ANDREW S. WEYRICH, Ph.D.

LAB WEBSITE

B.S. 1985, Baldwin-Wallace College
M.S. 1987, Wake Forest University
PhD. 1991, Wake Forest University

RESEARCH:

Our research group includes physician and Ph.D. scientists, graduate and medical students, senior research associates, and research technicians. Our primary research focus is to characterize mechanisms that link thrombosis and inflammation. Our work is relevant to a number of human diseases including atherosclerosis, acute respiratory distress syndrome, cancer, diabetes, and other inflammatory based disorders where thrombosis plays a key role. We use a variety of cell biology and molecular techniques to understand thrombosis and inflammation, exploring questions in primary human cells that include all leukocyte subsets, platelets, and endothelial cells. A variety of cell lines that are more suitable to genetic manipulation are also used as surrogates when required. A primary target of our research is characterizing the expression of inflammatory genes at the post-transcriptional level. This research is rooted from our findings (see select publications, PNAS 95:5556-5561, 1998) that platelets, which are devoid of a nucleus, synthesize proteins in a regulated fashion at the translational level. We have since discovered and characterized novel signaling pathways in platelets that control mRNA translation into protein. Our findings in platelets have also been used as a foundation to study post-transcriptional responses in nucleated cells. In most cases, translation of mRNA to protein is very discrete and adhesion of cells to one another or the extracellular matrix differentially induces the synthesis of distinct gene products. A number of our studies have examined the effect of clinical inhibitors on regulated gene expression and some of our fellows have analyzed the expression of target genes in clinical samples.

SELECT PUBLICATIONS:

Weyrich, A.S., McIntyre, T.M., McEver, R.P., Prescott, S.M., and Zimmerman, G.A. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor- secretion: signal integration and NF- B translocation. J Clin Invest 95:2297-2303, 1995.

Weyrich A.S., Elstad M.R., McEver R.P., McIntyre T.M., Moore K.L., Morrissey J.H., Prescott S.M. and Zimmerman, G.A.: Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 97:1525-1534, 1996.

Weyrich A.S., Dixon D.A., Pabla R., Elstad M.R., McIntyre T.M., Prescott S.M. and Zimmerman G.A.: Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc Natl Acad Sci 95:5556-5561, 1998.

Lindemann S., Tolley N.D., Eyre J., Kraiss L.W., Mahoney T.M., Weyrich A.S. Integrins regulate the intracellular distribution of eIF4E in platelets: a checkpoint for translational control. J Biol Chem, 276:33947-33951, 2001.

Lindemann, S, Tolley, ND, Dixon, DA, McIntyre, TM, Zimmerman, GA, Weyrich, AS. Activated platelets mediate inflammatory signaling by regulated interleukin-1 synthesis. J Cell Biol 154:485-490, 2001.

Galt S., Lindemann S., Allen L., Medd D.J., Falk J.M., McIntyre T.M., Prescott S.M., Kraiss L.W., Zimmerman G.A., Weyrich A.S. Outside-in signals delivered by MMP-1 Regulate Platelet Function. Circ Res, 90:1093-1099, 2002.