The major focus of Kishore Research Laboratory is the role of purinergic signaling in renal physiology, pathophysiology and experimental therapeutics. Purinergic signaling mediated by extracellular nucleotides, nucleosides and nucleobases is a relatively new area with a vast potential for developing a new class of drugs.

Besides uncovering many new phenomena, Kishore Lab identified P2Y receptors (P2Y2 and P2Y12, specifically) as potential targets from the development of innovative drugs to treat water balance disorders, such as acquired nephrogenic diabetes insipidus (NDI) and diet-induced obesity and insulin resistance. This work is being performed in collaboration with Drs. Donald E. Kohan, Raoul D. Nelson and Noel G. Carlson at the University of Utah, Dr. Carolyn M. Ecelbarger at the Georgetown University, Washington DC, and Prof. Christa Müller at the University of Bonn, Bonn, Germany. The work done in Kishore Lab in collaboration with Dr. Simon Robson at the Beth Israel Deaconess Medical Center & Harvard University, Boston, MA and Dr. Karen Dwyer at the Univ. of Victoria, Australia, uncovered the role of CD39 (NTPDase1) in the regulation of water and sodium handling by the kidney. Furthermore, in collaboration with Dr. Christof Westenfelder at the VA Medical Center and University of Utah, Kishore Lab developed a novel method for the induction of proliferation of erythropoietin-producing cells in the kidney, with potential therapeutic applications in anemia of chronic kidney disease. 

Clinical Relevance:

  • About 4% of the 20 million U.S. Veterans suffer from bipolar disorder, a sequel of PTSD (post-traumatic stress disorder). About 30% of bipolar Veterans receive chronic lithium therapy, which is often limited by the development of nephrogenic diabetes insipidus (NDI). Currently used modalities for the treatment of NDI are encountered with varying degrees of success as well as side effects. The studies conducted in Kishore Lab to gain in depth and integrated understanding of the role of renal purinergic signaling in lithium-induced NDI with a potential for the development of novel therapies, will benefit the Veterans Health Care.
  • Obesity and overweight, a global health problem, is not only an economic burden to the nations but is also the 5th risk factor for death (2.8 million deaths/year). In June 2013, the American Medical Association (AMA) officially recognized obesity as a disease. Despite these facts, currently there is a dearth of safe and efficacious medicines to prevent or treat diet-induced obesity, the most common form of obesity. The finding made by the Kishore Lab that P2Y2 receptor may play a significant role in diet-induced obesity and insulin resistance opened an avenue for further research.
kishore
Research Professor,
Nephrology & Hypertension