About

Gary V. Désir, MD, is the Paul B. Beeson Professor of Medicine at Yale School of Medicine and vice provost for Faculty Development at Yale University. He served as the chair of the Department of Internal Medicine from 2013 to 2025 and was chief of Internal Medicine at Yale New Haven Hospital. Dr. Désir is a physician-scientist whose work has been funded by the National Science Foundation, National Institute of Health, Department of Veterans Affairs, American Heart Association, and the Robert Wood Johnson foundation. His major scientific contributions include the discovery of a specific voltage-gated potassium channel that regulates body weight and insulin sensitivity, and the identification of a new growth factor named renalase. He elucidated the pathway through which renalase affects cellular signaling and discovered that the protein can function abnormally to facilitate the development of certain cancers. His laboratory is focused on developing drugs that can treat cancer by blocking the action of renalase in cancer cells. Dr. Désir is an inventor on several patents related to renalase and the development of renalase-based therapies, and he is the scientific founder of two biotechnology companies. Born in Port-Au-Prince, Haiti, he immigrated to the US after high school to attend New York University, graduating magna cum laude with a bachelor's degree in biology. He graduated from Yale University School of Medicine cum laude and Alpha Omega Alpha, and trained in internal medicine and nephrology at Yale New Haven Hospital. Dr. Désir has a strong interest in diversity and social justice, co-founding the minority organization for retention and expansion (MORE) at Yale School of Medicine. His research has significantly advanced understanding of renalase, a protein that regulates cell growth, survival, immune response, and has therapeutic relevance to diabetes, organ injury, and cancer. His work on renalase includes identifying its role as a secreted enzyme that protects against ischemic and toxic organ injury, and its overexpression in certain cancers where it promotes tumor cell survival. Additionally, Dr. Désir has contributed to the molecular physiology of voltage-gated potassium channels, identifying and characterizing various potassium channels in the kidney, including the molecular identity of channels involved in renal magnesium handling and cyclic GMP-activated potassium channels. His research continues to impact the fields of nephrology, cancer biology, and molecular physiology.

Research topics

• Immunology
• Medicine
• Internal medicine
• Biology
• Cancer research
• Physical therapy
• Genetics
• Endocrinology
• Microbiology
• Virology
• Biochemistry
• Pharmacology
• Cell biology

Selected publications

• Macrophages Derived from Renalase (RNLS) and Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 1 (Apobec1) Knockout Mice Fail to Rescue Cisplatin (CP)-Induced AKI

  Journal of the American Society of Nephrology · 2025-10-01

  articleSenior author
  PublisherDOI

• Renalase Activates Mitochondrial Leak Metabolism to Repair Mitochondrial Damage and Promote Cell Survival

  Journal of the American Society of Nephrology · 2025-10-01

  articleSenior author
  PublisherDOI

• Scalable automated segmentation quantifies mitochondrial proteins and morphology at the nanoscale

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-30 · 2 citations

  preprintOpen access

  Summary Ultrastructural changes of mitochondria are closely associated with metabolic dysfunction, leading to a variety of human disorders. These changes can be visualized by pan-Expansion Microscopy (pan-ExM), a 3D microscopy technique requiring only standard fluorescence microscopes, at a throughput exceeding that of the current gold standard, 3D electron microscopy, by orders of magnitude. However, a lack of tools that enable the characterization and quantification of the observed ultrastructural features in the acquired 3D datasets at a comparable throughput has hindered the widespread adoption of pan-ExM for quantitative imaging. Here, we present an automated deep-learning based segmentation approach that utilizes pan-ExM’s power to acquire multi-channel images and uses specific labeling as the annotation for the training of the segmentation network. This ‘molecular annotation’ reduces the required manual annotation effort for mitochondria substructures to just a few hours when setting up the experiment and thereby provides access to 3D suborganellar morphology of mitochondria at an unprecedented throughput. Our approach, which we term MAPS (Mitochondrial Automated Pan-ExM Segmentation), enables for the first time to quantify mitochondrial ultrastructural morphology at scale. We demonstrate this power by characterizing the 3D mitochondrial morphology at the organelle and sub-organelle level in tens of HeLa cells under different treatments and localizing mitochondrial proteins in the sub-organellar context. To demonstrate our technology in tissue, we compare the ultrastructural morphology of mitochondria in proximal tubules of kidneys of mice exhibiting acute kidney injury (AKI) with those of untreated mice, revealing striking differences in their cristae structure. MAPS can easily be adapted to different cell and tissue types, allowing the analysis of tens of samples per day, and therefore provides a versatile tool for a comprehensive understanding of mitochondrial ultrastructural changes in many disease contexts. Requiring only standard fluorescence microscopes and computer infrastructure, MAPS is readily adoptable by any lab. Highlights MAPS utilizes specific labeling to train a segmentation model for 3D super-resolution pan-ExM images Suborganellar mitochondrial features and their changes in disease models are quantified at high throughput 3D protein distributions are correlated to ultrastructural features in mitochondria Requiring only standard lab infrastructure, MAPS is readily adoptable

