Thomas D. DuBose, Jr., M.D.
Professor and Chair of Internal Medicine
Additional Titles: Professor of Physiology and Pharmacology
Telephone: (336) 716-2715
Fax: (336) 716-2273
Email: tdubose@wfubmc.edu
Education: 1966 B.S. University of Alabama
1966-1970 M.D. University of Alabama at Birmingham School of Medicine
Board Certification: April 16, 1973 American Board of Internal Medicine
June 27, 1978 American Board of Internal Medicine, Nephrology
Research Interests:
Regulation of renal transporters; Potassium balance; Molecular description of transporters responsible for urinary acidification; Expression and molecular regulation of non-gastric H+,K+-ATPases in kidney and distal colon, aldosterone deficiency and excess; Renal tubular acidosis; Clinical acid-base and electrolyte disorders.
Current Research:
Current Projects
The goal of studies in my laboratory is to elucidate factors involved in the molecular regulation of tubule transporters involved in urinary acidification and potassium conservation. Many of these transporters have been implicated in monogenic diseases associated with renal tubular acidosis, or abnormalities in potassium homeostasis and blood pressure regulation. Our studies highlight correlation between regulation of transport protein abundance and function at the cellular level. Current studies are designed to investigate the contribution of Na+,K+-ATPases and H+,K+-ATPases in the kidney and distal colon. Our laboratory was the first to show that while both gastric and colonic a-subunits of the H+,K+-ATPase are expressed in kidney, the colonic a H+,K+-ATPase is selectively and site-specifically up-regulated in the outer medullary collecting duct by potassium deprivation in an animal model of chronic hypokalemia (2, 4). We have also shown that, while, unlike the gastric a H+,K+-ATPase there is no unique β-subunit for the colonic a H+,K+-ATPase (HKa2), β1-Na+,K+-ATPase (NKβ1) functions as the physiologic β-subunit in kidney and distal colon (1). Both subunits are translocated to the apical membrane in distal colon, and in transiently transfected HEK 293 cells (5). Moreover, the carboxy terminus of the colonic a H+,K+-ATPase is critical for β subunit protection of the a-subunit and translocation of the heterodimer to the apical membrane (5, 6). Recently, we have demonstrated that HKa2 - NKβ1 translocation and function is critically dependent on interaction with the tetraspanin protein CD63 (3). CD63 appears to function as a negative regulatory interacting protein that is responsible for the internalization of HKa2 - Naβ1 and thereby, regulation of function (manuscript under review). The techniques employed in these studies include cell culture, Northern and Western blot analysis, transient transfection, site-directed mutagenesis, immunofluorescence, imaging, and siRNA.
Recent Publications:
1. Codina, J., Li, J., Hong,Y., and DuBose, T.D.: The g-Na+,K+-ATPase subunit assembles selectively with a1/b1-Na+,K+-ATPAse but not with colonic H+,K+-ATPase. Kidney Intern. 61:967-974, 2002.
2. King, T.E., Jr., Dickinson, T.A., DuBose, T.D., Jr., Flack, J.M., Hellmann, D.B., Pamies, R.J., Todd, R.F., III, Torres, E.A., and Wesson, D.E.: The Case for Diversity in Academic Internal Medicine. The American Journal of Medicine, 116:284-289, 2004.
3. Li, J., Codina, J., Petroske, E., Werle, M.J., and DuBose, T.D., Jr.: The carboxy terminus of the colonic H+,K+-ATPase a-subunit is required for stable b-subunit assembly and function. Kidney International, 65:1-10, 2004.
4. Codina, J., Li, J., and DuBose, T.D., Jr.: A carboxy terminus motif of HKa2 is necessary for assembly and function. Kidney International, 66:1068-1075, 2004.
5. Codina, J., Li, J., and DuBose, T.D., Jr.: CD63 interacts with the carboxy terminus of the colonic H+-K+-ATPase to increase plasma membrane localization and 86Rb+ uptake. Am. J. Physiol. Cell Physiol. 288:C1279-C1286, 2005.
Publications:
For a listing of additional publications, refer to PubMed, a service provided by the National Library of Medicine