Mary Sheppard, MD

The Sheppard laboratory prioritizes research that can improve quality of life for people with Marfan syndrome and related disorders. We focus on therapeutics that have a high likelihood of successfully translating into direct human care, with an emphasis on timely implementation. The largest proportion of work addresses aortic disease, as this is a leading cause of morbidity and mortality in people with Marfan syndrome and related disorders. However, we do not overlook the multisystemic forms of suffering that can also be caused by genetic variants.

Over the last decade, we have been evaluating the impacts of the renin-angiotensin system on Marfan aortopathy. This includes the role of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and oligonucleotides targeting angiotensinogen.

We also investigate whether and how medications commonly used to lower cholesterol help the aorta. Studies in mice have suggested that pravastatin and atorvastatin may have beneficial effects on the aorta in Marfan syndrome. My laboratory has been conducting NIH-funded research to better understand the translatability of these findings to human care. We are evaluating how these findings relate to overall metabolic health in people with Marfan syndrome.

We are pursuing research studies that enable patients with aortic disease to be more active. The Marfan Foundation funded our team to study how musculoskeletal biomechanics contributes to early-onset hip osteoarthritis in Marfan syndrome. We hope to discover specific exercises that prevent development of hip pain in people as they age.