Nancy J. Brown, MD
Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal MedicineCards
Publications Overview
- 295 Publications
- 15,880 Citations
- 3 Yale Co-Authors
Contact Info
Office of the Dean, School of Medicine
333 Cedar Street
New Haven, CT 06510
United States
Administrative Support
Publications Overview
- 295 Publications
- 15,880 Citations
- 3 Yale Co-Authors
Contact Info
Office of the Dean, School of Medicine
333 Cedar Street
New Haven, CT 06510
United States
Administrative Support
Publications Overview
- 295 Publications
- 15,880 Citations
- 3 Yale Co-Authors
Contact Info
Office of the Dean, School of Medicine
333 Cedar Street
New Haven, CT 06510
United States
About
Titles
Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal Medicine
Biography
Nancy J. Brown, M.D. is the Jean and David W. Wallace Dean of Yale School of Medicine and the C.N.H. Long professor of Internal Medicine. Prior to coming to Yale, Dr. Brown served as chair of the Vanderbilt Department of Medicine and physician-in-chief of Vanderbilt University Medical Center from 2010 to 2020.
Dr. Brown's research has focused on the mechanisms through which the renin-angiotensin-aldosterone, kallikrein-kinin, and incretin systems affect inflammation, thrombosis, metabolism and cardiovascular risk. Her lab defined the contribution of endogenous bradykinin to fibrinolysis in humans and the prothrombotic and fibrotic effects of aldosterone mediated by plasminogen activator inhibitor-1. Her research group identified African ancestry and specific genetic variants as risk factors for angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. Ongoing research in the laboratory focuses on the mechanism(s) of combined angiotensin receptor blocker (ARB)/neprilysin inhibitors in heart failure as well as on the cardiovascular effects of incretin-based anti-diabetic therapies.
As a clinician, Dr. Brown's specializes in the diagnosis and treatment of resistant hypertension; since coming to Yale, she has volunteered in the student-run HAVEN clinic. Throughout her career, Dr. Brown has worked to promote the development of physician-scientists. She established the Vanderbilt Master of Science in Clinical Investigation in 2000. From 2006-2010, she served as the Associate Dean for Clinical and Translational Scientist Development at Vanderbilt and established an institutional infrastructure to support physician-scientists in the transition to independence.
Dr. Brown served on the NIH National Advisory Research Resources Council and the National Heart, Lung, and Blood Advisory Council. Her research has been recognized by the Harriet Dustan Award from the American Heart Association, the E.K. Frey-E. Werle Foundation, the August M. Watanabe Prize in Translational Research, and others. In 2018, she was named the Robert H. Williams, MD, Distinguished Chair of Medicine by the Association of Professors of Medicine.
Dr. Brown is a fellow in the American Association for the Advancement of Science and a member of the American Society for Clinical Investigation, the American Association of Physicians, the American Clinical and Climatological Association, the National Academy of Medicine, and the American Academy of Arts and Sciences.
Appointments
Office of the Dean, School of Medicine
DeanDualInternal Medicine
ProfessorPrimary
Other Departments & Organizations
Education & Training
- Chief Resident
- Vanderbilt University (1992)
- Fellow in Clinical Pharmacology
- Vanderbilt University (1991)
- Medicine Intern and Resident
- Vanderbilt University (1989)
- MD
- Harvard University (1986)
- Development Scientist
- Energy Resources Company, Inc. (1982)
- AB
- Yale College, Molecular Biophysics and Biochemistry (1981)
Board Certifications
Internal Medicine
- Certification Organization
- AB of Internal Medicine
- Original Certification Date
- 1989
Research
Overview
The renin-angiotensin-aldosterone system (RAAS) is one of the major blood pressure regulating systems in the body. The small peptide angiotensin II, Ang II, raises blood pressure by constricting blood vessels and increasing salt retention, in part by stimulating synthesis of the mineralocorticoid aldosterone. Studies in our laboratory have examined how Ang II and aldosterone cause inflammation and fibrosis, promote clotting and affect the risk of diabetes.
Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRAs) are classes of drugs that interrupt the RAAS. ACE inhibitors decrease formation of Ang II whereas ARBs block the effect of Ang II at its major receptor and MRAs block the effects of aldosterone. ACE inhibitors also prevent the breakdown of bradykinin, a peptide in the body that lowers blood pressure and causes salt excretion.
