Gary Désir, MD
Vice Provost for Faculty Development and Diversity; Chair, Department of Internal Medicine; and Paul B. Beeson Professor of MedicineCards
Administrative Support
Publications Overview
- 117 Publications
- 3,989 Citations
- 74 Yale Co-Authors
Honors
- 7 Regional Awards
- 2 National Awards
Administrative Support
Publications Overview
- 117 Publications
- 3,989 Citations
- 74 Yale Co-Authors
Honors
- 7 Regional Awards
- 2 National Awards
Administrative Support
Publications Overview
- 117 Publications
- 3,989 Citations
- 74 Yale Co-Authors
Honors
- 7 Regional Awards
- 2 National Awards
About
The Yale Department of Internal Medicine provides outstanding, compassionate, and equitable care to our patients. We are dedicated to the development of new knowledge, aspire to train and inspire the next generation of leaders in medicine, and are committed to cultivating an inclusive, collaborative, and professional culture.
Titles
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
Biography
Gary V. Désir, MD, is the Paul B. Beeson Professor of Medicine and chair of the Department of Internal Medicine at Yale School of Medicine and vice provost for Faculty Development and Diversity at Yale University. He also serves as chief of Internal Medicine at Yale New Haven Hospital.
He 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 contributions to science 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, which he named renalase. He elucidated the pathway through which renalase affects cellular signaling and discovered that the protein can function abnormally and facilitate the development of certain cancers. His laboratory is currently focused on developing drugs that can treat cancer by blocking the action of renalase in cancer cells. Dr. Désir is a named inventor on several patents related to the discovery and therapeutic use of renalase, and the development of drugs that modulate renalase signaling in cancer. He is the scientific founder of 2 biotechnology companies focused on developing renalase-based therapies.
Dr. Désir, the first person of African descent to be appointed as chair of a department at YSM, has a strong interest in issues of diversity and social justice. He is the co-founder of the minority organization for retention and expansion (MORE), a faculty group at YSM focused on increasing faculty diversity through mentoring programs and developing resilient social networks. In collaboration with Gordon Geballe, Associate Dean for Alumni and External Affairs at school of Forestry and Environmental Studies, he has worked with L’Hospital Albert Schweitzer in the Artibonite valley in Haiti on integrated projects designed to improve the standard of living in the valley.
He was born in Port-Au-Prince, Haiti. After high school, he immigrated to the US to attend New York University, from which he graduated magna cum laude, with a bachelor’s degree in biology. He was elected to the Phi Beta Kappa Society, and also received New York University’s Founders Day award. Following graduation from Yale University School of Medicine (Cum Laude, Alpha Omega Alpha honor society), he trained in internal medicine and nephrology at Yale New Haven Hospital.
Dr. Désir is married to Dr. Deborah Dyett Désir who practices rheumatology at Yale. They have four children, Carl, Matthew, Christopher and Alexandra, a granddaughter Elodie and a grandson Amari.
Appointments
Internal Medicine
ChairDualInternal Medicine
ProfessorPrimary
Other Departments & Organizations
Education & Training
- Post-Doc Associate
- Yale School of Medicine (1988)
- Fellow
- Yale School of Medicine (1984)
- Resident
- Yale School of Medicine (1983)
- MD
- Yale University, Cum Laude (1980)
Research
Overview
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).
