Peter S. Aronson MD

C. N. H. Long Professor of Medicine (Nephrology) and Professor of Cellular and Molecular Physiology

Research Interests

Urinary electrolyte excretion; Cell membrane ion exchangers; Proximal tubule

Current Projects

  • Regulation of Na+-H+ exchanger NHE3 in the proximal tubule, a process important for controlling the salt, fluid, and acid-base balance of the body.
  • Roles of SLC26 anion exchangers in directly and indirectly governing urinary oxalate excretion, a urinary constituent that is very important for kidney stone formation.

Research Summary

The general goal of our research is to understand how the kidney regulates the salt (NaCl) and acid-base balance of the body. To eliminate waste products from the body, the kidney filters gigantic quantities of the plasma (over 160 quarts per day) resulting in the flow of huge quantities of water, NaCl and the base bicarbonate through the renal tubules. The first portion of each renal tubule is called the proximal tubule, and the proximal tubules are collectively responsible for reabsorbing the vast majority of the filtered NaCl, bicarbonate and water, and secreting acid in the form of ammonium ions.

Our lab has specifically focused on identifying the proteins involved in mediating the transport of bicarbonate, NaCl and ammonium in the proximal tubule. We found that “knockout” mice lacking one of these transport proteins have a high incidence of calcium oxalate urinary stones, the same type that is most common in human patients with kidney stones. We showed that the cause of the calcium oxalate kidney stones is a very high concentration of oxalate in the urine. We found that this kidney transport protein also plays a very crucial role in the intestine, where it secretes oxalate and thereby limits how much of ingested oxalate is absorbed and then excreted in the urine. Based on this discovery, our laboratory has been devoting increasing effort to understanding the role of transporters in governing oxalate homeostasis and excretion.

Extensive Research Description

Our general goal is to characterize the mechanisms regulating sodium, acid-base, and anion excretion by the kidney. Our work is primarily focused on membrane transport proteins mediating ion exchange, namely NHE isoforms mediating Na+-H+ exchange, and SLC26 isoforms mediating anion exchange. One approach involves the generation of isoform-specific polyclonal and monoclonal antibodies to identify the cellular and subcellular sites of expression of ion exchangers in the kidney and other tissues, and to study their biosynthesis and assembly into multimeric complexes. A complementary approach uses mice with targeted gene disruption to elucidate the physiological roles of ion exchangers and associated proteins under in vivo conditions. For example, work with mice lacking anion exchanger Slc26a6, which can function as an oxalate transporter, revealed a phenotype of calcium oxalate kidney stones. This finding in turn has motivated studies of the roles and regulation of anion transporters affecting oxalate homeostasis under normal conditions and in diseases associated with hyperoxaluria.

Selected Publications

  • Knauf, F., Asplin, J.R., Granja, I., Schmidt, I.M., Moeckel, G., David, R., Flavell, R.A., and Aronson, P.S. NALP3-mediated inflammation is the principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 84:895-901, 2013
  • Hayashi, H., Tamura, A., Krishnan, D., Tsukita, S., Suzuki, Y., Kocinsky, H.S., Aronson, P.S., Orlowski, J., Grinstein, S., and Alexander, R.T. Ezrin is required for the functional regulation of the epithelial sodium proton exchanger, NHE3. PLoS One 8:e55623, 2013
  • Ko, N., Knauf, F., Jiang, Z., Markovich, D., and Aronson, P.S. Sat1 is dispensable for active oxalate secretion in mouse duodenum. Am. J. Physiol. 303:C52-C57, 2012.
  • Hassan, H.A., Cheng, M., and Aronson, P.S. Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells. Am. J. Physiol. 302:C46-C58, 2012.
  • Knauf, F., Ko, N., Jiang, Z., Robertson, W.G., Van Itallie, C.M., Anderson, J.M., and Aronson, P.S. Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J. Am. Soc. Nephrol. 22:2247-2255, 2011.
  • Knauf, F., and Aronson, P.S. ESRD as a window into America’s cost crisis in health care. J. Am. Soc. Nephrol. 20: 2093–2097, 2009.
  • Kocinsky HS, Dynia DW, Wang T, Aronson PS. NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity. Am J Physiol, 293:F212-8, 2007.
  • Jiang Z, Asplin JR, Evan AP, Rajendran VM, Velazquez H, Nottoli TP, Binder HJ, Aronson PS. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nat Genet, 38:474-8, 2006.

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