  PublisherOA PDFDOI

• Acute kidney injury markers in pediatric pancreatitis: Differentiating disease states and assessing severity

  Journal of Pediatric Gastroenterology and Nutrition · 2025-12-12

  articleOpen access

  OBJECTIVES: Acute kidney injury (AKI) is a complication commonly observed in adults with acute pancreatitis (AP) but remains poorly studied in pediatric patients. We investigated the utility of AKI biomarkers-kidney injury molecule-1 (KIM-1), lipocalin 2 (NGAL), cystatin-C (CYS-C), and renalase (RNLS) in acute and chronic pancreatitis (CP), and to assess AP severity, and evaluate kidney function. METHODS: Plasma and urine samples were collected from children with AP (n = 49), CP (n = 50), and healthy controls (HC; n = 20). AKI biomarkers levels were measured using enzyme-linked immunosorbent assays (ELISA). AP patients were categorized into two groups: mild AP (MAP) and moderate/severe AP (SAP). Kidney function was evaluated using plasma creatinine (pCre) and CYS-C-based enhanced glomerular filtration rate (eGFR) formulas. RESULTS: Plasma KIM-1 and pCYS-C were elevated in AP versus CP and HCs (p < 0.0001). Urinary NGAL (uNGAL) was elevated in AP subjects, with 14% of patients exceeding the value of 125 ng/mL. Plasma A-RNLS remained same between AP and HCs (p = 0.78) but was elevated in CP cohort (p < 0.0001). However, pF-RNLS levels declined in AP compared to HCs and CP (p < 0.0001). SAP subjects (20% of AP cohort) had elevated pKIM-1 and pCYS-C compared to MAP (p = 0.002, p = 0.003). eGFR declined in AP subjects with 84% of AP patients showing CYS-C eGFR <90 mL/min/1.73 m². Plasma CYS-C, pA-RNLS, and pF-RNLS predicted AP from CP with area under the receiving operating curve of 0.86 (95% CL). CONCLUSION: Elevated pKIM-1, pCYS-C, and uNGAL, along with declining pF-RNLS, are helpful in distinguishing pediatric AP from CP. Quantifying the Levels of pKIM-1 and pCYS-C within the first 48 h can help predict development of SAP.

  PublisherOA PDFDOI

• Association between plasma catecholamine concentration and mortality in hospitalized adults with COVID-19: a secondary analysis of a multicenter randomized trial

  Critical Care · 2025-05-08

  letterOpen access
  PublisherOA PDFDOI

• Renalase, HIV viremia, and all-cause mortality in people with and without HIV

  AIDS · 2025-07-10

  articleOpen accessSenior authorCorresponding

  Renalase is a pro-growth, immune-modulating protein. We examined plasma renalase concentrations in people with HIV (PWH) and people without HIV (PWoH) ( N = 2361). Renalase concentrations did not differ between PWH and PWoH. However, renalase concentrations were associated with higher viral loads. Among PWH, the subset with highest renalase concentrations demonstrated higher mortality independent of viral loads [adjusted hazard ratio 1.30; 95% confidence interval (CI) 1.03–1.64], identifying a previously unknown high-risk subset of PWH warranting further investigation.

  PublisherOA PDFDOI

• Renalase activates mitochondrial leak metabolism in response to cellular stress and to repair damage after injury

