Kathryn J. Moore, PhD, the Jean and David Blechman Professor of Cardiology in the Department of Medicine at NYU Grossman School of Medicine, has been awarded the Lefoulon-Delalande Institut de France Grand Prize in Science (the Grand Prix scientifique) for 2024.

Dr. Moore, also director of the Cardiovascular Research Center at NYU Langone Health, was honored for her answers to central questions in the field of cardiovascular physiology, including how persistent activation of the immune system (chronic inflammation) by excess cholesterol drives the development of plaques in the arteries of patients with atherosclerosis.

The award is conferred annually by the Lefoulon-Delalande Foundation at the Institut de France in various areas of medical science. With a different theme each year, although often focused on cardiology, the prize comes with an award of €600,000 (roughly $650,000), making it the largest in this area of research.

Dr. Moore’s research team discovered that the immune system recognizes certain (oxidized) forms of cholesterol using signaling proteins (receptors) designed to detect foreign invaders, such as bacteria. This immune response sets off chronic inflammation of the arteries, which results in the formation of plaques, compromising arterial blood flow and potentially leading to heart attacks.

Dr. Moore and colleagues also showed that when immune system cells known as macrophages engulf oxidized cholesterol, it can lead to the formation of cholesterol crystals that sound an inflammatory alarm. These intracellular cholesterol crystals trigger a protein group called the NLRP3-inflammasome complex. This complex is responsible for generating the potent pro-inflammatory cytokine interleukin-1b, whose inhibition has been shown in clinical trials to reduce risk of cardiovascular events.

“I am thrilled to receive this prize that honors the work carried out by my research team over the last two decades,” said Dr. Moore. “It has been an honor to work with such talented trainees and world-class colleagues in pursuit of answers to why chronic inflammation develops in response to hyper-cholesterolemia and drives cardiovascular diseases that place such a burden on millions of patients globally.”

In other work, Dr. Moore and colleagues revealed the role of a molecule called netrin-1 in causing macrophages to accumulate in atherosclerotic plaques and fat (adipose) tissue of obese individuals to drive a vicious circle of chronic inflammation, insulin resistance, and cardiometabolic disease. Dr. Moore also made discoveries on the role of tiny RNA molecules in regulating the pathways that control cholesterol levels in cells and the blood.

She showed that these “microRNAs” can repress the pathways that help cells rid themselves of excess cholesterol, resulting in the accumulation of cholesterol-laden immune cells in plaques and the development of atherosclerotic disease. Importantly, she found that microRNAs, in particular miR-33, could be targeted therapeutically to promote the normal balance of cholesterol in the body.

“The impact of Dr. Moore’s work on both the current and near-future of treatment for cardiovascular diseases is nothing short of profound,” said Glenn I. Fishman, MD, director of the Leon H. Charney Division of Cardiology at NYU Grossman School of Medicine. “It is great to see such an innovative and dedicated scientist be recognized in this way,” added Dr. Fishman, who is also vice chair for research for the Department of Medicine.

“There is no better example than Dr. Moore of the kind of exemplary scientist we seek to support at our institution,” said Dafna Bar-Sagi, PhD, senior vice president, vice dean for science, and chief scientific officer at NYU Langone. “Congratulations to her and the entire cardiology team.” 

Dr. Moore shares the award this year with Christopher Glass, MD, PhD, professor of Cellular and Molecular Medicine at the University of California, San Diego. Previous awards recognizing Dr. Moore’s research include, in 2022, a Gill Heart and Vascular Institute Award, which honors individuals who have made outstanding contributions to the field of cardiovascular medicine. In 2021, she was elected to the National Academy of Sciences, among the highest honors in the scientific field. Members of the academy serve pro bono as “advisers to the nation” on science, engineering, and medicine.

Last, in 2017, Dr. Moore received a $6.7 million Outstanding Investigator Award from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. The award funded her work seeking to determine the role of an unusual form of genetic material called long noncoding RNA, or lncRNA. She found that this class of molecules regulates the body’s immune response to plaques, which are made of cholesterol, fatty substances, and cellular waste that blocks arteries. Understanding IncRNAs may lead to new treatment approaches for cardiovascular diseases that remain the leading cause of death worldwide, she says.

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