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William Sessa, PhD

Alfred Gilman Professor Emeritus of Pharmacology
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Alfred Gilman Professor Emeritus of Pharmacology

Biography

Dr. William C. Sessa is the Alfred Gilman Professor and Vice Chairman in the Department of Pharmacology and Director of the Vascular Biology & Therapeutics Program at Yale School of Medicine. His work defined the molecular aspects and physiological implications of endothelial nitric oxide synthase (eNOS) activation and has contributed towards the elucidation of how nitric oxide (NO) regulates angiogenesis, vascular permeability, atherosclerosis and vascular remodeling. He cloned eNOS as a post-doc and subsequently identified eNOS subcellular trafficking, post-translational lipidation, phosphorylation and regulated protein-protein interactions as mechanisms to regulate NO production and cardiovascular homeostasis. In addition to work on eNOS, he has made several additional important contributions emanating from his work on eNOS including elucidating the role of caveolae microdomains of the plasma membrane in signaling, defining the role of Akt as an important kinase regulating the morphogenic and survival pathway for angiogenic growth factors, and the identification of the enzyme required for dolichol synthesis in mammalian cells. This latter pathway is an evolutionarily conserved pathway for all protein N-glycosylation reactions in the endoplasmic reticulum and loss of functions mutations arising in this enzyme can cause a congenital disorder of glycosylation, pediatric epilepsy and movement disorders. He has trained many graduate students, mentored several clinical scientists and over 40 post-doctoral fellows, most of which are in leadership positions in academia.

Appointments

Education & Training

Post-doctoral fellow
Pharmacology, The University of Virginia Health Sciences Center (1993)
Post-doctoral fellow/Senior Scientist
The William Harvey Research Institute (1991)
PhD
New York Medical College (1989)

Research

Overview

The vascular endothelium is the largest endocrine organ in the body, at the interface of blood and tissue. As such, many common diseases such as atherosclerosis, heart disease, cancer, macular degeneration and diabetes have a common signature of endothelial cell dysfunction. Our laboratory is focused on understanding the etiology of vascular dysfunction in these diseases and is focused on several broad aspects of endothelial cell biology and function.

We are exploring multiple avenues of research with a critical eye towards discovering new, biologically relevant therapeutic targets and pathways.

1. Elucidation how endothelial NOS (eNOS) is regulated in the context of normal physiology and in disease using cellular and molecular approaches in signal transduction. Particular areas are the study of cholesterol enriched plasmalemmal microdomains, caveolins, cavins, and downstream pathways.

2. Identification of new pathways that mediate the uptake and transcytosis of low density lipoprotein (LDL) and determining how LDL receptor influences vascular disease.

3. Proteomic analysis of protein phosphorylation using optogenetic approaches;

4 NgBR structure function and cellular biology in cholesterol metabolism and protein N-glycosylation;

We typically use basic molecular and cellular approaches and apply our findings to complex genetic systems (compound mutant mouse strains) to study blood vessel structure and function in physiology and disease.


Medical Subject Headings (MeSH)

Cardiovascular Diseases; Cell Membrane Permeability; Chemicals and Drugs; Circulatory and Respiratory Physiological Phenomena; Neoplasms

Research at a Glance

Yale Co-Authors

Frequent collaborators of William Sessa's published research.

Publications

2024

2023

Academic Achievements & Community Involvement

  • activity

    International Scientific Board

  • activity

    Cardiovascular Research

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