Lawrence Young, MD
Professor of Medicine (Cardiology) and of Cellular And Molecular PhysiologyCards
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Cardiovascular Medicine
PO Box 208056, 333 Cedar Street
New Haven, CT 06520-8056
United States
About
Titles
Professor of Medicine (Cardiology) and of Cellular And Molecular Physiology
Appointments
Cardiovascular Medicine
ProfessorPrimaryCellular & Molecular Physiology
ProfessorSecondary
Other Departments & Organizations
- Cardiovascular Medicine
- Cellular & Molecular Physiology
- Diabetes Research Center
- Fellowship Training
- Graduate Program in Cellular and Molecular Physiology
- Internal Medicine
- Molecular Medicine, Pharmacology, and Physiology
- Program in Translational Biomedicine (PTB)
- Sports Cardiology Program
- Vascular Biology and Therapeutics Program
- Yale Cardiovascular Research Center (YCVRC)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Medicine
- Yale Ventures
Education & Training
- Fellow
- Yale School of Medicine (1986)
- Resident
- Yale-New Haven Hospital (1983)
- MD
- Yale University (1980)
- AB
- Brown University, Biochemistry (1976)
Research
Overview
Our laboratory is studying the cellular and molecular mechanisms responsible for the metabolic adaptation to the hypoxic stress associated with myocardial ischemia, recently focusing on the AMP-activated protein kinase (AMPK) signaling pathway. AMPK has emerged as a key regulator of glucose transporter (GLUT4) translocation, cellular metabolism, ion channel activity, and cell survival and apoptosis in the heart.
Combining physiologic models of ischemia with cellular and molecular techniques, we are interested in the cardio-protective action of AMPK in the heart, the upstream mechanisms of AMPK activation and its downstream interaction with other signaling pathways, as well as the discovery of novel AMPK targets. The use of transgenic mouse models allows us to dissect the role of AMPK and other signaling pathways in the intact perfused heart and in vivo. The goal of this research is to develop novel strategies to protect the heart against injury during myocardial ischemia.
- Stress signaling pathways is the heart.
- Alterations in metabolism in cardiac disease.
- AMPK as a target for protecting the heart against ischemic injury.
- LKB1 regulation of metabolic signaling and cardic growth.
- Cardiac-derived autocrine-paracrine secreted proteins in the regulation of cardiac signaling pathways.
- Insulin resistance and diabetes in cardiovascular disease.
Medical Research Interests
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Frans Wackers, MD, PhD
Catherine Viscoli, PhD
Walter Kernan, MD
Edward J Miller, MD, PhD
Gerald I Shulman, MD, PhD, MACP, MACE, FRCP
Silvio Inzucchi, MD
AMP-Activated Protein Kinases
Insulin Resistance
Myocardial Ischemia
Glucose Transporter Type 4
Diabetes Mellitus
Apoptosis
Publications
2024
SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts
Goedeke L, Ma Y, Gaspar R, Nasiri A, Lee J, Zhang D, Galsgaard K, Hu X, Zhang J, Guerrera N, Li X, LaMoia T, Hubbard B, Haedersdal S, Wu X, Stack J, Dufour S, Butrico G, Kahn M, Perry R, Cline G, Young L, Shulman G. SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts. Journal Of Clinical Investigation 2024, 134: e176708. PMID: 39680452, PMCID: PMC11645152, DOI: 10.1172/jci176708.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsSodium-glucose cotransporter type 2Heart failureKetone oxidationGas chromatography-mass spectrometryFatty acid oxidationLeft ventricular ejection fractionReduced myocardial oxidative stressVentricular ejection fractionKetone supplementationWeeks of treatmentMyocardial oxidative stressDecreased pyruvate oxidationInduce heart failurePlasma glucose levelsIn vivo effectsSGLT2i treatmentEjection fractionAssociated with improvementsAwake ratsSGLT2 inhibitionCardioprotective benefitsLiquid chromatography-tandem mass spectrometryPlasma ketonesRates of ketonizationChromatography-tandem mass spectrometryMitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction
Rudokas M, McKay M, Toksoy Z, Eisen J, Bögner M, Young L, Akar F. Mitochondrial network remodeling of the diabetic heart: implications to ischemia related cardiac dysfunction. Cardiovascular Diabetology 2024, 23: 261. PMID: 39026280, PMCID: PMC11264840, DOI: 10.1186/s12933-024-02357-1.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsReactive oxygen speciesMitochondrial network remodelingDamaged mitochondrial DNAEfficiency of oxidative phosphorylationImpaired ATP productionMitochondrial ultrastructural alterationsCardiac functionDiabetic heartCellular energy metabolismProduction of reactive oxygen speciesMitochondrial DNAMitochondrial networkMitochondrial fissionExcessive production of reactive oxygen speciesOxidative phosphorylationATP productionResponse to ischemic insultGlobal cardiac functionCell deathOverall cardiac functionCardiac ischemic injuryResponse to injuryCardiac mitochondriaIrreversible cell deathMitochondriaDownregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia
Huang Y, Chen L, Li L, Qi Y, Tong H, Wu H, Xu J, Leng L, Cheema S, Sun G, Xia Z, McGuire J, Rodrigues B, Young L, Bucala R, Qi D. Downregulation of adipose LPL by PAR2 contributes to the development of hypertriglyceridemia. JCI Insight 2024, 9: e173240. PMID: 38973609, PMCID: PMC11383372, DOI: 10.1172/jci.insight.173240.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsMacrophage migration inhibitory factorDevelopment of hypertriglyceridemiaWhite adipose tissueAdipose LPLPAR2 expressionLevels of macrophage migration inhibitory factorElevated plasma TG levelsLPL expressionLipoprotein lipaseIncrease PAR2 expressionPlasma MIF levelsPlasma TG levelsMigration inhibitory factorPalmitic acid dietInhibited Akt phosphorylationMIF levelsLipoprotein lipase geneTG levelsObese humansPlasma TGHypertriglyceridemiaAkt phosphorylationLipid storageInhibitory factorAdipose tissueLDL Receptor-Related Protein 5 Selectively Transports Unesterified Polyunsaturated Fatty Acids to Intracellular Compartments
Tang W, Luan Y, Yuan Q, Li A, Chen S, Menacherry S, Young LH, and Wu D; Nature CommunicationsPeer-Reviewed Original Research In Press
2023
An explainable machine learning-based phenomapping strategy for adaptive predictive enrichment in randomized clinical trials
Oikonomou E, Thangaraj P, Bhatt D, Ross J, Young L, Krumholz H, Suchard M, Khera R. An explainable machine learning-based phenomapping strategy for adaptive predictive enrichment in randomized clinical trials. Npj Digital Medicine 2023, 6: 217. PMID: 38001154, PMCID: PMC10673945, DOI: 10.1038/s41746-023-00963-z.Peer-Reviewed Original ResearchExtracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity
Chen L, Li L, Cui D, Huang Y, Tong H, Zabihi H, Wang S, Qi Y, Lakowski T, Leng L, Liu S, Wu H, Young L, Bucala R, Qi D. Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity. Molecular Metabolism 2023, 79: 101834. PMID: 37935315, PMCID: PMC10700858, DOI: 10.1016/j.molmet.2023.101834.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorExtracellular MIFHigh-fat dietHormone-sensitive lipaseDevelopment of obesityMigration inhibitory factorInhibitory factorRole of cytokinesExtracellular actionJNK phosphorylationMIF levelsSevere obesityHFD miceHFD feedingMIF antibodyWT miceAdipocyte hypertrophyCOP9 signalosome subunit 5Fat dietHSL expressionObesityAutocrine fashionHSL activationSensitive lipaseInhibitory actionIntra-Aortic Balloon Pump Exacerbates Left Ventricular Outflow Tract Obstruction in a Patient With Takotsubo and Hypertrophic Cardiomyopathy
Griffin M, Odanovic N, McNamara R, Altin S, Balan S, Thompson J, Young L. Intra-Aortic Balloon Pump Exacerbates Left Ventricular Outflow Tract Obstruction in a Patient With Takotsubo and Hypertrophic Cardiomyopathy. Case 2023, 7: 502-507. PMID: 38197115, PMCID: PMC10772928, DOI: 10.1016/j.case.2023.07.003.Peer-Reviewed Original ResearchA pref-1-controlled non-inflammatory mechanism of insulin resistance
Huang Y, Cui D, Chen L, Tong H, Wu H, Muller G, Qi Y, Wang S, Xu J, Gao X, Fifield K, Wang L, Xia Z, Vanderluit J, Liu S, Leng L, Sun G, McGuire J, Young L, Bucala R, Qi D. A pref-1-controlled non-inflammatory mechanism of insulin resistance. IScience 2023, 26: 106923. PMID: 37283810, PMCID: PMC10239698, DOI: 10.1016/j.isci.2023.106923.Peer-Reviewed Original ResearchConceptsInsulin resistanceMIF secretionPref-1 expressionPref-1Fat-induced insulin resistancePlasma MIF levelsNon-inflammatory mechanismsActivation of PAR2Palmitic acid dietHigh fat-induced insulin resistanceWhite adipose tissueSubsequent insulin resistanceMIF levelsPAR2 expressionM2 macrophagesAcid dietAdipose tissueAMPK-dependent mannerEndothelial cellsSecretionIntegrin β1CellsExpressionHigh levelsInflammationA Case of Fulminant Right Heart Failure Owing to Tumoral Pulmonary Hypertension
