MEF2 and the Right Ventricle: From Development to Disease.

Loading...
Thumbnail Image

Date

2019-01

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

72
views
26
downloads

Citation Stats

Abstract

Pulmonary arterial hypertension is a progressive and ultimately life-limiting disease in which survival is closely linked to right ventricular function. The right ventricle remains relatively understudied, as it is known to have key developmental and structural differences from the left ventricle. Here, we will highlight what is known about the right ventricle in normal physiology and in the disease state of pulmonary arterial hypertension. Specifically, we will explore the role of the family of MEF2 (myocyte enhancer factor 2) transcription factors in right ventricular development, its response to increased afterload, and in the endothelial dysfunction that characterizes pulmonary arterial hypertension. Finally, we will turn to review potentially novel therapeutic strategies targeting these pathways.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.3389/fcvm.2019.00029

Publication Info

Clapham, Katharine R, Inderjit Singh, Isabella S Capuano, Sudarshan Rajagopal and Hyung J Chun (2019). MEF2 and the Right Ventricle: From Development to Disease. Frontiers in cardiovascular medicine, 6. p. 29. 10.3389/fcvm.2019.00029 Retrieved from https://hdl.handle.net/10161/20334.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Rajagopal

Sudarshan Rajagopal

Associate Professor of Medicine

I am a physician-scientist with a research focus on G protein-coupled receptor signaling in inflammation and vascular disease and a clinical focus on pulmonary vascular disease, as I serve as Co-Director of the Duke Pulmonary Vascular Disease Center. My research spans the spectrum from clinical research in pulmonary vascular disease, to translational research in cardiovascular disease, to the basic science of receptor signaling. 

Our basic science resesarch focuses on understanding and untapping the signaling potential of G protein-coupled receptors (GPCRs) to regulate inflammation in vascular disease. GPCRs are the most common transmembrane receptors in the human genome (over 800 members) and are some of the most successful targets for drug therapies. While it has been known for some time that these receptors signal through multiple downstream effectors (such as heterotrimeric G proteins and multifunctional beta arrestin adapter proteins), over the past decade it has been better appreciated that these receptors are capable of signaling with different efficacies to these effectors, a phenomenon referred to as “biased agonism”. Ligands can be biased, by activating different pathways from one another, and receptors can be biased, by signaling to a limited number of pathways that are normally available to them. Moreover, this phenomenon also appears to be common to other transmembrane and nuclear receptors. While a growing number of biased agonists acting at multiple receptors have been identified, there is still little known regarding the mechanisms underlying biased signaling and its physiologic impact.

Much of our research focuses on the chemokine system, which consists of approximately twenty receptors and fifty ligands that display considerable promiscuity with each other in the regulation of immune cell function in inflammatory diseases. Research from our group and others have shown that many of these ligands act as biased agonists when signaling through the same receptor. We use models of inflammation such as contact hypersensitivity and pulmonary arterial hypertension (PAH). PAH is a disease of the pulmonary arterioles that results in right heart failure and most of its treatments target signaling by GPCRs. We use multiple approaches to probe these signaling mechanisms, including in-house pharmacological assays, advanced phosphoproteomics and single cell RNA sequencing.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.