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Gary Désir, MD

Vice Provost for Faculty Development and Diversity; Chair, Department of Internal Medicine; and Paul B. Beeson Professor of Medicine; Affiliated Faculty, Yale Institute for Global Health

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Gary Désir, MD

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  • Internal Medicine

    PO Box 208056, 330 Cedar Street

    New Haven, CT 06520-8056

    United States

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Research Summary

Discovery and naming of renalase (RNLS): a novel protein that regulates cell growth and survival, modulates the immune system and has therapeutic relevance to type 1 diabetes, acute cellular and organ injury, and to cancer

Renalase is a novel renal hormone that was discovered in our laboratory. It is synthesized by the proximal tubule and secreted in plasma where it metabolizes catecholamines and signals via a receptor-mediated pathway to enhance cell survival. Renalase deficiency aggravates renal and cardiac ischemic injury, and administration of recombinant renalase protects against ischemic and toxic acute kidney injury (AKI) and myocardial necrosis. Single nucleotide polymorphisms of the renalase gene are associated with essential hypertension, stroke and type 1 diabetes. We are currently investigating the molecular mechanisms mediating the direct cellular protective effect of renalase, its utility as a therapeutic agent for ischemic and toxic AKI, and as a potential biomarker for AKI.

Identification and validation of therapeutic targets for the treatment of obesity and diabetes

Voltage-gated potassium (Kv) channels regulate cell membrane potential and control a variety of cellular processes including insulin secretion. We found that the voltage-gated channel Kv1.3 and its signaling cascade represented a novel, pathway that regulates body weight and peripheral glucose metabolism. Inhibitors of Kv1.3 could prove useful in the management of obesity and diabetes.

Specialized Terms: Hypertension; Diabetes, Acute kidney injury; Catecholamines metabolism; immune regulation

Extensive Research Description

CONTRIBUTION TO SCIENCE

1- Discovery and naming of renalase (RNLS): a novel protein that regulates cell growth and survival, modulates the immune system and has therapeutic relevance to type 1 diabetes, acute cellular and organ injury, and to cancer. (2001-present)

The development of chronic kidney disease is associated with such a remarkable propensity of developing cardiovascular complications that the yearly risk of death is the same for 25-year-old person with end-stage kidney as it is for one who is 80 years old but has normal kidney function. In 2001 I decided to focus my research efforts on investigating the mechanisms underlying this observation and hypothesized that the kidney was producing a yet to be discovered protein that was secreted in plasma and that modulated cardiovascular function. We employed molecular and computer modeling methods to identify an unknown protein I named renalase (RNLS). It is a flavin adenine dinucleotide–dependent (FAD-dependent) amine oxidase that is secreted into the blood by the kidney, that appeared to metabolize circulating catecholamines and NADH, and regulate blood pressure.

Intracellularly, RNLS functions as an enzyme that participates in the metabolism of NADH and NADPH, The secreted form of RNLS is a survival factor that protects against ischemic and toxic organ injury (heart, kidney, liver and pancreas) independently of its enzymatic function. And it does so by activating a receptor-mediated, pro-survival signaling cascade (MAPK, AKT and STAT3). We have identified the key region of the RNLS molecule that mediates its cyto-protective action and have used this information to show the plasma membrane calcium ATPase isoform, PMCA4b functions as a receptor for extracellular RNLS.

Recent insights into RNLS’ pathophysiology relate to its overexpression in select human cancers, where it signals through specific pathways to promote the survival of cancer cells. RNLS modulates the immune system to inhibit recognition of tumor antigens through a pathway that does not overlap with that of the known checkpoint proteins. Secreted RNLS may turn out to be the original checkpoint protein given that it is ~3 billion years old and highly conserved throughout evolution.

Our most recent work indicates that RNLS could serve as a prognostic marker, and inhibitors of the RNLS pathway will be first-in-class therapeutics for the treatment of melanoma, pancreatic, breast and lung cancer. I am an inventor on several issued patents related to discovery and use of RNLS and the scientific inventor of 2 biotech companies.

2- Molecular physiology of voltage-gated potassium channels 1992-2006

a- Molecular identity of potassium (K) channels in kidney: voltage-gated K channels (1992)

A variety of potassium (K) channels had been detected in the mammalian kidney using electrophysiological methods. Although the physiological roles of some of these channels were unclear at the time, voltage-gated K (Kv) channels were postulated to participate in at least two important processes, K recycling and K secretion. The structure of renal K channels were not known at the time, and there was great interest in identifying genes encoding these channels.

The first member of the Shaker gene family (encodes Kv channels) had recently been identified using a mutant fly called Shaker. Although Shaker gene expression was believed to be restricted to excitable cells, and Shaker-like currents had not been detected by electrophysiological methods, we hypothesized that renal tubular cells involved in ion transport should experience changes in membrane voltage that are substantial enough to activate Kv channels. Therefore, we used PCR and degenerate oligonucleotides based on conserved Shaker sequences to probe for the expression of Shaker-like genes in rabbit kidney and the pig renal epithelial cell line LLC-PK1. These studies led to the identification of several Shaker related genes in mammalian. This was the first demonstration that Shaker-like genes were expressed in any epithelial cell. We subsequently showed that Kv1.1 was highly expressed in the distal tubule.

