Kidney, diabetes, dopamine, colorectal cancer, 11betaHSD2, COX-2, LOX
My research focuses on three main areas:
1) Hormonal regulation of renal physiological and pathophysiologic functions. Specifically, we have investigated the regulation of renal cortical and medullary cyclooxygenase-2 (COX-2) expression by different hormones including elements of the renin-angiotensin system, dopaminergic system, adrenal corticosteroids, vasopressin, and others. We have also investigated the regulation of renal COX-2 by type II 11ß hydroxysteroid dehydrogenase (11ßHSD2) elevation of intracellular glucocorticoids. We are now intensively investigating the interaction between the intrarenal dopaminergic system and the intrarenal renin-angiotensin system using genetically manipulated mice with either elevated or reduced intrarenal dopaminergic activity.
2) 11ßHSD2 and colorectal tumorigenesis. COX-2 expression increases in colorectal tumors. Inhibition of COX-2 activity suppresses colorectal tumorigenesis. Both COX-2 and 11ßHSD2 expression are elevated in colorectal adenomas. Glucocorticoids are potent endogenous 11ßHSD2 inhibitors. Inhibition of 11ßHSD2 activity elevates levels of intracellular glucocorticoids in tumor cells, leading to inhibition of both COX-2 and tumorigenesis.
3) Immunohistochemistry in the kidney, application of image analysis and tissue microarray (TMA) in kidney research.