| || Education |
B.A., Hampton University, Hampton, VA (Biology)
Ph.D., University of Texas Medical Branch, Galveston, TX (Pharmacology)
Post-Doc Training: Baylor College of Medicine, Houston, TX (Physiology)
Armed Forces Radiobiology Research Institute, Bethesda, MD (Physiology)
Dr. Colden directs NIH-funded research characterizing the role of ion channels in macrophage and endothelial cell function during adhesion events and implications in the pathogenesis of cardiovascular diseases and diabetes. We have demonstrated that there is a time-dependent increase in the expression of an inwardly rectifying K+ (Kir) current with a concomitant decrease in a delayed rectifier K+ (Kdr) current in human leukemiaTHP-1 monocytes adherent to activated human endothelial cells or immobilized vascular cell adhesion molecule-1 (VCAM-1). This interaction between very late activation antigen-4 (VLA-4) integrins on the surface of monocytes with VCAM-1 produces a hyperpolarization via the increased Kir to enhance the driving force for Ca2+ entry and thus, Ca2+-dependent cytokine production. Our immediate directions are to confirm at the RNA and protein levels the K+ channel species that underlies the VLA-induced whole-cell ionic currents.
We also culture primary bone marrow-derived macrophages to investigate the role of Kir channels in the activation and differentiation of monocytes into macrophages as a first step in atherosclerotic lesion formation in apoE-deficient mice as well as kidney end-organ damage in salt-induced hypertension in Dahl-salt sensitive rats. Additionally, we have been studying macrophage function (oxidative stress, cytokine production) and its modulation by Kir and Kdr channels in human peripheral blood derived-macrophages from lean or obese African-American women with Metabolic Syndrome. It is our hope that our work may lead to a better understanding of signaling events fundamental to monocyte activation, differentiation, and cardiovascular diseases and diabetes which disproportionately affect minorities.
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