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Michelle L. Gumz, Ph.D. |
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Mechanism of the circadian clock in the kidney Many physiological processes exhibit a circadian pattern, including the sleep-wake cycle, heartbeat, hormone secretion, renal blood flow, and blood pressure. Disruption of these circadian patterns can result in disease states. For instance, while blood pressure decreases ("dips") at night in healthy individuals, "non-dipping" leads to an increased risk of cardiac death. The Gumz lab studies the molecular mechanism of the circadian clock in the kidney. The focus is on regulation of sodium transport in the kidney, which is critical to the control of blood pressure as well as to overall cardiovascular health. The mineralocorticoid hormone aldosterone regulates sodium balance and blood pressure. Dr. Gumz was the first to identify the circadian clock gene Per1 as an aldosterone target. Per1 regulates transcription of alpha ENaC, the aldosterone-regulated and rate-limiting subunit of the epithelial sodium channel. In vitro experiments are routinely performed using several cell culture models of the renal collecting duct. Electrophysiology will be used to measure sodium transport in these cell lines. In vivo work includes the use of radio-telemetry to evaluate blood pressure in Per1 knockout mice. Using microarray analysis, real time PCR, Western blotting, and analysis of DNA/protein interactions, the Gumz lab continues to identify novel Per1 targets and to determine how these targets contribute to the regulation of sodium transport in the kidney. |
Status: Accepting New Students This Year Contact Information: office: Communicore CG-92B lab: Communicore CG-92 phone: 352-273-6887 email: Michelle.Gumz@medicine.ufl.edu |
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Figure Legend. Mechanisms of Sodium, Potassium, Chloride and Water Transport in a Renal Cortical Collecting Duct Principal Cell. Proteins denoted by the "clock" symbol are the products of genes that are expressed in an apparent circadian pattern. Na+, sodium; K+, potassium; Cl-, chloride; H2O, water; ENaC, epithelial sodium channel; GILZ, glucocorticoid-induced leucine zipper protein; Usp2, ubiquitin-specific protease 2; SGK1, serum and glucocorticoid-regulated kinase; ET-1, endothelin-1; Nedd4-2, neural precursor cell expressed, developmentally down-regulated gene 4-like; V1aR, vasopressin 1a receptor; V2R, vasopressin 2 receptor. |
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