We have shown that bradykinin has other beneficial effects, like increasing release of tissue-type plasminogen activator from the vascular endothelium. Bradykinin can also have detrimental effects, promoting inflammation. The net beneficial or detrimental effect of bradykinin may depend on the health of the blood vessels. Neprilysin inhibitors, combined with an ARB in the heart failure drug sacubitril/valsartan, also affect the breakdown of bradykinin and other vasoactive peptides such as substance P. We are currently studying how bradykinin and substance P contribute to the effects of sacubitril/valsartan.
Despite the many beneficial effects of ACE inhibitors, this class of medications can cause swelling of the lips, tongue, or face, a side effect called angioedema. Likely, this side effect results from decreased breakdown of bradykinin and another peptide called substance P. We have determined groups of patients who are at increased risk for angioedema. Studies in our laboratory have identified genetic variants in pathways involved in angioedema, allowing us to better predict risk and prevent the side effect.
Another class of drugs that affects the breakdown of substance P as well as the incretin hormones like glucagon-like peptide-1 (GLP-1) are the dipeptidyl peptidase-4 (DPP4) inhibitors such as sitagliptin (Janvuia).
Over the last several years, we have been studying the differing effects of DPP4 inhibitors and GLP-1 agonists such as liraglutide (Victoza and Saxenda) or semaglutide (brand names Ozempic, Wegovy, and Rybelsus) the cardiovascular function.
Medical Research Interests
ORCID
0000-0001-7109-3142
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Emmanuel Akintoye, MD, MPH
Harlan Krumholz, MD, SM
Jeffrey Testani, MD, MTR
Angiotensin-Converting Enzyme Inhibitors
Hypertension
Bradykinin
Renin-Angiotensin System
Fibrinolysis
Angioedema
Publications
2024
The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose
Mashayekhi M, Sheng Q, Bailin S, Massier L, Zhong J, Shi M, Wanjalla C, Wang T, Ikizler T, Niswender K, Gabriel C, Palacios J, Turgeon‐Jones R, Reynolds C, Luther J, Brown N, Das S, Dahlman I, Mosley J, Koethe J, Rydén M, Bachmann K, Shah R. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose. Obesity 2024, 32: 1526-1540. PMID: 38967296, PMCID: PMC11269023, DOI: 10.1002/oby.24064.Peer-Reviewed Original ResearchConceptsVisceral adipose tissueExpression quantitative trait lociSubcutaneous adipose tissueGenetic effect sizesQuantitative trait lociInsulin resistanceAdipocyte transcriptsSat geneAdipose transcriptomeTrait lociTranscriptional architectureTranscriptional landscapeMetabolic bufferRNA sequencingInsulin stimulationAdipose tissueNon-immune cell populationsMetabolic phenotypeWeight loss surgeryNon-immune populationSpectrum of obesityCardiometabolic disease riskMacrophage transcriptionMolecular signaturesType 2 diabetes
2023
Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes.
Mashayekhi M, Nian H, Mayfield D, Devin J, Gamboa J, Yu C, Silver H, Niswender K, Luther J, Brown N. Weight Loss-Independent Effect of Liraglutide on Insulin Sensitivity in Individuals With Obesity and Prediabetes. Diabetes 2023, 73: 38-50. PMID: 37874653, PMCID: PMC10784656, DOI: 10.2337/db23-0356.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsEndogenous GLP-1Glucagon-like peptide-1 receptor agonistsPeptide-1 receptor agonistsImproved insulin sensitivityInsulin sensitivityGLP-1GLP-1RGlucagon levelsGlucose levelsMatsuda indexWeight lossHypocaloric dietPostprandial glucoseInhibitor sitagliptinReceptor agonistMetabolic effectsDiet-induced weight lossDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent effectsDPP-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitionPeptidase-4 inhibitionMixed meal testGLP-1R antagonistEffect of the glucagon‐like peptide‐1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes
Silver H, Olson D, Mayfield D, Wright P, Nian H, Mashayekhi M, Koethe J, Niswender K, Luther J, Brown N. Effect of the glucagon‐like peptide‐1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes. Diabetes Obesity And Metabolism 2023, 25: 2340-2350. PMID: 37188932, PMCID: PMC10544709, DOI: 10.1111/dom.15113.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAdultAppetiteBody Fat DistributionBody WeightCaloric RestrictionCardiovascular DiseasesDiabetes Mellitus, Type 2Dipeptidyl-Peptidase IV InhibitorsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesEatingGlucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsLiraglutideObesityPrediabetic StateSitagliptin PhosphateWeight LossConceptsGlucagon-like peptide-1 receptor agonist liraglutidePeptide-1 receptor agonist liraglutideLiraglutide groupSitagliptin groupCR groupCaloric restrictionChi-squared testDietary intakeWeight lossBody weightBody compositionDipeptidyl peptidase-4 inhibitor sitagliptinDipeptidyl peptidase-4 inhibitorsDual-energy X-ray absorptiometryEnergy X-ray absorptiometryInsulin resistance scoreBaseline body weightHomeostatic model assessmentPeptidase-4 inhibitorsCardiometabolic risk reductionBody fat distributionVisual analog scaleWeeks of interventionPersonal risk factorsX-ray absorptiometryBradykinin B2 receptor blockade and intradialytic hypotension
Gamboa J, Mambungu C, Clagett A, Nian H, Yu C, Ikizler T, Brown N. Bradykinin B2 receptor blockade and intradialytic hypotension. BMC Nephrology 2023, 24: 134. PMID: 37170244, PMCID: PMC10176680, DOI: 10.1186/s12882-023-03192-4.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsBradykinin B2 receptor blockadeB2 receptor blockadeMaintenance hemodialysisBlood pressureReceptor blockersReceptor blockadeIntradialytic hypotensionBradykinin B2 receptor blockerLack of vasoconstrictionProduction of vasodilatorsSystolic blood pressureGroup of patientsCrossover clinical trialCommon clinical complicationHemodynamic effectsClinical complicationsContinuous infusionClinical trialsStratified analysisIcatibantHemodialysisPatientsHypotensionPlaceboCompensatory mechanismsObesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network
Clark J, Garvey W, Niswender K, Schmidt A, Ahima R, Aleman J, Battarbee A, Beckman J, Bennett W, Brown N, Chandler‐Laney P, Cox N, Goldberg I, Habegger K, Harper L, Hasty A, Hidalgo B, Kim S, Locher J, Luther J, Maruthur N, Miller E, Sevick M, Wells Q. Obesity and Overweight: Probing Causes, Consequences, and Novel Therapeutic Approaches Through the American Heart Association's Strategically Focused Research Network. Journal Of The American Heart Association 2023, 12: e027693. PMID: 36752232, PMCID: PMC10111504, DOI: 10.1161/jaha.122.027693.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsAmerican Heart AssociationHeart AssociationWeight loss interventionNovel therapeutic approachesVanderbilt University Medical CenterUniversity Medical CenterEffective therapeutic interventionsField of obesityResearch NetworkLoss interventionClinical trialsWorldwide prevalenceMedical CenterTherapeutic approachesObesityTherapeutic targetAnimal modelsJohns Hopkins University SchoolTherapeutic interventionsIndividual centersNew targetsUniversity of AlabamaOverweightUniversity SchoolInterventionCancer Therapy–Related Hypertension: A Scientific Statement From the American Heart Association
Cohen J, Brown N, Brown S, Dent S, van Dorst D, Herrmann S, Lang N, Oudit G, Touyz R, Arteriosclerosis T. Cancer Therapy–Related Hypertension: A Scientific Statement From the American Heart Association. Hypertension 2023, 80: e46-e57. PMID: 36621810, PMCID: PMC10602651, DOI: 10.1161/hyp.0000000000000224.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsCardiovascular toxicityVascular endothelial growth factor inhibitorsCancer therapyEvidence-based clinical trialsNational hypertension guidelinesVascular endothelial growth factor receptorCardiovascular risk factorsDiscontinuation of treatmentCommon side effectsGrowth factor inhibitorsEndothelial growth factor receptorPrimary care professionalsAmerican Heart AssociationTyrosine kinase inhibitorsOptimal therapeutic effectNitric oxide generationGrowth factor receptorHypertension specialistsHypertension guidelinesSympathetic outflowAdjunctive therapyCardiovascular mortalityEndothelial dysfunctionHormone therapyBlood pressure
2022
Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial
Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin‐based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obesity And Metabolism 2022, 25: 570-580. PMID: 36306151, PMCID: PMC10306232, DOI: 10.1111/dom.14903.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsFlow-mediated vasodilationPlasminogen activator inhibitor-1Vascular endothelial functionEndothelial functionInsulin resistanceWeight lossGlucagon-like peptide-1 receptor agonistsBaseline flow-mediated vasodilationDipeptidyl peptidase-4 inhibitor sitagliptinGLP-1R agonist liraglutideWeight loss-independent mechanismsPeptide-1 receptor agonistsBeneficial effectsEndothelial vasodilator functionGreater endothelial dysfunctionIncretin-based therapiesNormal endothelial functionChemoattractant protein-1Chemokine MCP-1Significant weight lossActivator inhibitor-1Effect of treatmentVasodilator functionUrine albuminEndothelial dysfunctionComparison of Pharmacy Refill Data With Chemical Adherence Testing in Assessing Medication Nonadherence in a Safety Net Hospital Setting