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Fred Sanford Gorelick, MD
Xiaojia (Sasha) Guo, PhD
Robert Safirstein, MD
Tian-Min Chen
Gilbert Moeckel, MD, PhD, FASN
Aldo Peixoto, MD
Hypertension
Catecholamines
Acute Kidney Injury
Diabetes Mellitus
Obesity
Publications
2024
Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival
Zaman S, Gorelick F, Chrobrutskiy A, Chobrutskiy B, Desir G, Blanck G. Chemical complementarity of tumor resident, T-cell receptor CDR3s and renalase-1 correlates with increased melanoma survival. Oncotarget 2024, 15: 550-561. PMID: 39102218, PMCID: PMC11299663, DOI: 10.18632/oncotarget.28633.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsT cell receptorOverall survivalT cellsAssociated with improved overall survivalT-cell receptor CDR3sPromote T cell activationImproved overall survivalSurvival of melanomaPancreatic cancer patientsT cell activationT cell receptor recognitionTumor-residentTumor rejectionMelanoma patientsMelanoma growthMelanoma survivalImmune signature genesSurvival associationsCancer patientsMelanomaSignature genesAmino acid sequenceSurvivalPatientsExpression levelsRenalase Peptides Reduce Pancreatitis Severity in Mice
Kolodecik T, Guo X, Shugrue C, Guo X, Desir G, Wen L, Gorelick F. Renalase Peptides Reduce Pancreatitis Severity in Mice. AJP Gastrointestinal And Liver Physiology 2024 PMID: 39010833, DOI: 10.1152/ajpgi.00143.2024.Peer-Reviewed Original ResearchConceptsAcute pancreatitisRecombinant renalaseProsurvival propertiesSeverity of acute pancreatitisModel of acute pancreatitisAcute inflammatory injuryClinically relevant modelAnti-inflammatoryHistological tissue injuryPost-ERCPCerulein modelCerulein-inducedInitial dosePancreatitis severityPreclinical modelsImmunohistochemical markersQuantify inflammationInflammatory changesMale micePancreatitisMacrophage populationsTissue injuryCerulein pancreatitisTherapeutic effectRenalaseCOMBINED EFFECTS OF CHILD AND ADULT ELEVATED BLOOD PRESSURE ON ADULT SUBCLINICAL KIDNEY DAMAGE AND ALBUMINURIA: A 36-YEAR PROSPECTIVE COHORT STUDY
Wang Y, Jia H, Du M, Sun Y, Wang D, Hu G, Man Z, Chu C, Desir G, Safirstein R, Zheng X, Mu J. COMBINED EFFECTS OF CHILD AND ADULT ELEVATED BLOOD PRESSURE ON ADULT SUBCLINICAL KIDNEY DAMAGE AND ALBUMINURIA: A 36-YEAR PROSPECTIVE COHORT STUDY. Journal Of Hypertension 2024, 42: e204. DOI: 10.1097/01.hjh.0001021508.55729.ea.Peer-Reviewed Original ResearchConceptsPersistently elevated BPUrinary albumin-to-creatinine ratioAlbumin-to-creatinine ratioElevated BPSubclinical kidney damageIncreased riskBlood pressureAdult BPCreatinine ratioElevated urinary albumin-to-creatinine ratioEffects of childrenParticipants aged 6Self-reported useKidney damageRisk of chronic kidney diseaseAssociated with increased riskAssociated with increased risk of chronic kidney diseaseChildhood elevated BPNational Health Commission of the People's Republic of ChinaRisk of albuminuriaElevated blood pressureChronic kidney diseaseChildhood to adulthoodCohort studyLongitudinal cohortRenalase Identified by Machine Learning Methods as A Novel Independent Predictor of Mortality in Hospitalized Patients with COVID-19
Safdar B, Sobiesk M, Bertsimas D, Nowroozpoor A, Deng Y, D’Onofrio G, Dziura J, El-Khoury J, Guo X, Simonov M, Taylor R, Wang M, Desir G. Renalase Identified by Machine Learning Methods as A Novel Independent Predictor of Mortality in Hospitalized Patients with COVID-19. Journal Of Biotechnology And Biomedicine 2024, 07 DOI: 10.26502/jbb.2642-91280139.Peer-Reviewed Original ResearchConcepts
2023
Clinical predictive value of renalase in post-ERCP pancreatitis
Muniraj T, Desir G, Gorelick F, Guo X, Ciarleglio M, Deng Y, Jamidar P, Farrell J, Aslanian H, Laine L. Clinical predictive value of renalase in post-ERCP pancreatitis. Gastrointestinal Endoscopy 2023, 99: 822-825.e1. PMID: 38103747, DOI: 10.1016/j.gie.2023.12.020.Peer-Reviewed Original ResearchAltmetricConceptsPost-ERCP pancreatitisRenalase levelsPlasma renalase levelsProspective cohort studyPotential clinical roleAcute experimental pancreatitisLongitudinal regression modelsPEP patientsPlasma renalaseCohort studyTertiary hospitalClinical roleExperimental pancreatitisRenalaseAbstractTextERCPPancreatitisFurther studiesAIMSRegression modelsAPOBEC-1 deletion enhances cisplatin-induced acute kidney injury
Guo X, Blanc V, Davidson N, Velazquez H, Chen T, Moledina D, Moeckel G, Safirstein R, Desir G. APOBEC-1 deletion enhances cisplatin-induced acute kidney injury. Scientific Reports 2023, 13: 22255. PMID: 38097707, PMCID: PMC10721635, DOI: 10.1038/s41598-023-49575-3.Peer-Reviewed Original ResearchAltmetricmRNA Editing via the Apobec1 Gene Promotes Recovery from AKI