Subsequent to our work, genetics studies in families with hereditary forms of renal magnesium wasting have established that Kv1.1 is a key palyer in renal magnesium handling. Work carried out by the laboratory of Rene Bindels has provided convincing evidence that Kv1.1 maintains an inside negative membrane potential that drives magnesium entry via the transient receptor potential channel TRPM6 into renal distal tubular cell.

b- Identification of a new class of cyclic GMP-activated K channel (1995)

The molecular structures of Kv, calcium-activated (Kca), and ATP-regulated (Katp) potassium channels had been elucidated, and there was considerable interest in determining the structure of nucleotide-activated (Knuc) K channels since they were thought to play important roles in the maintenance of arterial tone and in the process of insulin secretion. The molecular structure of a class of ion channels that were gated by cyclic nucleotides but do not discriminate between sodium and potassium (nonselective cation channels) was known. They all contain a cyclic nucleotide binding region located at the C terminus. Sequence analysis indicates that these channels were distantly related to voltage-gated Shaker K channels.

Based on these data and on the fact that cyclic nucleotides were known to regulate renal K-channel activity we hypothesized that Knuc might share structural motifs with both Shaker K channels and cyclic nucleotide-gated cation channels. We used degenerate primers for the conserved Shaker regions and the cGMP binding domains to identify a novel member of the K channel gene family (Kcn1 or KCNA10) expressed in kidney and encoding a K-selective channel that is specifically activated by cGMP. This protein defines a class of K channels that has structural features common to voltage-gated Shaker-like K channels and to cyclic nucleotide-gated nonselective cation channels.

c- Cloning of KCNK1, the first two-pore K channel identified in man (1997)

It was clear that potassium channels exhibited great functional and structural diversity, and four major structural classes encoding a-subunits with two, four, six, or eight trans-membrane segments (TM) were known at the time. The 2-TM and 6-TM structural classes had been extensively studied in mammals and shown to consist of families, which were themselves divided into subfamilies made up of many members. In contrast to the 2-TM and 6-TM classes, which have been well characterized in many species including mammals, virtually nothing was known about the 4-TM and 8-TM classes of K channels. Data from the C. elegans genome sequencing project suggested that the 4-TM class of K channels contains at least 23 different genes.

These channels display the unusual structural feature of having two putative pore regions in contrast to all previously cloned K channels (2-TM and 6-TM), which only have one pore. The first member (TOK1) of the 8-TM class, had recently been identified in yeast, had two pore domains and encoded an outward-rectifying K channel. A 4-TM K channel cloned from Drosophila also had two pores and mediated K currents with outward rectification dependent on external K concentration.

We used computer modeling and database mining to identify mammalian sequences encoding putative double pore channels. This work resulted in the cloning and characterization of the first two-pore K channel (KCNK1) identified in man. We also showed that expression of KCNK1 in rabbit kidney was limited to the distal nephron. Fifteen two-pore channels have subsequently been identified in mammals, and they play key roles in cell and organ physiology, and are regulated by several mechanisms, including oxygen tension, pH, mechanical stretch and G-proteins.

d- The voltage-gated Kv1.3 channel regulates body weight and insulin sensitivity (2004)

Kv1.3 is a Shaker-related, voltage-gated potassium (Kv) channel expressed in many tissues. Examination of Kv1.3-deficient mice (Kv1.3 KO) generated by gene targeting, revealed a previously unrecognized role for Kv1.3 in body weight regulation. Kv1.3KO mice weigh less than control littermates and are protected from diet-induced obesity. Indeed, when maintained on a high-fat diet for up to 7 months, they gain less weight than control littermates. Most likely channel inhibition increased basal metabolic rate.

Interestingly, although Kv1.3 KO mice exposed to a high-fat diet become obese, they are euglycemic and have normal blood insulin levels. This observation, along with the fact that Kv1.3 activity is regulated by insulin in the olfactory bulb, prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity. We showed that Kv1.3 is an important component of the pathways that regulate glucose homeostasis. Inhibition of channel activity, either by gene deletion or by channel blockers, significantly increases peripheral insulin sensitivity by recruiting GLUT4 to the plasma membrane by down-regulating IL-6 and TNF secretion and JNK activity. The channel and its signaling pathway represent potential targets for the development of drugs useful in the management of diabetes. I am an inventor on an issued a patent covering compositions and methods relating inhibition of Kv1.3 to improve glucose metabolism, and control weight control and food intake (Patent number US 6,861,405 B2, USA 2005).

