Jonathan C. Cohen
The University of Texas Southwestern Medical Center
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Primary Section: 42, Medical Physiology and Metabolism Secondary Section: 26, Genetics Membership Type:
Member
(elected 2022)
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Biosketch
Jonathan Cohen is a Professor of Human Nutrition at the University of Texas Southwestern Medical Center in Dallas (UTSW). After postdoctoral training with Scott Grundy and Helen Hobbs at UTSW, he was appointed as an assistant professor in the Center for Human Nutrition at UTSW (1994) and has remained there ever since. Together with his colleague Helen Hobbs, he has focused on the metabolism of two neutral lipids: cholesterol, which is the cardinal risk factor for coronary heart disease (CHD), and triglycerides, which have a causal role in the development of fatty liver disease. Their laboratory has identified genes responsible for two single gene disorders that cause very high levels of cholesterol (autosomal recessive hypercholesterolemia and sitosterolemia), and elucidated basic mechanisms in sterol uptake and excretion. They also showed that mutations that inactivate PCSK9 are associated with low levels of cholesterol in the circulation. People who carried these mutations enjoyed substantial protection from CHD and had no detectable adverse sequelae, even in homozygotes. FDA-approved agents targeting PCSK9 and ANGPTL3 are now available. Cohen has received the Passano Award in 2016 and the Ross award in 2023, both of which he shared with Hobbs.
Research Interests
Virtually all chemical reactions in living organisms take place in water. Early in vertebrate evolution, two molecules, cholesterol and triacylglycerols, became ubiquitous among vertebrate animals despite being completely insoluble in water. Both molecules are essential for life and both can be synthesized by all cells except red blood cells. Cholesterol, a neutral lipid that is highly soluble in phospholipid bilayers, stiffens and thickens cell membranes, rendering them less permeable to water and many small molecules. Triacylglycerols (also called triglycerides) are the primary vehicle for energy storage in most eukaryotes. The extreme hydrophobicity of these molecules has required the evolution of multiple complex pathways to synthesize, regulate, store, transport, and degrade them. Our laboratory focuses on identifying and elucidating the genetic and acquired factors that lead to accumulation of cholesterol in the circulation, the cardinal risk factor for coronary heart disease, and of triglycerides in the liver, the major cause of fatty liver disease.