Guo X, Velazquez H, Xu L, Cheng Z, Chen T, Tian Y, Bewersdorf J, Blanc V, Davidson N, Safirstein R, Desir G. mRNA Editing via the Apobec1 Gene Promotes Recovery from AKI. Journal Of The American Society Of Nephrology 2023, 34: 451-451. DOI: 10.1681/asn.20233411s1451b.Peer-Reviewed Original ResearchRenalase Ameliorates AKI by Altering Mitochondrial Function to Induce Cellular Repair Mechanisms
Guo X, Chen R, Chen T, Safirstein R, Jonas E, Desir G. Renalase Ameliorates AKI by Altering Mitochondrial Function to Induce Cellular Repair Mechanisms. Journal Of The American Society Of Nephrology 2023, 34: 117-117. DOI: 10.1681/asn.20233411s1117b.Peer-Reviewed Original ResearchAn AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model
Charkoftaki G, Aalizadeh R, Santos-Neto A, Tan W, Davidson E, Nikolopoulou V, Wang Y, Thompson B, Furnary T, Chen Y, Wunder E, Coppi A, Schulz W, Iwasaki A, Pierce R, Cruz C, Desir G, Kaminski N, Farhadian S, Veselkov K, Datta R, Campbell M, Thomaidis N, Ko A, Thompson D, Vasiliou V. An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model. Human Genomics 2023, 17: 80. PMID: 37641126, PMCID: PMC10463861, DOI: 10.1186/s40246-023-00521-4.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCOVID-19 patientsDisease severityViral outbreaksFuture viral outbreaksLength of hospitalizationIntensive care unitWorse disease prognosisLife-threatening illnessEffective medical interventionsCOVID-19Clinical decision treeGlucuronic acid metabolitesNew potential biomarkersHospitalization lengthCare unitComorbidity dataSerotonin levelsDisease progressionHealthy controlsPatient outcomesDisease prognosisPatient transferPatientsHealthcare resourcesPotential biomarkersPromoting Collaborative Scholarship During the COVID-19 Pandemic: Creation and Implementation of an Innovative COVID-19 Data Explorer and Repository (DOM- CovX) at Yale School of Medicine (Preprint)
Victoria-Castro A, Arora T, Simonov M, Biswas A, Alausa J, Subair L, Gerber B, Nguyen A, Hsiao A, Hintz R, Yamamoto Y, Soufer R, Desir G, Wilson F, Villanueva M. Promoting Collaborative Scholarship During the COVID-19 Pandemic: Creation and Implementation of an Innovative COVID-19 Data Explorer and Repository (DOM- CovX) at Yale School of Medicine (Preprint). JMIR Formative Research 2023 DOI: 10.2196/52120.Peer-Reviewed Original Research
Academic Achievements and Community Involvement
honor Elected Member
National AwardAmerican Clinical and Climatological AssociationDetails10/28/2019United Stateshonor Community Service Award
Regional AwardSouthern Connecticut Black Nurses AssociationDetails09/13/2019United Stateshonor Trailblazer Award
Regional AwardJamaican American Connection of Greater New HavenDetails09/08/2018United Stateshonor Ground breaker Award
Regional AwardAlpha Phi AlphaDetails09/01/2017United Stateshonor Chi Omicron Chapter, Omega Psi Phi Fraternity
Regional AwardLinks IncDetails09/16/2016United States
Clinical Care
Overview
Gary V. Desir, MD, chair of internal medicine, has pursued his interest in kidney function and disease since earning his medical degree at Yale School of Medicine. The single-minded focus paid off in 2005 when Dr. Desir and fellow researchers discovered renalase, a kidney (renal) protein that plays a role in regulating cardiovascular function.
“A renal fellow and I were caring for patients suffering from kidney disease and cardiovascular-related complications,” Dr. Desir says. “That was the inspiration for looking into the connection between kidney and heart disease. And that search led us to the discovery of renalase.”
At Yale New Haven Hospital, Dr. Desir also serves as the chief of internal medicine. He continues to devote a significant amount of time to kidney research at his lab at the Yale School of Medicine, where he is the Paul B. Beeson Professor of Medicine. An advocate of diversity, Dr. Desir co-founded the Minority Organization for Retention and Expansion (MORE) group at the medical school, with a goal to increase faculty diversity and provide medical students with a growing social network.
Clinical Specialties
Board Certifications
Nephrology
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1986
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1983
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- June 11, 2024
How Can Artificial Intelligence Advance Medical Education and Research to Transform Patient Care?
- June 10, 2024
Drs. Sarita Soares and Bradley Richards New Leaders in Internal Medicine Primary Care Residency
- May 29, 2024
Renalase May Predict Post-ERCP Pancreatitis
- April 05, 2024
Faculty Appointments and Promotions Voting Privileges Expanded in the Academic Clinician Track
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