Adjunct faculty typically have an academic or research appointment at another institution and contribute or collaborate with one or more School of Medicine faculty members or programs.
Adjunct rank detailsMark Sleeman, PhD
About
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Biography
Dr Sleeman has a combined background in neurobiology, endocrinology and biochemistry and he has published in journals such PNAS, Cell Metabolism and Nature Medicine, Genetics and Neuroscience. He is a leader within the field of metabolic research and his work has often challenged established theories in insulin signaling and diabetes (role of ChREBP, SHIP2 and Trb3) and at other times been seminal in expanding fields of research, such as for gut peptide ghrelin. Common to all studies is the combined use of mouse and human genomic approaches, gene expression analysis coupled with detailed physiological studies to understand primary mechanism of action. His leadership qualities are evident by the ability to simultaneously lead a discover research and therapeutic development team in a world-class biotechnology company.
Appointments
Comparative Medicine
Professor AdjunctPrimary
Other Departments & Organizations
Education & Training
- PhD
- Monash University (1989)
Research
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Overview
Dr. Sleeman is the Head of Metabolic Research at Regeneron Pharmaceuticals in Tarrytown, New York. For the past two decades he has been interested in the interplay between insulin resistance and obesity, and more specifically the molecular mechanisms behind the regulation food intake and body weight. Recently, his research has focused on the role that gut hormones such as ghrelin and PYY play in signaling to a number of brain regions to modulate metabolic events. To that end he and his colleagues have generated a large number of genetically modified animals to study these phenotypes. Ultimately, his work may clarify the complex relationships on the role that circulating hormones play in regulation of short and long term metabolic events such as bone and mineral metabolism and food intake&body weight control.
Mark Sleeman was a recipient of a Juveniles Diabetes and Ruth Kirschstein Endocrine Fellowship at the University of Massachusetts in the laboratory of Dr Michael P. Czech where he studied mechanisms insulin-resistance/signaling. Dr Sleeman received his Ph.D. from Monash University, Australia, where he specialized in neurobiology and has published numerous papers in Type 2 Diabetes and Obesity in journals such as Nature Medicine, Nature Genetics, PNAS, Journal of Biological Chemistry and Diabetes and is a member of numerous professional societies in US.
ORCID
0000-0002-3329-0919
Research at a Glance
Yale Co-Authors
Publications Timeline
Tamas Horvath, DVM, PhD
Tormod Rogne, MD, PhD
Publications
2025
Combined endurance and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults
Stec M, Graham Z, Su Q, Adler C, Ni M, Le Rouzic V, Golann D, Ferrara P, Halasz G, Sleeman M, Lavin K, Broderick T, Bamman M. Combined endurance and resistance exercise training alters the spatial transcriptome of skeletal muscle in young adults. IScience 2025, 28: 113301. PMID: 40894879, PMCID: PMC12398908, DOI: 10.1016/j.isci.2025.113301.Peer-Reviewed Original ResearchCitationsAltmetricConceptsExercise trainingEndurance exercise trainingResistance exercise trainingChronic exercise trainingMuscle function improvementSkeletal muscle functionCombined enduranceExercise-induced shiftsNeuromuscular recruitmentExercise boutMuscle adaptationHuman muscleMuscle functionFiber type specificitySpatial transcriptomicsFunctional improvementYoung adultsTranscriptome of skeletal muscleEnduranceGene expression changesMuscleSingle cell RNAseq dataTrainingSkeletal muscleCell populationsGDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates
Mastaitis J, Gomez D, Raya J, Li D, Min S, Stec M, Kleiner S, McWilliams T, Altarejos J, Murphy A, Yancopoulos G, Sleeman M. GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates. Nature Communications 2025, 16: 4377. PMID: 40360507, PMCID: PMC12075787, DOI: 10.1038/s41467-025-59485-9.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGlucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsReceptor agonistsA blockadeGlucagon-like peptide-1 receptor agonist treatmentMuscle lossMuscle massFat lossObese male miceNon-human primatesType II activin receptorTreatment of obesityQuality of weight lossSignificant muscle lossIncrease muscle massEnhanced fat lossAgonist treatmentMale miceMuscle preservationAppetite suppressionActivin AActivin receptorsObese miceCaloric restrictionWeight lossGDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial
Gonzalez Trotter D, Donahue S, Wynne C, Ali S, Parasoglou P, Boyapati A, Mohammadi K, Musser B, Meier P, Mastaitis J, Sleeman M, Glass D, Gasparino E, Trejos J, Davis J, Hirshberg B, Pordy R, Yancopoulos G, Herman G. GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial. Nature Communications 2025, 16: 4376. PMID: 40360471, PMCID: PMC12075688, DOI: 10.1038/s41467-025-59380-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHealthy postmenopausal femalesNegative regulator of muscle massRegulation of muscle massMultiple-dose partMultiple-dose administrationRegional body compositionPostmenopausal femalesMuscle massThigh muscle volumeDominant negative regulatorDose combinationSeverity of treatment-emergent adverse eventsPlacebo-controlled phase 1 trialActivin APresence of anti-drug antibodiesRandomized phase I trialTreatment-emergent adverse eventsBody compositionDual X-ray absorptiometrySingle-dose partPhase I trialPhase 1 trialSingle-dose administrationX-ray absorptiometryAnti-drug antibodiesHepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk
Bao K, Berger J, Na E, Su Q, Halasz G, Sleeman M, Okamoto H. Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk. Diabetes 2025, 74: 885-897. PMID: 40095004, PMCID: PMC12097458, DOI: 10.2337/db24-0958.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsAmino acid catabolismGlucagon receptorControlling amino acid metabolismDownstream effectorsGlucagon receptor blockadeA cellsElevated plasma amino acidsAmino acidsAlpha cell massPlasma amino acidsCatabolism of amino acidsPKA knockdownAmino acid metabolismGlucagon-stimulated hepatic glucose productionCatabolic genesGcgr signalingPancreatic A cellsEPAC2 knockdownGNASHyperplasiaHepatic glucose productionDownstream factorsAcid metabolismCell massEpac2Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
Su Q, Kim S, Adewale F, Zhou Y, Aldler C, Ni M, Wei Y, Burczynski M, Atwal G, Sleeman M, Murphy A, Xin Y, Cheng X. Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver. IScience 2025, 28: 111951. PMID: 39995867, PMCID: PMC11848438, DOI: 10.1016/j.isci.2025.111951.Peer-Reviewed Original ResearchConcepts
2024
Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes
Zhou Y, Stevis P, Cao J, Ehrlich G, Jones J, Rafique A, Sleeman M, Olson W, Franklin M. Structures of complete extracellular assemblies of type I and type II Oncostatin M receptor complexes. Nature Communications 2024, 15: 9776. PMID: 39532904, PMCID: PMC11557873, DOI: 10.1038/s41467-024-54124-1.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsLeukemia inhibitory factor receptorOncostatin MExtracellular assemblyReceptor complexOSM receptorOncostatin M signalingOncostatin M receptorJuxtamembrane domainGp130 bindingCryogenic electron microscopyStructural basisGlycoprotein 130Cryo-EMFamily cytokinesBiological eventsGp130Therapeutic targetComplex formationFactor receptorType IMouse typesReceptorsAssemblyJuxtamembraneMutagenesisEffect of IL-6R blockade on plasma lipids and clinical outcomes among hospitalized patients with COVID-19 infection
Mohammadi K, Sleeman M, Boyapati A, Bigdelou P, Geba G, Fazio S. Effect of IL-6R blockade on plasma lipids and clinical outcomes among hospitalized patients with COVID-19 infection. Journal Of Lipid Research 2024, 65: 100568. PMID: 38795859, PMCID: PMC11237931, DOI: 10.1016/j.jlr.2024.100568.Peer-Reviewed Original ResearchCitationsConceptsPlasma lipid changesIL-6R blockadePlasma lipid levelsCOVID-19 pneumoniaClinical outcomesLDL-CHDL-CLipid levelsLipid changesSystemic infectionIL-6-mediated inflammationDay 7Moderately elevated triglyceridesInfluence plasma lipid levelsBaseline lipid levelsLDL-C levelsAbnormal lipid levelsAnti-inflammatory interventionsIL-6RLower LDL-CAcute systemic infectionNo significant associationPost Hoc AnalysisInterleukin-6 receptorStudy therapyLoss of murine Gpr45 leads to significant obesity due to hyperphagia and hypoactivity
Mumal I, Min S, Lee D, Trenish J, Pryce D, Gomez D, Na E, Bigdelou P, Altarejos J, Sleeman M, Mastaitis J. Loss of murine Gpr45 leads to significant obesity due to hyperphagia and hypoactivity. Endocrine Abstracts 2024 DOI: 10.1530/endoabs.99.oc12.1.Peer-Reviewed Original ResearchDifferential Regulation of the Type 2 Cytokines, IL-4 and IL-13, and the Alarmins, IL-33 and TSLPA, in Airway Inflammation and Remodeling
Asrat S, Srivatsan S, Buonagurio B, Nagashima K, Scott G, Gayvert K, Lim W, Ben L, Le Floc’h A, Murphy A, Sleeman M, Orengo J. Differential Regulation of the Type 2 Cytokines, IL-4 and IL-13, and the Alarmins, IL-33 and TSLPA, in Airway Inflammation and Remodeling. 2024, a3276-a3276. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a3276.Peer-Reviewed Original ResearchThe High Affinity Anti-IL-33 Antibody Itepekimab Potently Blocks IL-33 Induced Activation of the ST2/IL-1RAcP Signaling Complex and Inhibits Key Mediators of Airway Inflammation
Asrat S, Zhou Y, Rafique A, Kamat V, Scott G, Birchard D, Ben L, Murphy A, Franklin M, Sleeman M, Orengo J. The High Affinity Anti-IL-33 Antibody Itepekimab Potently Blocks IL-33 Induced Activation of the ST2/IL-1RAcP Signaling Complex and Inhibits Key Mediators of Airway Inflammation. 2024, a6989-a6989. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a6989.Peer-Reviewed Original Research