Coauthors

Research Interests

Catecholamines; Diabetes Mellitus; Hypertension; Internal Medicine; Obesity; Acute Kidney Injury

Selected Publications

  • Identification of Two Forms of Human Plasma Renalase, and Their Association With All-Cause Mortality.Chang J, Guo X, Rao V, Gromisch ES, Chung S, Kluger HM, Cha C, Gorelick F, Testani J, Safirstein R, Crowley S, Peixoto AJ, Desir GV. Identification of Two Forms of Human Plasma Renalase, and Their Association With All-Cause Mortality. Kidney International Reports 2020, 5: 362-368. PMID: 32154458, PMCID: PMC7056858, DOI: 10.1016/j.ekir.2019.12.002.
  • Decreased plasma levels of the survival factor renalase are associated with worse outcomes in COVID-19.Wang M, Guo X, Chun HJ, Lee AI, Cha C, Gorelick F, Desir GV. Decreased plasma levels of the survival factor renalase are associated with worse outcomes in COVID-19. MedRxiv : The Preprint Server For Health Sciences 2020 PMID: 32577678, PMCID: PMC7302283, DOI: 10.1101/2020.06.02.20120865.
  • Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia.Safdar B, Guo X, Johnson C, D'Onofrio G, Dziura J, Sinusas AJ, Testani J, Rao V, Desir G. Elevated renalase levels in patients with acute coronary microvascular dysfunction - A possible biomarker for ischemia. International Journal Of Cardiology 2019, 279: 155-161. PMID: 30630613, PMCID: PMC6482834, DOI: 10.1016/j.ijcard.2018.12.061.
  • Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease.Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.
  • New chief of cardiovascular medicine at Yale School of Medicine.Desir GV, Churchwell KB. New chief of cardiovascular medicine at Yale School of Medicine. European Heart Journal 2018, 39: 1665. PMID: 29762704, DOI: 10.1093/eurheartj/ehy197.
  • Extracellular renalase protects cells and organs by outside-in signalling.Wang Y, Safirstein R, Velazquez H, Guo XJ, Hollander L, Chang J, Chen TM, Mu JJ, Desir GV. Extracellular renalase protects cells and organs by outside-in signalling. Journal Of Cellular And Molecular Medicine 2017, 21: 1260-1265. PMID: 28238213, PMCID: PMC5487909, DOI: 10.1111/jcmm.13062.
  • The serum protein renalase reduces injury in experimental pancreatitis.Kolodecik TR, Reed AM, Date K, Shugrue C, Patel V, Chung SL, Desir GV, Gorelick FS. The serum protein renalase reduces injury in experimental pancreatitis. The Journal Of Biological Chemistry 2017, 292: 21047-21059. PMID: 29042438, PMCID: PMC5743078, DOI: 10.1074/jbc.M117.789776.
  • A Remote Role for Renalase.Giordano FJ, Wang Y, Desir GV. A Remote Role for Renalase. EBioMedicine 2016, 9: 27-28. PMID: 27374133, PMCID: PMC4972559, DOI: 10.1016/j.ebiom.2016.06.034.
  • Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD.Torres R, Velazquez H, Chang JJ, Levene MJ, Moeckel G, Desir GV, Safirstein R. Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD. Journal Of The American Society Of Nephrology : JASN 2016, 27: 1102-12. PMID: 26303068, PMCID: PMC4814184, DOI: 10.1681/ASN.2015010079.
  • Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer.Guo X, Hollander L, MacPherson D, Wang L, Velazquez H, Chang J, Safirstein R, Cha C, Gorelick F, Desir GV. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Scientific Reports 2016, 6: 22996. PMID: 26972355, PMCID: PMC4789641, DOI: 10.1038/srep22996.
  • Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism.Hollander L, Guo X, Velazquez H, Chang J, Safirstein R, Kluger HM, Cha C, Desir G. Renalase Expression by Melanoma and Tumor-Associated Macrophages Promotes Tumor Growth through a STAT3-Mediated Mechanism. Cancer Research 2016, 76: 3884-94. PMID: 27197188, PMCID: PMC5031238, DOI: 10.1158/0008-5472.CAN-15-1524.
  • Renalase regulates peripheral and central dopaminergic activities.Quelhas-Santos J, Serrão MP, Soares-Silva I, Fernandes-Cerqueira C, Simões-Silva L, Pinho MJ, Remião F, Sampaio-Maia B, Desir GV, Pestana M. Renalase regulates peripheral and central dopaminergic activities. American Journal Of Physiology. Renal Physiology 2015, 308: F84-91. PMID: 25411385, PMCID: PMC4338928, DOI: 10.1152/ajprenal.00274.2014.
  • Identification of a receptor for extracellular renalase.Wang L, Velazquez H, Chang J, Safirstein R, Desir GV. Identification of a receptor for extracellular renalase. PloS One 2015, 10: e0122932. PMID: 25906147, PMCID: PMC4407985, DOI: 10.1371/journal.pone.0122932.
  • Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.Qi C, Wang L, Zhang M, Shao X, Chang X, Fan Z, Cao Q, Mou S, Wang Q, Yan Y, Desir G, Ni Z. Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis. PloS One 2015, 10: e0139627. PMID: 26431044, PMCID: PMC4592194, DOI: 10.1371/journal.pone.0139627.
  • Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke.Guo X, Wang L, Velazquez H, Safirstein R, Desir GV. Renalase: its role as a cytokine, and an update on its association with type 1 diabetes and ischemic stroke. Current Opinion In Nephrology And Hypertension 2014, 23: 513-8. PMID: 24992568, PMCID: PMC4383282, DOI: 10.1097/MNH.0000000000000044.
  • Renalase in hypertension and kidney disease.Desir GV, Peixoto AJ. Renalase in hypertension and kidney disease. Nephrology, Dialysis, Transplantation : Official Publication Of The European Dialysis And Transplant Association - European Renal Association 2014, 29: 22-8. PMID: 24137013, DOI: 10.1093/ndt/gft083.
  • Renalase prevents AKI independent of amine oxidase activity.Wang L, Velazquez H, Moeckel G, Chang J, Ham A, Lee HT, Safirstein R, Desir GV. Renalase prevents AKI independent of amine oxidase activity. Journal Of The American Society Of Nephrology : JASN 2014, 25: 1226-35. PMID: 24511138, PMCID: PMC4033373, DOI: 10.1681/ASN.2013060665.
  • Renalase regulates renal dopamine and phosphate metabolism.Sizova D, Velazquez H, Sampaio-Maia B, Quelhas-Santos J, Pestana M, Desir GV. Renalase regulates renal dopamine and phosphate metabolism. American Journal Of Physiology. Renal Physiology 2013, 305: F839-44. PMID: 23863468, PMCID: PMC3761288, DOI: 10.1152/ajprenal.00616.2012.
  • Does kidney disease cause hypertension?Peixoto AJ, Orias M, Desir GV. Does kidney disease cause hypertension? Current Hypertension Reports 2013, 15: 89-94. PMID: 23344662, DOI: 10.1007/s11906-013-0327-6.
  • Renalase protects against ischemic AKI.Lee HT, Kim JY, Kim M, Wang P, Tang L, Baroni S, D'Agati VD, Desir GV. Renalase protects against ischemic AKI. Journal Of The American Society Of Nephrology : JASN 2013, 24: 445-55. PMID: 23393318, PMCID: PMC3582209, DOI: 10.1681/ASN.2012090943.
  • Renalase lowers ambulatory blood pressure by metabolizing circulating adrenaline.Desir GV, Tang L, Wang P, Li G, Sampaio-Maia B, Quelhas-Santos J, Pestana M, Velazquez H. Renalase lowers ambulatory blood pressure by metabolizing circulating adrenaline. Journal Of The American Heart Association 2012, 1: e002634. PMID: 23130169, PMCID: PMC3487338, DOI: 10.1161/JAHA.112.002634.
  • Novel insights into the physiology of renalase and its role in hypertension and heart disease.Desir G. Novel insights into the physiology of renalase and its role in hypertension and heart disease. Pediatric Nephrology (Berlin, Germany) 2012, 27: 719-25. PMID: 21424526, DOI: 10.1007/s00467-011-1828-7.
  • Human renalase: a review of its biology, function, and implications for hypertension.Desir GV, Wang L, Peixoto AJ. Human renalase: a review of its biology, function, and implications for hypertension. Journal Of The American Society Of Hypertension : JASH 2012, 6: 417-26. PMID: 23107895, DOI: 10.1016/j.jash.2012.09.002.
  • Renalase deficiency aggravates ischemic myocardial damage.Wu Y, Xu J, Velazquez H, Wang P, Li G, Liu D, Sampaio-Maia B, Quelhas-Santos J, Russell K, Russell R, Flavell RA, Pestana M, Giordano F, Desir GV. Renalase deficiency aggravates ischemic myocardial damage. Kidney International 2011, 79: 853-60. PMID: 21178975, DOI: 10.1038/ki.2010.488.
  • Increased renal dopamine and acute renal adaptation to a high-phosphate diet.Weinman EJ, Biswas R, Steplock D, Wang P, Lau YS, Desir GV, Shenolikar S. Increased renal dopamine and acute renal adaptation to a high-phosphate diet. American Journal Of Physiology. Renal Physiology 2011, 300: F1123-9. PMID: 21325500, PMCID: PMC3094044, DOI: 10.1152/ajprenal.00744.2010.
  • Role of renalase in the regulation of blood pressure and the renal dopamine system.Desir GV. Role of renalase in the regulation of blood pressure and the renal dopamine system. Current Opinion In Nephrology And Hypertension 2011, 20: 31-6. PMID: 21099685, DOI: 10.1097/MNH.0b013e3283412721.
  • The evidence-based use of thiazide diuretics in hypertension and nephrolithiasis.Reilly RF, Peixoto AJ, Desir GV. The evidence-based use of thiazide diuretics in hypertension and nephrolithiasis. Clinical Journal Of The American Society Of Nephrology : CJASN 2010, 5: 1893-903. PMID: 20798254, DOI: 10.2215/CJN.04670510.
  • A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.Farzaneh-Far R, Desir GV, Na B, Schiller NB, Whooley MA. A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study. PloS One 2010, 5: e13496. PMID: 20975995, PMCID: PMC2958117, DOI: 10.1371/journal.pone.0013496.
