Education & Training
- M.D.,Case Western Reserve University- 1998
- B.S., University of Michigan-1993
Research Interest Summary
Research Categories
Research Interests
We are a team of molecular biologists, cell physiologists, and kidney-oriented physicians who aim to understand how salt and water homeostasis is regulated from cell to organism. Most of our work is centered on the WNK-SPAK/OSR1 pathway, a network of serine-threonine kinases that forms biomolecular condensates: membraneless cytoplasmic subdomains that assemble via phase transitions. WNK signaling condensates emerged in unicellular organisms to control cell fluid volume and size through the sensing of intracellular molecular crowding. Ultimately, however, these regulatory mechanisms were co-opted to control clinically relevant processes such as blood pressure and potassium homeostasis via the formation of specialized kidney-specific condensates termed WNK bodies. A fundamental principle that drives our work centers around unraveling how ion transport is coordinated in cells, and across tissues and organ systems. We strive to understand these processes to translate them to physiology and clinical practice.
Representative Publications
Boyd-Shiwarski CR, Shiwarski DJ, Griffiths SE, Beacham RT, Norrell L, Morrison DE, Wang J, Mann J, Tennant W, Anderson EN, Franks J, Calderon M, Connolly KA, Cheema MU, Weaver CJ, Nkashama LJ, Weckerly CC, Querry KE, Pandey UB, Donnelly CJ, Sun D, Rodan AR, Subramanya AR. WNK kinases sense molecular crowding and rescue cell volume via phase separation. Cell 2022 Nov 23; 185(24):4488-4506. Epub Oct 25. PMID: 36318922.
Boyd-Shiwarski CR, Weaver CJ, Beacham RT, Shiwarski DJ, Connolly KA, Nkashama LJ, Mutchler SM, Griffiths SE, Knoell SA, Sebastiani RS, Ray EC, Marciszyn AL, Subramanya AR. Effects of extreme potassium stress on blood pressure and renal tubular sodium transport. Am J Physiol – Renal Physiol. 2020 Jun 1;318(6):F1341-F1356. Epub 2020 Apr 13. PMID: 32281415.
Boyd-Shiwarski CR, Shiwarski DJ, Roy A, Nkashama LJ, Namboodiri HN, Xie J, McClain KL, Marciszyn A, Kleyman TR, Tan RJ, Stolz DB, Puthenveedu MA, Huang CL, Subramanya AR. Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent. Mol Biol Cell 2018 Feb 15;29(4):499-509. Epub 2017 Dec 13. PMID: 29237822.
Al-Qusairi L, Basquin D, Roy A, Rajamram RD, Maillard M, Subramanya AR, Staub O. Renal tubular ubiquitin protein ligase NEDD4-2 is required for renal adaptation during long-term potassium depletion. J Am Soc Nephrol. 2017 Aug;28(8):2431-2442. Epub 2017 Mar 13. PMID: 2829184.
Roy A, Al-Qusairi L, Donnelly BF, Ronzaud C, Marciszyn AL, Gong F, Chang YPC, Butterworth MB, Pastor-Soler NM, Hallows KR, Staub O, Subramanya AR. Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action. J Clin Invest 2015 Sep;125(9):3433-48. Epub 2015 Aug 4. PMID: 26241057
Donnelly BF, Needham PG, Snyder AC, Roy A, Khadem S, Brodsky JL, Subramanya AR. Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter ER-associated degradation and biogenesis. J Biol Chem. 2013 May 3;288(18):13124-35. Epub 2013 Mar 12.