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-20 · 1 citations

  preprintOpen accessSenior author

  A variety of mechanisms enhance cell stress response and repair; however, the role of mitochondria in this activity is unclear. Here we show that exogenous renalase (RNLS), an intracellular flavin-dependent NADH oxidase, activates intramitochondrial RNLS activity to promote cell survival. RNLS interacts with the ATP synthase alpha and beta subunits (ATP5α and ATP5β) and opens the ATP synthase c-subunit leak channel to increase complex I and II activities and protein synthesis rate. RNLS causes a selective, sustained, time-dependent increase in cellular protein synthesis without affecting cell proliferation, whereas RNLS deletion or direct inhibition of the mitochondrial leak blocks RNLS-mediated protein synthesis. Functional analysis of newly and differentially synthesized proteins over 24 hours reveals rapid changes in one-carbon metabolism and ribosomal biogenesis pathways as early as one hour after RNLS exposure. Mitochondrial injury is more severe in the RNLS KO kidney after acute stress, related to decreased protein synthesis rate and increased mitophagy. RNLS KO mice exposed to the stress of chronic cardiac pressure overload fail to develop cardiac hypertrophy, the physiological response, and die of heart failure and cardiac rupture. These data highlight the critical role RNLS has in activating mitochondrial leak metabolism to induce selective protein synthesis and protect against acute and chronic stress. HIGHLIGHTS: Renalase interacts with the ATP synthase alpha and beta subunitsRenalase activates mitochondrial leak metabolismRenalase and leak metabolism increase complex I and II activitiesLeak metabolism increases protein synthesis rateRenalase protects against cell stress and organ injury.

  PublisherOA PDFDOI

• Visceral pain-related acute actions of cerulein on mouse and human sensory neurons

  Molecular Pain · 2025-06-16 · 4 citations

  articleOpen access

  Cerulein is an orthologue of cholecystokinin, which is often used to induce acute pancreatitis in pre-clinical studies. In these models, animals show signs of pain, and this is the most common complaint of patients with acute pancreatitis. However, little is known about how this pain is mediated, the role of cerulein murine pain responses, or its relevance to human pancreatitis pain. We injected 25 or 50 µg/kg cerulein intraperitoneally into male and female mice and assessed pain behaviors using the von Frey test of mechanical hypersensitivity. The excitability of mouse and human visceral dorsal root ganglia (DRG) neurons was assessed using whole-cell patch-clamp electrophysiology. Pharmacology was performed using commercial antagonists of cholecystokinin (CCK) A or B receptors. We show that pain behaviors developed similarly in male and female cerulein-injected mice and that visceral DRG from these mice exhibited increased excitability compared to controls. Direct application of cerulein to T8-L2 mouse and human DRG showed increased excitability compared to controls consistent with DRG from cerulein-injected mice. The actions of cerulein on visceral DRG neurons were attributed to CCK-A, but not CCK-B receptor. A similar response to cerulein was observed in human thoracic DRG neurons. These findings highlight the importance of the cholecystokinin system, particularly the CCK-A receptor, to visceral pain including pancreatitis through direct sensitization of visceral DRG neurons from mice or humans.

  PublisherDOI

• All-optical visualization of specific molecules in the ultrastructural context of brain tissue

  Nature Biotechnology · 2025-11-26 · 6 citations

  article
  PublisherDOI

• Renalase levels are decreased in maternal blood and placental tissues in pregnancies associated with preterm preeclampsia

  Scientific Reports · 2025-02-22

  articleOpen access

  Preeclampsia (PEC) is a complication of pregnancy associated with hypertension and the risk of eclampsia. The pathophysiology of PEC is unknown and identifying factors associated with PEC during pregnancy is crucial for placental, fetal, and maternal health. Renalase (RNLS) is an anti-inflammatory secretory flavoprotein associated with hypertension. Recent data demonstrated a correlation between maternal serum RNLS and PEC, and work from our group identified RNLS expression in the placenta. However, it remains unknown whether RNLS levels in placenta are altered by preeclampsia. Additionally, it is unclear if there is a differential effect of preterm and term PEC on RNLS. We demonstrate that serum RNLS was reduced in preterm cases of PEC. Similarly, placental RNLS was diminished in the chorion of preterm cases of PEC. However, a reduction of RNLS in the decidua was observed with all cases of PEC, while the levels of RNLS within the placental villi were similar in all cases. Overall, we demonstrate that RNLS correlates with PEC both systemically in maternal serum and locally within the placenta, with variable effects on the different layers of the placenta and more pronounced in preterm cases.

  PublisherOA PDFDOI

Frequent coauthors

• Heino Velázquez

  Centro de Implantología Cirugía Oral y Maxilofacial

  90 shared

• Robert L. Safirstein

  Connecticut Health Foundation

  87 shared

• Xiaojia Guo

  65 shared

• Fred S. Gorelick

  Yale University

  50 shared

• Peili Wang

  40 shared

• John Chang

  Yale University

  27 shared

• Guoyong Li

  West China Hospital of Sichuan University

  27 shared

• Charles Cha

  Velocity Clinical Research (United States)

  24 shared

Education

• M.D.

  Yale School of Medicine

Awards & honors

• 7 Regional Awards
• 2 National Awards