  • Renalase, a novel soluble FAD-dependent protein, is synthesized in the brain and peripheral nerves.Hennebry SC, Eikelis N, Socratous F, Desir G, Lambert G, Schlaich M. Renalase, a novel soluble FAD-dependent protein, is synthesized in the brain and peripheral nerves. Molecular Psychiatry 2010, 15: 234-6. PMID: 20168325, DOI: 10.1038/mp.2009.74.
  • A case of extreme hemodynamic lability and hypocalcemia.Knauf F, Desir GV, Perazella MA. A case of extreme hemodynamic lability and hypocalcemia. The American Journal Of The Medical Sciences 2009, 338: 241-4. PMID: 19590425, DOI: 10.1097/MAJ.0b013e3181a66af1.
  • Regulation of blood pressure and cardiovascular function by renalase.Desir GV. Regulation of blood pressure and cardiovascular function by renalase. Kidney International 2009, 76: 366-70. PMID: 19471322, DOI: 10.1038/ki.2009.169.
  • Catecholamines regulate the activity, secretion, and synthesis of renalase.Li G, Xu J, Wang P, Velazquez H, Li Y, Wu Y, Desir GV. Catecholamines regulate the activity, secretion, and synthesis of renalase. Circulation 2008, 117: 1277-82. PMID: 18299506, DOI: 10.1161/CIRCULATIONAHA.107.732032.
  • Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease.Desir GV. Renalase deficiency in chronic kidney disease, and its contribution to hypertension and cardiovascular disease. Current Opinion In Nephrology And Hypertension 2008, 17: 181-5. PMID: 18277152, DOI: 10.1097/MNH.0b013e3282f521ba.
  • Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII.Li Y, Wang P, Xu J, Gorelick F, Yamazaki H, Andrews N, Desir GV. Regulation of insulin secretion and GLUT4 trafficking by the calcium sensor synaptotagmin VII. Biochemical And Biophysical Research Communications 2007, 362: 658-64. PMID: 17720139, PMCID: PMC2194288, DOI: 10.1016/j.bbrc.2007.08.023.
  • Renalase is a novel renal hormone that regulates cardiovascular function.Desir GV. Renalase is a novel renal hormone that regulates cardiovascular function. Journal Of The American Society Of Hypertension : JASH 2007, 1: 99-103. PMID: 20409839, DOI: 10.1016/j.jash.2006.12.001.
  • Renalase, a new renal hormone: its role in health and disease.Xu J, Desir GV. Renalase, a new renal hormone: its role in health and disease. Current Opinion In Nephrology And Hypertension 2007, 16: 373-8. PMID: 17565281, DOI: 10.1097/MNH.0b013e3281bd8877.
  • Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma membrane via a Ca2+-dependent mechanism.Li Y, Wang P, Xu J, Desir GV. Voltage-gated potassium channel Kv1.3 regulates GLUT4 trafficking to the plasma membrane via a Ca2+-dependent mechanism. American Journal Of Physiology. Cell Physiology 2006, 290: C345-51. PMID: 16403947, DOI: 10.1152/ajpcell.00091.2005.
  • Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure.Xu J, Li G, Wang P, Velazquez H, Yao X, Li Y, Wu Y, Peixoto A, Crowley S, Desir GV. Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure. The Journal Of Clinical Investigation 2005, 115: 1275-80. PMID: 15841207, PMCID: PMC1074681, DOI: 10.1172/JCI24066.
  • Kv1.3 potassium channel blockade as an approach to insulin resistance.Desir GV. Kv1.3 potassium channel blockade as an approach to insulin resistance. Expert Opinion On Therapeutic Targets 2005, 9: 571-9. PMID: 15948674, DOI: 10.1517/14728222.9.3.571.
  • Molecular diversity and regulation of renal potassium channels.Hebert SC, Desir G, Giebisch G, Wang W. Molecular diversity and regulation of renal potassium channels. Physiological Reviews 2005, 85: 319-71. PMID: 15618483, PMCID: PMC2838721, DOI: 10.1152/physrev.00051.2003.
  • The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity.Xu J, Wang P, Li Y, Li G, Kaczmarek LK, Wu Y, Koni PA, Flavell RA, Desir GV. The voltage-gated potassium channel Kv1.3 regulates peripheral insulin sensitivity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 3112-7. PMID: 14981264, PMCID: PMC365752, DOI: 10.1073/pnas.0308450100.
  • The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight.Xu J, Koni PA, Wang P, Li G, Kaczmarek L, Wu Y, Li Y, Flavell RA, Desir GV. The voltage-gated potassium channel Kv1.3 regulates energy homeostasis and body weight. Human Molecular Genetics 2003, 12: 551-9. PMID: 12588802, DOI: 10.1093/hmg/ddg049.
  • International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels.Gutman GA, Chandy KG, Adelman JP, Aiyar J, Bayliss DA, Clapham DE, Covarriubias M, Desir GV, Furuichi K, Ganetzky B, Garcia ML, Grissmer S, Jan LY, Karschin A, Kim D, Kuperschmidt S, Kurachi Y, Lazdunski M, Lesage F, Lester HA, McKinnon D, Nichols CG, O'Kelly I, Robbins J, Robertson GA, Rudy B, Sanguinetti M, Seino S, Stuehmer W, Tamkun MM, Vandenberg CA, Wei A, Wulff H, Wymore RS. International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels. Pharmacological Reviews 2003, 55: 583-6. PMID: 14657415, DOI: 10.1124/pr.55.4.9.
