Associate Professor of Medicine
Division of Endocrinology, Department of Medicine
Health Research Center, H4145
(414) 955-8452 | firstname.lastname@example.org
I study the biology of kidney transporter proteins SLC5A1 (SGLT1), SLC5A2 (SGLT2), and SLC5A4 (SGLT3), and investigate their roles in the pathogenesis of diabetes and heavy metal cadmium toxicity. SGLT1 and SGLT2 are sodium-dependent glucose transporters that mediate glucose reabsorption in the kidney. The amino acid sequence of SGLT3 is highly homologous to that of SGLT1 and SGLT2; however, SGLT3 is not a glucose transporter but instead mediates the transport of sodium in the presence of glucose. So far, little is known about the role of SGLT3 in the kidney.
We have generated different tools and methods to study changes in expression, regulation, and function of SGLTs in human kidney tissues and in kidneys of mouse and rat models. My laboratory’s technical areas of expertise include kidney primary cell and cell line cultures, promoter activity and gene expression analyses, in vitro and in vivo measurements of transcription factor activity, and protein expression and localization analyses. Also, my laboratory has established unique fluorescence spectroscopic and microscopic techniques to measure sodium-dependent and –independent transports of glucose and to measure intracellular concentration of sodium in cultured kidney cells and in cell lines transiently over-expressing SGLT.
Diabetic nephropathy is the leading cause of end-stage kidney disease. Hypertension is associated with diabetes and elevated blood pressure has been recognized as a risk factor for the development of diabetic nephropathy. Hypertension in diabetes is believed to be secondary to increased sodium reabsorption in the kidney. My laboratory investigates the role of SGLT3 in diabetes-mediated increased renal sodium reabsorption by examining SGLT3 expression and function in vitro and in vivo. Our studies have shown for the first time the expression of SGLT3 in human kidney homogenate samples in vivo and in human proximal tubule HK-2 cell line in vitro. Mouse has two genes that encode SGLT3a and SGLT3b, and we have shown mRNA expressions of both in mouse kidney homogenates in vivo and in primary cultures of mouse kidney cells in vitro. Our functional studies have shown that the transient over-expression of human SGLT3 in COS-7 cells or its pharmacological activation in HK-2 cells increases intracellular level of sodium concentration. We are investigating the role of this novel kidney sodium transporter in the pathogenesis of diabetes.
Cadmium Nephrotoxicity Research
Cadmium is a heavy metal and an environmental pollutant. Chronic exposure to cadmium results in the accumulation of this toxic metal in the kidney and causes Fanconi-like syndrome, a generalized proximal tubule dysfunction, which is manifested by the loss of nutrients including glucose in the urine. My laboratory investigates the mechanism of cadmium-induced glucosuria. Our studies have shown that exposure of primary cultures of mouse kidney cells to cadmium results in down-regulation of glucose uptake, and in parallel, decreases mRNA expressions of Sglt1 and Sglt2 genes. We investigate the inhibitory effects of cadmium on the activity of zinc finger transcription factor Sp1 as mechanism of transcriptional down-regulations of SGLT1 and SGLT2 expressions.
Division of Endocrinology, Metabolism and Clinical Nutrition
Department of Medicine
9200 W. Wisconsin Ave.
Milwaukee, WI 53226
(414) 955-6724 or (414) 955-6723
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Froedtert Hospital's Endocrinology and Diabetes Services
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
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