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Jeffrey Bender, MD

Robert I. Levy Professor of Medicine (Cardiovascular Medicine) and Professor of Immunobiology
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Additional Titles

Associate Chief, Cardiovascular Medicine, Internal Medicine

Senior Vice Chief for Academic Development, Cardiovascular Medicine

About

Titles

Robert I. Levy Professor of Medicine (Cardiovascular Medicine) and Professor of Immunobiology

Associate Chief, Cardiovascular Medicine, Internal Medicine; Senior Vice Chief for Academic Development, Cardiovascular Medicine

Appointments

Education & Training

Research Fellow
Stanford University (1988)
Fellow
Stanford University (1986)
Resident
Yale-New Haven Hospital (1982)
MD
University of California/San Francisco (1979)

Research

Overview

My laboratory has had a longstanding interest in inflammation and immunity, as they relate to vascular physiology and pathology. The interactions between mononuclear leukocytes and endothelial cells play major roles in atherogenesis, acute and chronic manifestations of atherosclerosis, angiogenesis and allograft rejection. We have extended these studies to evaluating effects of ovarian steroid hormones on endothelial function. The work is performed at the cellular, molecular, and pre-clinical animal model levels. Our major efforts are directed at:

(1) Integrin-dependent leukocyte adhesion and T cell/macrophage gene expression.

We have discovered that when β2 integrins are engaged in T lymphocytes, labile mRNAs that are normally rapidly degraded are markedly stabilized. This includes transcripts encoding many immune and pro-inflammatory cytokines, such as TNF, IFN-γ, IL-1, and IL-17. We have defined the signal transduction cascade, which involves Rho family GTPases, and modulation of select RNA-binding proteins, most notably HuR. Through proteomics approaches, we have recently defined integrin-induced nuclear protein-protein interactions, which we believe will be important targets for molecular therapeutics. In addition to our studies on cells of the adaptive immune system, we have recently extended our work to innate immune cells, namely monocyte/macrophages. Many of the aforementioned signaling events occur in these cells as well. Relevant integrin-stabilized mRNAs in macrophages include those encoding angiogenic molecules, such as VEGF, MMPs and angiopoietins, and many of the pro-inflammatory molecules mentioned above. To determine the role of this adhesion-induced mRNA stabilization mechanism in vivo, we have recently targeted the HuR gene, and are using tissue-specific knockout mice for pre-clinical studies.

Macrophage-specific HuR knockouts indeed have prominent angiogenic defects in response to inflammation or ischemia. Vascular remodeling, atherosclerosis and allograft rejection models are being developed with these genetically modified animals.

(2) Influence of ovarian steroid hormones on endothelial activation and endothelial progenitor cell function.

The effects of estrogen on the endothelium remains a major question, despite clinical controversies regarding hormone replacement therapy in postmenopausal women, We have defined a splice form of estrogen receptor (ER)α, ER46, that is plasma membrane-targeted in endothelial cells and which initiates rapid signaling responses, leading to eNOS activation, nitric oxide release and vasodilation in vivo. Most recently, we have used a variety of cell imaging techniques, including FRET and TIRF microscopy, to demonstrate that ER46 has transmembrane spanning and ectodomains, and multiple membrane pools. This has never been described for a steroid hormone receptor, and provides a tremendous opportunity for differential therapeutic targeting.

(3) Effects of metabolic syndrome-associated lipids on endothelial function.

We have recently defined a series of endothelial cell signaling defects imparted by free fatty acids, leading to a state of "VEGF resistance", and greatly impaired responses to angiogenic growth factors. We have documented a mechanistic role of ceramide generation, in vitro, and demonstrated that such lipids cause impaired angiogenic responses to hindlimb ischemia in murine models. Current studies include mapping the cellular and molecular defects, those which occur both at the plasma membrane and Golgi.

Medical Subject Headings (MeSH)

Cardiology; Endothelium; Immune System; Inflammation; Macrophages; RNA Stability; T-Lymphocytes

Research at a Glance

Yale Co-Authors

Frequent collaborators of Jeffrey Bender's published research.

Publications

2023

2022

2019

2018

2016

Academic Achievements & Community Involvement

  • activity

    Cardiovascular Research

  • honor

    Young Investigator Award

  • honor

    Sackler Foundation Award

  • honor

    Andrew P. Mellon Award

  • honor

    Clinical Investigator Award

Clinical Care

Overview

Jeffrey Bender, MD, is a cardiologist and immunobiologist who cares for patients with a wide range of cardiovascular (CV) issues and disorders, ranging from CV prevention to angina, heart failure, and atrial fibrillation. He is committed to vascular research, which will ultimately lead to better care for heart patients.

Dr. Bender says he chose cardiology partly because he wanted to be able to provide both acute and critical care, as well as long-term preventive care. He has found working with heart patients rewarding, especially when he is able to use the latest advances to help them.

In addition to caring for patients, Dr. Bender is the Robert I. Levy Professor of Preventive Cardiology and a professor of immunobiology at the Yale School of Medicine. He is also the senior vice chief for academic development in the cardiovascular medicine division. His own research interests are in women’s vascular health, inflammation, angiogenesis, vascular injury, and transplantation.

Clinical Specialties

Internal Medicine; Cardiovascular Medicine

Fact Sheets

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

Yale Medicine News

Get In Touch

Contacts

Academic Office Number
Appointment Number
Clinic Fax Number
Mailing Address

Cardiovascular Medicine

PO Box 208056, 333 Cedar Street

New Haven, CT 06520-8056

United States

Locations

  • 300 George Street

    Academic Office

    Ste Cardiovascular Research Center, 773G

    New Haven, CT 06511

  • Patient Care Locations

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