  • On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial sodium transport.Segal AS, Hayslett JP, Desir GV. On the natriuretic effect of verapamil: inhibition of ENaC and transepithelial sodium transport. American Journal Of Physiology. Renal Physiology 2002, 283: F765-70. PMID: 12217868, DOI: 10.1152/ajprenal.00253.2001.
  • The distal convoluted tubule of rabbit kidney does not express a functional sodium channel.Velázquez H, Silva T, Andújar E, Desir GV, Ellison DH, Greger R. The distal convoluted tubule of rabbit kidney does not express a functional sodium channel. American Journal Of Physiology. Renal Physiology 2001, 280: F530-9. PMID: 11181416, DOI: 10.1152/ajprenal.2001.280.3.F530.
  • Haemophilus parainfluenzae liver abscess in a recipient of a renal transplant who had polycystic disease.Desir G, Helman D, Herlich M, Turka L, Bia MJ. Haemophilus parainfluenzae liver abscess in a recipient of a renal transplant who had polycystic disease. JAMA 1986, 255: 1878. PMID: 3512876.
  • Effect of hyperketonemia on renal ammonia excretion in man.Desir G, Bratusch-Marrain P, DeFronzo RA. Effect of hyperketonemia on renal ammonia excretion in man. Metabolism: Clinical And Experimental 1986, 35: 736-43. PMID: 3736414.
  • Detection of acute allograft rejection by indium-111 labeled platelet scintigraphy in renal transplant patients.Desir G, Bia MJ, Lange RC, Smith EO, Kashgarian M, Flye W, Schiff M, Ezekowitz MD. Detection of acute allograft rejection by indium-111 labeled platelet scintigraphy in renal transplant patients. Transplantation Proceedings 1987, 19: 1677-80. PMID: 3547876.
  • A Ca-activated K channel from rabbit renal brush-border membrane vesicles in planar lipid bilayers.Zweifach A, Desir GV, Aronson PS, Giebisch GH. A Ca-activated K channel from rabbit renal brush-border membrane vesicles in planar lipid bilayers. The American Journal Of Physiology 1991, 261: F187-96. PMID: 1713419, DOI: 10.1152/ajprenal.1991.261.1.F187.
  • High affinity binding of amiloride analogs at an internal site in renal microvillus membrane vesicles.Desir GV, Cragoe EJ, Aronson PS. High affinity binding of amiloride analogs at an internal site in renal microvillus membrane vesicles. The Journal Of Biological Chemistry 1991, 266: 2267-71. PMID: 1846621.
  • Reconstitution and partial purification of an amiloride-sensitive, cation channel from rabbit kidney.Desir GV. Reconstitution and partial purification of an amiloride-sensitive, cation channel from rabbit kidney. Biochimica Et Biophysica Acta 1991, 1067: 38-42. PMID: 1868102.
  • Solubilization and partial purification of the thiazide diuretic receptor from rabbit renal cortex.Ellison DH, Morrisey J, Desir GV. Solubilization and partial purification of the thiazide diuretic receptor from rabbit renal cortex. Biochimica Et Biophysica Acta 1991, 1069: 241-9. PMID: 1932064.
  • Inhibition of Ca-activated K+ channels from renal microvillus membrane vesicles by amiloride analogs.Zweifach A, Desir GV, Aronson PS, Giebisch G. Inhibition of Ca-activated K+ channels from renal microvillus membrane vesicles by amiloride analogs. The Journal Of Membrane Biology 1992, 128: 115-22. PMID: 1501239, DOI: 10.1007/bf00231884.
  • Isolation of putative voltage-gated epithelial K-channel isoforms from rabbit kidney and LLC-PK1 cells.Desir GV, Hamlin HA, Puente E, Reilly RF, Hildebrandt F, Igarashi P. Isolation of putative voltage-gated epithelial K-channel isoforms from rabbit kidney and LLC-PK1 cells. The American Journal Of Physiology 1992, 262: F151-7. PMID: 1733291, DOI: 10.1152/ajprenal.1992.262.1.F151.
  • Molecular physiology of renal potassium channels.Desir G. Molecular physiology of renal potassium channels. Seminars In Nephrology 1992, 12: 531-40. PMID: 1475548.
  • Identification of a novel K-channel gene (KC22) that is highly expressed in distal tubule of rabbit kidney.Desir GV, Velázquez H. Identification of a novel K-channel gene (KC22) that is highly expressed in distal tubule of rabbit kidney. The American Journal Of Physiology 1993, 264: F128-33. PMID: 7679255, DOI: 10.1152/ajprenal.1993.264.1.F128.
  • Immunocytochemical characterization of the high-affinity thiazide diuretic receptor in rabbit renal cortex.Ellison DH, Biemesderfer D, Morrisey J, Lauring J, Desir GV. Immunocytochemical characterization of the high-affinity thiazide diuretic receptor in rabbit renal cortex. The American Journal Of Physiology 1993, 264: F141-8. PMID: 8430824, DOI: 10.1152/ajprenal.1993.264.1.F141.
