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Nancy J. Brown, MD

Jean and David W. Wallace Dean of the Yale School of Medicine and C.N.H. Long Professor of Internal Medicine
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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

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 Subject Headings (MeSH)

Angioedema; Angiotensin-Converting Enzyme Inhibitors; Atrial Fibrillation; Bradykinin; Fibrinolysis; Hypertension; Inflammation; Renin-Angiotensin System

Research at a Glance

Yale Co-Authors

Frequent collaborators of Nancy J. Brown's published research.

Publications

2024

2023

2022

Clinical Trials

Current Trials

Academic Achievements & Community Involvement

  • honor

    August M. Watanabe Prize in Translational Research

  • honor

    Fellow

  • honor

    Elected Member to the American Academy of Arts & Sciences

  • honor

    Elected Master

  • honor

    A. Ross McIntyre Award for Achievement in Medical Science

Get In Touch

Contacts

Academic Office Number
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Mailing Address

Office of the Dean, School of Medicine

333 Cedar Street

New Haven, CT 06510

United States

Administrative Support

Events

Oct 202422Tuesday
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