William Van Nostrand, Ph.D. (Professor)
Ph.D., Biochemistry, University of California, 1985
We are interested in understanding the role of amyloid ß-protein precursor (AßPP) and its derived fragment Aß in the cerebrovascular pathology found in Alzheimer’s disease and related disorders. Our research focuses on pathogenic interactions of Aß with cells in cerebral blood vessels that lead to cellular degeneration, loss of vessel wall integrity, and hemorrhagic stroke.
Our studies in this area are multi-leveled involving basic protein-protein interactions, in vitro cerebrovascular cell culture models, and several in vivo transgenic mouse models recently developed in the laboratory. In addition, we have a strong interest in physiologic functions of AßPP in regulating hemostatic mechanisms. To this end we utilize in vitro systems and several in vivo mouse gene knockout and transgenic models to elucidate the role of AßPP in vascular processes involved in coagulation, stroke, and traumatic brain injury.
- Melchor, J.P. and Van Nostrand, W.E. (2000) Fibrillar Amyloid ß-Protein
Mediates the Pathologic Accumulation of its Precursor in Cerebrovascular Smooth
Muscle Cells. J. Biol. Chem. 275:9782-9791.
- Wagner, M.R., Keane, D.M., Melchor, J.P., Auspaker, K.R., and Van Nostrand.
W.E. (2000) Fibrillar Amyloid ß-Protein Binds Protease Nexin-2/Amyloid
ß-Protein Precursor: Stimulation of its Inhibition of Coagulation Factor
XIa. Biochemistry 39:7420-7427.
- Van Nostrand, W.E., Melchor, J.P., Keane, D.M., Saporito-Irwin, S.M.,
Romanov, G. Xu, F. and Davis, J. (2002) Localization of a Fibrillar Amyloid
ß-Protein Binding Domain on its Precursor. J. Biol. Chem. 277:36392-36398.
- Jung, S.S., Zhang, W., and Van Nostrand, W.E. (2003) Pathogenic Aß
Induces the Expression and Activation of Matrix Metalloproteinase-2 in Human
Cerebrovascular Smooth Muscle Cells. J. Neurochem. 85:1208-1215.
- Davis, J., Wagner, M.R., Zhang, W., Xu, F., and Van Nostrand, W.E..
Amyloid ß-Protein Stimulates the Expression of Urokinase-type Plasminogen
Activator (uPA) and its Receptor (uPAR) in Human Cerebrovascular Smooth Muscle
Cells. (2003) J. Biol. Chem. 278:19054-19061.