  • Primary structure and functional expression of a cGMP-gated potassium channel.Yao X, Segal AS, Welling P, Zhang X, McNicholas CM, Engel D, Boulpaep EL, Desir GV. Primary structure and functional expression of a cGMP-gated potassium channel. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 11711-5. PMID: 8524834, PMCID: PMC40472.
  • The structure, regulation and pathophysiology of potassium channels.Desir GV. The structure, regulation and pathophysiology of potassium channels. Current Opinion In Nephrology And Hypertension 1995, 4: 402-5. PMID: 8564442.
  • Molecular characterization of voltage and cyclic nucleotide-gated potassium channels in kidney.Desir GV. Molecular characterization of voltage and cyclic nucleotide-gated potassium channels in kidney. Kidney International 1995, 48: 1031-5. PMID: 8569064.
  • Molecular cloning of a glibenclamide-sensitive, voltage-gated potassium channel expressed in rabbit kidney.Yao X, Chang AY, Boulpaep EL, Segal AS, Desir GV. Molecular cloning of a glibenclamide-sensitive, voltage-gated potassium channel expressed in rabbit kidney. The Journal Of Clinical Investigation 1996, 97: 2525-33. PMID: 8647945, PMCID: PMC507338, DOI: 10.1172/JCI118700.
  • Genomic structure and regulation of Kcn1, a cGMP-gated potassium channel.Yao X, Liu Y, Tung F, Desir GV. Genomic structure and regulation of Kcn1, a cGMP-gated potassium channel. The American Journal Of Physiology 1996, 271: F37-41. PMID: 8760241, DOI: 10.1152/ajprenal.1996.271.1.F37.
  • Rabbit distal convoluted tubule coexpresses NaCl cotransporter and 11 beta-hydroxysteroid dehydrogenase II mRNA.Velázquez H, Náray-Fejes-Tóth A, Silva T, Andújar E, Reilly RF, Desir GV, Ellison DH. Rabbit distal convoluted tubule coexpresses NaCl cotransporter and 11 beta-hydroxysteroid dehydrogenase II mRNA. Kidney International 1998, 54: 464-72. PMID: 9690213, DOI: 10.1046/j.1523-1755.1998.00036.x.
  • Genomic localization of the human gene for KCNA10, a cGMP-activated K channel.Orias M, Bray-Ward P, Curran ME, Keating MT, Desir GV. Genomic localization of the human gene for KCNA10, a cGMP-activated K channel. Genomics 1997, 42: 33-7. PMID: 9177773, DOI: 10.1006/geno.1997.4712.
  • Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments.Orias M, Velázquez H, Tung F, Lee G, Desir GV. Cloning and localization of a double-pore K channel, KCNK1: exclusive expression in distal nephron segments. The American Journal Of Physiology 1997, 273: F663-6. PMID: 9362344.
  • Characterization of a regulatory region in the N-terminus of rabbit kv1.3.Yao X, Huang Y, Kwan HY, Chan P, Segal AS, Desir G. Characterization of a regulatory region in the N-terminus of rabbit kv1.3. Biochemical And Biophysical Research Communications 1998, 249: 492-8. PMID: 9712724.
  • Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman's syndrome.Kunchaparty S, Palcso M, Berkman J, Velázquez H, Desir GV, Bernstein P, Reilly RF, Ellison DH. Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman's syndrome. The American Journal Of Physiology 1999, 277: F643-9. PMID: 10516289, DOI: 10.1152/ajprenal.1999.277.4.F643.
  • The T0 domain of rabbit KV1.3 regulates steady state channel protein level.Segal AS, Yao X, Desir GV. The T0 domain of rabbit KV1.3 regulates steady state channel protein level. Biochemical And Biophysical Research Communications 1999, 254: 54-64. PMID: 9920732, DOI: 10.1006/bbrc.1998.9801.
  • Expression of KCNA10, a voltage-gated K channel, in glomerular endothelium and at the apical membrane of the renal proximal tubule.Yao X, Tian S, Chan HY, Biemesderfer D, Desir GV. Expression of KCNA10, a voltage-gated K channel, in glomerular endothelium and at the apical membrane of the renal proximal tubule. Journal Of The American Society Of Nephrology : JASN 2002, 13: 2831-9. PMID: 12444201, DOI: 10.1097/01.asn.0000036866.37886.c5.
  • Close association of the N terminus of Kv1.3 with the pore region.Yao X, Liu W, Tian S, Rafi H, Segal AS, Desir GV. Close association of the N terminus of Kv1.3 with the pore region. The Journal Of Biological Chemistry 2000, 275: 10859-63. PMID: 10753881.
  • KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels.Lang R, Lee G, Liu W, Tian S, Rafi H, Orias M, Segal AS, Desir GV. KCNA10: a novel ion channel functionally related to both voltage-gated potassium and CNG cation channels. American Journal Of Physiology. Renal Physiology 2000, 278: F1013-21. PMID: 10836990, DOI: 10.1152/ajprenal.2000.278.6.F1013.
