Craig A. Fletcher, DVM, PhD
My research focuses on (1) the influence of chemokine and chemokine receptor SNPs on inflammation and platelet activation; and (2) determining whether or not chemokines play more of a role in atherogenesis in African Americans than in Caucasians. The central hypothesis is that SNPs in the genes encoding PF4 and Fractalkine and their receptors increase inflammation and thrombosis. In addition, I propose that SNPs in these genes differ between African Americans and Caucasians, and this may account for part of the differential susceptibility to atherosclerotic disease between these two subpopulations. PF4 is a chemokine released from activated platelets, which has potent pro-inflammatory properties. Our hypothesis is that Fractalkine-induced PF4 release is pro-atherogenic. The receptor for PF4 has only very recently been identified as CXCR3B, an isoform of the CXCR3 gene found on endothelium. An important aspect of our research is to identify any polymorphisms that may exist within the CXCR3 gene, and to characterize whether the putative polymorphisms have a functional or pathogenic significance in the context of atherogenesis.
Srivastava K, Cockburn IA, Swaim A, Thompson LE, Tripathi A, Fletcher CA, Shirk EM, Sun H, Kowalska MA, Fox-Talbot K, Sullivan D, Zavala F, Morrell CN. Platelet factor 4 mediates inflammation in experimental cerebral malaria, Cell Host Microbe. 2008 Aug 14;4(2):179-87.
Yamakuchi M, Ferlito M, Morrell CN, Matsushita K, Fletcher CA, Cao W, Lowenstein CJ. Exocytosis of endothelial cells is regulated by N-ethylmaleimide-sensitive factor, Methods Mol Biol. 2008;440:203-15.
Scorpio DG, Ruben DS, Zhaohao, L, Hildreth JE, Fletcher CA, Cervicovaginal evaluation in macaques used as a model for topical microbicide safety studies, Journal of Medical Primatology, 2008 Feb;37 Suppl 1:65-73.
Fletcher CA, and Hildreth JEK, Characterization of an Anti-Lymphocyte Function-Associated Antigen-1 Antibody in Simian Immunodeficiency Virus (SIV)/Pigtail Macaque Model, Comparative Medicine; 2006;56(1):23-30.