Kirkwood A. Pritchard Jr., Ph.D.
Professor, Surgery, Pharmacology & Toxicology
Vice Chair Research, Surgery
Chair, Research Affairs Committee
Director, Translational Vascular Biology Program
My laboratory investigates basic mechanisms of vascular and pulmonary inflammation in a variety of disease states. We were the first to demonstrate that atherogenic concentrations of low-density lipoprotein (LDL) uncoupled endothelial nitric oxide synthase (eNOS) activity, which converts eNOS from an •NO synthase into an NADPH oxidase in cultured endothelial cells. We were one of the first to define how cofactors for eNOS influenced enzyme activity and function. Since that time we have expanded our studies to investigate fundamental mechanisms by which hsp90 modulates eNOS activity and function in cultured endothelial cells and in a variety of vascular tissues. We have investigated basic mechanisms by which hypercholesterolemia, sickle cell disease and systemic sclerosis impair vasodilatation and were the first to show that 4F, an apoA-I mimetic, increased vasodilatation in murine models of hypercholesterolemia, sickle cell disease and systemic sclerosis. More recently we have expanded our studies to investigate how HDL plays a critical role in decreasing pulmonary inflammation and collagen deposition in asthma and sickle cell disease.
As director of the Translation Vascular Biology Program I encourage all investigators in the program to develop strong interactions between basic and clinical scientists through weekly and monthly meetings and collaborative studies. Our mission is to understand the basic vascular biology and pathologies of various vascular diseases, to provide new tools and approaches for research and to develop novel therapeutic agents for fighting vascular disease in humans.
Selected Recent Publications
- 5. Du J, Wei N, Guan T, Xu H, An J, Pritchard Jr. KA, and Shi Y. Inhibition of CDKs by roscovitine suppressed LPS-induced •NO production through inhibiting NFkB activation and BH4 biosynthesis in macrophages. Am J Physiol Cell Physiol 2009; 297(3):C742-C749
- 6. Du J, Xu H, Wei N, Wakim B, Halligan B, Pritchard Jr. KA, Shi Y. Identification of proteins interacting with GTP cyclohydrolase I. Biochem Biophys Res Commun 2009;385(2):143-147
- 7. Larsen BT, Bubolz AH, Mendoza SA, Pritchard Jr., KA, Gutterman DD. Bradykinin-induced dilation of human coronary arterioles requires NADPH oxidase-derived reactive oxygen species. Arterioscler Thromb Vasc Biol 2009;29:739-745
- 8. Nandedkar S, Feroah T, Hutchins W, Weihrauch D, Konduri K, Wang J, Strunk R, DeBaun M, Hillery C, Pritchard Jr., KA. Histopathology of Experimentally-induced Asthma in a Murine Model of Sickle Cell Disease. Blood 2008;1126(6): 2529-2538
- 9. Frei AC, Guo Y, Jones DW, Pritchard Jr., KA, Fagan KA, Hogg N, Wandersee NJ. Vascular dysfunction in a murine model of severe hemolysis. Blood July 2008;112(2):398-405
- 10. Peterson DB, Sander T, Kaul S, Wakim BT, Halligan B, Twigger S, Pritchard Jr. KA, Oldham KT, Ou JS. Comparative proteomic analysis of PAI-1 and TNF-alpha-derived endothelial microparticles. Proteomics June 2008;8(12):2430-46