Penn scientist receives distinguished investigator award for patient-oriented research

PHILADELPHIA– The Association for Clinical and Translational Science (ACTS), a non-profit membership association of translational scientists from the nation's leading academic medical centers, has awarded the Edward H. Ahrens Jr. Distinguished Investigator Award for Patient-Oriented Research Translation to Daniel J. Rader, MD, chair of the department of Genetics in the Perelman School of Medicine at the University of Pennsylvania.

Rader is a physician-scientist who has made numerous contributions to the prevention of heart disease. The award is presented nationally to a "senior investigator whose innovative research or education leadership has had a major impact on or through clinical and translational science, specifically in bench-to-bedside translational research."

He is a globally renowned expert in the genetics and physiology of lipoprotein metabolism and atherosclerosis, the hardening and narrowing of the arteries due to fatty buildup. Lipoproteins transport fats such as cholesterol and triglycerides throughout the body. Atherosclerosis is the primary origin of cardiovascular disease, and in turn, the leading cause of death for both men and women in industrialized nations, including the United States. About 630,000 Americans die from heart disease each year–one in every four deaths. Physiological risk factors for atherosclerosis include high levels of low-density lipoprotein cholesterol (LDL– "bad cholesterol") in the blood and low levels of high-density lipoprotein cholesterol (HDL–"good cholesterol").

Rader's research efforts include identifying new genes and pathways involved in regulating lipoprotein metabolism and defining its role in atherosclerosis. This approach, known as "functional genomics," can locate potential new targets for medications and gene-editing techniques for addressing serious heart-related conditions. For example, Rader and colleagues identified the SORT1 gene as a key novel regulator of LDL levels and risk of coronary disease. Rader and colleagues also found that ADAMTS7, a gene implicated in arthritis, was also associated with the risk of developing coronary artery disease and that deleting the gene in mice protected them from atherosclerosis.

Rader is a world expert in the biology of HDL metabolism. His lab showed that the ability of HDL to extract cholesterol from cells is a better predictor of coronary disease compared to its simple level in the blood–significantly refining the established fact that high HDL levels are associated with a lower risk of heart disease. Specifically, while high HDL levels may indicate an efficient purging of excess fats, in some cases they may reflect the liver's inability to push out cholesterol for excretion from the body, leading to a build-up in the blood.

He has also made translational discoveries related to triglycerides, another fatty substance in the blood that deposits in arteries. Rader and colleagues demonstrated that an antibody that blocks a protein called APOC3 can reduce triglycerides in mice, paving the way for development of a new therapeutic approach. Rader and colleagues also found that blocking the activity of a protein called ANGPTL3 with an investigative injectable antibody reduced triglycerides. This is crucial research because while statins are widely used to lower LDL cholesterol, there are fewer options for lowering triglycerides.

In addition to helping address common conditions that affect millions of people, Rader also tackles rare diseases. He and colleagues helped identify the molecular defect in a rare genetic disorder that causes extremely low levels of low-density lipoproteins, resulting in plaque that can clog arteries. This discovery led to the development of inhibitors of this pathway, which reduced levels of LDL cholesterol. Rader then spent over 10 years converting one such potential inhibitor, which had been abandoned by its pharmaceutical developer, into a treatment for homozygous familial hypercholesterolemia (HoFH), a rare condition characterized by extremely high levels of LDL, leading to heart disease in children. This resulted in FDA and European approval of lomitapide, the first effective medication for treating HoFH.

Rader's awards include the Burroughs Wellcome Fund Clinical Scientist Award, Bristol Myers Squibb Cardiovascular Research Award, Doris Duke Charitable Foundation Distinguished Clinical Investigator Award, AHA Jeffrey M. Hoeg Award for Basic Science & Clinical Research, AHA Clinical Research Prize, the CRF Distinguished Clinical Research Award, and the ACP Science Award. He is an elected member of the American Society for Clinical Investigation, the Association of American Physicians, and the National Academy of Medicine.

At the Perelman School of Medicine, he has received the William Osler Patient Oriented Research Award, Donald B. Martin Outstanding Teacher Award, and the Outstanding Faculty Award from the Department of Medicine.

Rader earned his medical degree at the Medical College of Pennsylvania, followed by an internship and residency at Yale-New Haven Hospital and a post-doctoral fellowship at the National Institutes of Health.

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Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.

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