Wang K, Verma A, Fish K, Hu J, Miller P, Morrow J, Singh I, Young L. A Case of Fulminant Right Heart Failure Owing to Tumoral Pulmonary Hypertension. JACC Case Reports 2023, 10: 101715. PMID: 36974052, PMCID: PMC10039392, DOI: 10.1016/j.jaccas.2022.101715.Peer-Reviewed Case Reports and Technical NotesRole of AMPK pathway inactivation in high fat diet related cardiac electrophysiological remodeling
Rudokas M, Cacheux M, Wu X, Hummel M, Young L, Akar F. Role of AMPK pathway inactivation in high fat diet related cardiac electrophysiological remodeling. Biophysical Journal 2023, 122: 380a-381a. DOI: 10.1016/j.bpj.2022.11.2089.Peer-Reviewed Original Research
Academic Achievements & Community Involvement
activity J Mol Cell Cardiology
Journal ServiceReviewerDetails03/01/2017 - Presentactivity Yale NIH Diabetes Research Center
Peer Review Groups and Grant Study SectionsGrant ReviewerDetails2024 - 2024activity Metabolic Stress and Atrial Fibrillation
Oral PresentationYale Vascular Biology and Therapeutics Annual Scientific SymposiumDetails11/16/2023 - PresentNew Haven, CT, United Statesactivity Metabolic stress and the heart: From ischemia to arrhythmia
LectureYale Endoocrine Grand RoundsDetails05/26/2023 - PresentNew Haven, CT, United Stateshonor Best Doctors in America (Cardiology)
National AwardDetails06/01/2020, 06/01/2019, 06/01/2018, 06/01/2017, 06/01/2016, 06/01/2015, 06/01/2014, 06/01/2013, 06/01/2012, 06/01/2011, 06/01/2010, 06/01/2009, 06/01/2008, 06/01/2007, 06/01/2006, 06/01/2005, 06/01/2004, 06/01/2003, 06/01/2002, 06/01/2001, 06/01/2000, 06/01/1999, 06/01/1998United States
Clinical Care
Overview
Lawrence H. Young, MD, is a cardiologist who treats patients suffering from heart conditions, both complex and common. With more than 30 years of experience, Dr. Young also specializes in diagnosing and treating patients with a rare genetic disease called hereditary hemorrhagic telangiectasia (HHT). "Yale is probably the world's leader in understanding and treating patients with HHT," Dr. Young says. HHT is a rare genetic disorder that causes abnormal blood vessel growth and heart failure.
As an intern, Dr. Young spent time treating cardiac patients in the cardiac intensive care unit and "decided then and there I wanted to be a cardiologist," he says. "I enjoy taking care of acutely ill patients, but I also enjoy seeing patients over time and helping them to stay healthy."
At the Yale School of Medicine, Dr. Young is a professor of medicine. He leads an active research group, investigating the intersection of heart health and diabetes.
Clinical Specialties
Fact Sheets
Hereditary Hemorrhagic Telangiectasia (HHT)
Learn More on Yale MedicineAVNeo (Aortic valve neocuspidization, Ozaki Procedure)
Learn More on Yale MedicineHeart Disease in Women
Learn More on Yale MedicinePulmonary Edema
Learn More on Yale Medicine
Board Certifications
Cardiovascular Disease
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1985
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1983
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News
- April 05, 2024
Faculty Appointments and Promotions Voting Privileges Expanded in the Academic Clinician Track
- January 09, 2024
Recap & Reflections: Vascular Biology & Therapeutics Program & Cardiovascular Research Center 2023 Retreat
- March 28, 2023
Appointments & Promotions Committee Facilitates Faculty Success
- February 26, 2023
Meet Yale Internal Medicine’s Faculty Affairs Team
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Contacts
Cardiovascular Medicine
PO Box 208056, 333 Cedar Street
New Haven, CT 06520-8056
United States
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Are You a Patient? View this doctor's clinical profile on the Yale Medicine website for information about the services we offer and making an appointment.