Osula D, Wu B, Schesing K, Das SR, Moss E, Alvarez K, Clark C, Halm EA, Brown NJ, Vongpatanasin W. Comparison of Pharmacy Refill Data With Chemical Adherence Testing in Assessing Medication Nonadherence in a Safety Net Hospital Setting. Journal Of The American Heart Association 2022, 11: e027099. PMID: 36193931, PMCID: PMC9673714, DOI: 10.1161/jaha.122.027099.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsMeSH KeywordsAdrenergic beta-AntagonistsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsCalcium Channel BlockersCross-Sectional StudiesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypertensionMedication AdherencePharmacySafety-net ProvidersSodium Chloride Symporter InhibitorsConceptsEnzyme inhibitors/angiotensin receptor blockersAngiotensin receptor blockersCalcium channel blockersReceptor blockersPositive predictive valueUncontrolled hypertensionBeta blockersMedication nonadherenceAntihypertensive drugsDrug classesChannel blockersAngiotensin-converting enzyme inhibitors/angiotensin receptor blockersPredictive valueAdherence testingSafety-net hospital settingSafety-net health systemLow positive predictive valuePharmacy refill dataProportion of daysCross-sectional studyPlasma drug levelsDiagnostic test characteristicsPharmacy fill dataCommon cardiovascular drugsRefill dataProneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma
Eugster PJ, Maurer J, Vocat C, Abid K, Matter M, Wuerzner G, Trepp R, Fischli S, Henzen C, Kolb W, Bilz S, Sigrist S, Beuschlein F, Nölting S, Reul A, Schütze I, Hubers SA, Brown NJ, Grouzmann E. Proneuropeptide Y and neuropeptide Y metabolites in healthy volunteers and patients with a pheochromocytoma or paraganglioma. Clinica Chimica Acta 2022, 534: 146-155. PMID: 35905838, DOI: 10.1016/j.cca.2022.07.018.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsUpper reference limitPlasma free metanephrinesNeuropeptide YSevere kidney impairmentFree metanephrinesNPY3-36Kidney impairmentSympathetic nervesCatecholamine reuptakeVasoconstrictor peptideNPY2-36NPY1-36Early diagnosisHealthy volunteersPPGL patientsAdrenal medullaTumor localizationPatientsNPYReference limitsDiagnostic sensitivityPPGLsGold standardReference intervalsPheochromocytomaGlucagon-Like Peptide-1 Receptor Regulates Thromboxane-Induced Human Platelet Activation
Cahill KN, Amin T, Boutaud O, Printz R, Newcomb DC, Foer D, Hodson DJ, Broichhagen J, Beckman JA, Yu C, Nian H, Mashayekhi M, Silver HJ, Luther JM, Brown NJ, Peebles RS, Niswender K. Glucagon-Like Peptide-1 Receptor Regulates Thromboxane-Induced Human Platelet Activation. JACC Basic To Translational Science 2022, 7: 713-715. PMID: 35958685, PMCID: PMC9357570, DOI: 10.1016/j.jacbts.2022.04.004.Peer-Reviewed Original Research
Clinical Trials
Current Trials
Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 3
HIC ID2000028712RolePrincipal InvestigatorPrimary Completion Date12/31/2025Recruiting Participants
Academic Achievements & Community Involvement
honor August M. Watanabe Prize in Translational Research
National AwardIndiana University School of MedicineDetails09/24/2021United Stateshonor Fellow
International AwardRoyal College of PhysiciansDetails09/01/2021United Kingdomhonor Elected Member to the American Academy of Arts & Sciences
National AwardAmerican Academy of Arts & SciencesDetails04/26/2021United Stateshonor Elected Master
National AwardAmerican College of PhysiciansDetails01/01/2019United Stateshonor A. Ross McIntyre Award for Achievement in Medical Science
National AwardUniversity of Nebraska College of MedicineDetails01/01/2018United States
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- December 11, 2024
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- November 21, 2024
Three Yale School of Medicine-led Teams Awarded $18 Million to Advance Parkinson’s Disease Research
- November 13, 2024
YSM Faculty Receive Awards for Innovation
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333 Cedar Street
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United States
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