The Renal Division offers outstanding research opportunities in both basic and clinical/translational sciences research that is conducted in a collaborative environment.
Basic science research is weighted in three areas:
• Ion, water and urea transport
• Mechanisms of cell growth and atrophy
• Signal transduction
• Human neurophysiology
• Disease disparities and outcomes
• Vascular calcification
Projects are led by faculty who are experts in their respective fields, most of whom are supported by the NIH. The Division also has a NIH Training Grant to support M.D. and Ph.D. fellows who are interested in developing strong research skills for future academic careers and an R25 to support undergraduate students who are interested in a summer research experience. The overall goal of our research programs are to teach young investigators to apply modern research techniques to answer questions related to the causes and consequences of kidney disease and to develop new ways to treat these conditions.
Current Research Trials
The urine concentrating mechanism is important for normal homeostasis. Excretion and retention of water and a number of solutes are critical for normal renal physiology. Drs. Jeff Sands and Janet Klein have identified four isoforms of the urea transporter, and together with Dr. Mitsi Blount are investigating their physiologic functions. The regulation of water via the aquaporin water transporters is being studied by Drs. Sands, Klein, Blount and Susan Wall. Dr. Wall has also identified Pendrin as a chloride channel and utilizes genetically modified mice to study its functions. Drs. Hui Cai and Robert Hoover study the regulation of the sodium-potassium-chloride cotransporter in various models of hypertension.
In healthy cells, growth is regulated in part by the balance between protein synthesis and degradation. Diabetes, acidosis and other conditions cause excessive renal cell growth which can lead to kidney failure. Dr. Harold Franch investigates the basis of abnormal cell growth in the kidney which includes decreased lysosomal proteolysis. Other complications of diabetes and end-stage kidney disease include muscle atrophy, which results largely from excessive protein degradation. Drs. Russ Price, James Bailey, and Xiaonan Wang use biochemical and molecular biological techniques to study the mechanisms leading to increased proteolysis by the ubiquitin-proteasome, autophagy and caspase-3 systems.
The extracellular milieu regulates many intracellular functions by initiating cell signaling cascades. In the Renal Division, several faculty incorporate cell signaling into their research programs. Drs. Price, Wang and Franch examine the role of phosphoinositol 3-kinase/Akt/Foxo and other signaling pathways in the regulation of the genes involved in the ubiquitin-proteasome and lysosomal proteolytic systems in kidney and muscle. They also investigate how calcineurin impacts muscle protein metabolism.
Many of these investigators collaborate with Dr. Eaton, Chair of Physiology, and director of the Center for Cell and Molecular Signaling.
Clinical-epidemiologic studies that involve testing hypertensive African-American patients to identify whether they are in the “salt-sensitive” category, whether there are differences in the expression of candidate genes that affect the severity of hypertension in Caucasian compared to African-American patients, and building a registry of patients with polycystic kidney disease to determine if progression of renal failure can be linked to clinical characteristics or variations in genetic factors are areas of interest of Drs. Janice Lea and Frederic Rahbari. In particular, Dr. Rhabari utilizes iothalamate renal clearance and magnetic resonance determination of renal volume, cyst volume and renal blood flow in studies of autosomal dominant polycystic kidney disease (ADPKD). Studies also involve careful clinical characterization of patients with low renin hypertension, salt sensitivity and those at risk for primary hyperaldosteronism in conjunction with careful genotyping of their genetic background.
In other clinical research areas, Dr. Jeanie Park investigates derangements of neurovascular control in patients at high cardiovascular risk, particularly those with hypertension, chronic kidney disease (CKD), and stress disorders such as post-traumatic stress disorder (PTSD).
Dr. Charles O’Neill studies the underlying causes of increased vascular calcification in patients with CKD.
Dr. Plantinga investigates the sociodemographic and geographic determinants of quality of care among patients with chronic kidney disease (CKD), end-stage renal disease (ESRD), transplant and geriatric patients.