  • Regulation of the voltage-gated K+ channel KCNA10 by KCNA4B, a novel beta-subunit.Tian S, Liu W, Wu Y, Rafi H, Segal AS, Desir GV. Regulation of the voltage-gated K+ channel KCNA10 by KCNA4B, a novel beta-subunit. American Journal Of Physiology. Renal Physiology 2002, 283: F142-9. PMID: 12060596, DOI: 10.1152/ajprenal.00258.2001.
  • Challenges in interpreting cytokine data in COVID-19 affect patient care and management.Wang SY, Takahashi T, Pine AB, Damsky WE, Simonov M, Zhang Y, Kieras E, Price CC, King BA, Siegel MD, Desir GV, Lee AI, Iwasaki A, Chun HJ. Challenges in interpreting cytokine data in COVID-19 affect patient care and management. PLoS Biology 2021, 19: e3001373. PMID: 34358229, PMCID: PMC8372945, DOI: 10.1371/journal.pbio.3001373.
  • Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease.Pointer TC, Gorelick FS, Desir GV. Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease. Cells 2021, 10 PMID: 34440775, PMCID: PMC8391834, DOI: 10.3390/cells10082006.
  • Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma.Gao Y, Wang M, Guo X, Hu J, Chen TM, Finn SMB, Lacy J, Kunstman JW, Cha CH, Bellin MD, Robert ME, Desir GV, Gorelick FS. Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma. PloS One 2021, 16: e0250539. PMID: 34587190, PMCID: PMC8480607, DOI: 10.1371/journal.pone.0250539.
  • Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation.Guo X, Xu L, Velazquez H, Chen TM, Williams RM, Heller DA, Burtness B, Safirstein R, Desir GV. Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation. Journal Of The American Society Of Nephrology : JASN 2022, 33: 342-356. PMID: 34921111, PMCID: PMC8819981, DOI: 10.1681/ASN.2021040439.
  • Inhibition of renalase drives tumour rejection by promoting T cell activation.Guo X, Jessel S, Qu R, Kluger Y, Chen TM, Hollander L, Safirstein R, Nelson B, Cha C, Bosenberg M, Jilaveanu LB, Rimm D, Rothlin CV, Kluger HM, Desir GV. Inhibition of renalase drives tumour rejection by promoting T cell activation. European Journal Of Cancer (Oxford, England : 1990) 2022, 165: 81-96. PMID: 35219026, PMCID: PMC8940682, DOI: 10.1016/j.ejca.2022.01.002.
  • A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste.Chupp G, Spichler-Moffarah A, Søgaard OS, Esserman D, Dziura J, Danzig L, Chaurasia R, Patra KP, Salovey A, Nunez A, May J, Astorino L, Patel A, Halene S, Wang J, Hui P, Patel P, Lu J, Li F, Gan G, Parziale S, Katsovich L, Desir GV, Vinetz JM. A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste. MedRxiv : The Preprint Server For Health Sciences 2022 PMID: 35132421, PMCID: PMC8820673, DOI: 10.1101/2022.01.28.22270035.
  • Association of renalase with clinical outcomes in hospitalized patients with COVID-19.Safdar B, Wang M, Guo X, Cha C, Chun HJ, Deng Y, Dziura J, El-Khoury JM, Gorelick F, Ko AI, Lee AI, Safirstein R, Simonov M, Zhou B, Desir GV. Association of renalase with clinical outcomes in hospitalized patients with COVID-19. PloS One 2022, 17: e0264178. PMID: 35259186, PMCID: PMC8903289, DOI: 10.1371/journal.pone.0264178.
  • Associations of Renalase With Blood Pressure and Hypertension in Chinese Adults.Wang Y, Chen C, Hu GL, Chu C, Zhang XY, Du MF, Zou T, Zhou Q, Liao YY, Ma Q, Wang KK, Sun Y, Wang D, Yan Y, Li Y, Jia H, Niu ZJ, Zhang X, Wang L, Man ZY, Gao WH, Li CH, Zhang J, Gao K, Li HX, Chang J, Desir GV, Lu WH, Mu JJ. Associations of Renalase With Blood Pressure and Hypertension in Chinese Adults. Frontiers In Cardiovascular Medicine 2022, 9: 800427. PMID: 35282385, PMCID: PMC8907541, DOI: 10.3389/fcvm.2022.800427.
  • Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation.Wang M, Silva T, Toothaker JM, McCourt BT, Shugrue C, Desir G, Gorelick F, Konnikova L. Renalase and its receptor, PMCA4b, are expressed in the placenta throughout the human gestation. Scientific Reports 2022, 12: 4953. PMID: 35322081, PMCID: PMC8943056, DOI: 10.1038/s41598-022-08817-6.
  • Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study.Wang Y, Zhao P, Chu C, Du MF, Zhang XY, Zou T, Hu GL, Zhou HW, Jia H, Liao YY, Chen C, Ma Q, Wang D, Yan Y, Sun Y, Wang KK, Niu ZJ, Zhang X, Man ZY, Wu YX, Wang L, Li HX, Zhang J, Li CH, Gao WH, Gao K, Lu WH, Desir GV, Delles C, Chen FY, Mu JJ. Associations of Long-Term Visit-to-Visit Blood Pressure Variability With Subclinical Kidney Damage and Albuminuria in Adulthood: a 30-Year Prospective Cohort Study. Hypertension 2022, 79: 1247-1256. PMID: 35360932, PMCID: PMC9093226, DOI: 10.1161/HYPERTENSIONAHA.121.18658.
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