Overview
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 of integrated sciences: Ion and organic solute transport, mechanisms of cell growth and atrophy, and signal transduction. Areas of clinical research include hypertension and inheritable diseases. 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. The overall goal of our research program is 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 these conditions.
Areas of Research
Ion, Water and Urea Transport
Urine concentrating mechanisms are 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 4 isoforms of the urea transporter and are investigating their physiologic functions. The regulation of water via the aquaporin water transporters is being studied by Drs. Sands, Klein, Jennifer Gooch and Susan Wall. Dr. Wall has also identified Pendrin as a chloride channel and utilizes genetically modified mice to study its functions.
Mechanisms of Cell Growth and Atrophy
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. Drs. Harold Franch investigates the basis of abnormal cell growth in the kidney which includes decreased lysosomal proteolysis. Dr. Jennifer Gooch examines how changes in the activity of calcineurin, a Ca++ and calmodulin-dependent phosphatase contribute to glomerular hypertrophy. 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 system and caspase-3.
Signal Transduction
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 and Franch examine the role of phosphoinositol 3-kinase/Akt signaling in the regulation of the ubiquitin-proteasome and lysosomal proteolytic systems in kidney and muscle. Drs. Price and Gooch investigate how calcineurin impacts muscle protein metabolism and renal cell growth, respectively. Drs Sands and Klein are studying how protein kinase A regulates urea transport.
Hypertension and Inherited Causes of Kidney Disease
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 Arlene Chapman. In particular, Dr. Chapman 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). Genetic analysis of ADPKD includes detection of mutations in the PKD1 and PKD2 genes and polymorphisms in potential modifier genes. 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.