laboratories at Wake Forest University.