SUMMARY
Jordan D. Miller, Ph.D., is a cardiovascular disease researcher at Mayo Clinic. The overarching goal of Dr. Miller's research is to create innovative pharmacological and technological solutions that improve the quality and length of life for people with cardiovascular conditions and improve how Mayo Clinic delivers world-class care.
A main area of Dr. Miller's research focuses on mechanisms that contribute to age-related cardiovascular conditions. These mechanisms include cardiovascular calcification and stiffening; aortic valve narrowing and stenosis; vascular and endothelial dysfunction; and mitral valve prolapse and regurgitation. Dr. Miller also studies the effects of heart valve dysfunction on cardiac muscle.
Dr. Miller directs the Cardiovascular Disease and Aging Laboratory. In his lab, Dr. Miller uses insights from his mechanistic research studies to develop new pharmacotherapies aimed at slowing, halting and reversing disease progression. Notably, Dr. Miller's lab was the first to test the effectiveness of soluble guanylate cyclase activators in slowing progression of aortic valve calcification and stenosis. These activators are molecules that restore nitric oxide signaling, which is generally considered to be a protective signaling pathway in cardiovascular tissues. This work is moving toward large-scale clinical trials for final approval by the U.S. Food and Drug Administration (FDA). Research in his laboratory is supported by the National Institutes of Health and strategic industry partnerships.
Dr. Miller's role as co-vice chair of basic science research in the Department of Cardiovascular Surgery continues to inspire his secondary research focus — developing, testing and using innovative technology in cardiovascular surgery. These technologies include immersive virtual reality interventions to reduce patient stress before surgery and remote monitoring technologies to detect and predict clinical events after surgery.
Dr. Miller also collaborates with investigators in the Robert and Arlene Kogod Center on Aging. They study how cardiovascular conditions are affected by fundamental mechanisms of aging, also called cellular senescence.
Focus areas
Dr. Miller's research focuses mainly on developing new medicines to treat cardiovascular conditions for which surgery and palliative care are currently the only options.
- Mechanisms contributing to aortic valve calcification and stenosis. Aortic valve calcification is a progressive process that ultimately leads to aortic valve stenosis and the need for valve replacement through surgery. There are no available medicines that slow progression of aortic valve calcification or stenosis. Dr. Miller's laboratory has a longstanding interest in testing and developing medicines that prevent progression of valve calcification and that may delay or eliminate the need for valve replacement surgery. Two major biological areas of focus include strategies to restore nitric oxide signaling and methods to reduce accumulation or dysfunction of senescent cells.
- Identifying reciprocal regulators of skeletal and cardiovascular calcification. One of the major challenges in preventing cardiovascular calcification is preserving mechanisms that maintain bone ossification. Several of the mechanisms contributing to these processes overlap. Dr. Miller's lab conducts rigorous testing of therapeutic interventions on cardiovascular tissue and bone to ensure safety and effectiveness in aging populations.
- Understanding mechanisms contributing to vasomotor dysfunction in health and disease. Numerous harmful changes occur in blood vessels from high cholesterol, high blood pressure and aging. Cardiovascular disease stemming from the dysfunction or blockage of blood vessels is a leading cause of death. Some conditions, such as isolated systolic high blood pressure, don't have good treatment options. Dr. Miller's lab investigates mechanisms that contribute to vascular dysfunction in these different situations. Dr. Miller hopes to understand mechanisms that can be targeted with medicine to reduce illness and death from cardiovascular diseases.
- Understanding mechanisms contributing to mitral valve prolapse. There are no medical treatments to slow progression of mitral valve prolapse. Surgical repair or replacement of the valve is the only treatment option. Dr. Miller's laboratory is actively conducting high-throughput screening to identify novel mechanisms related to mitral valve prolapse, with a goal of identifying targets to slow disease progression.
A pivotal part of the success of Dr. Miller's work has been the multidisciplinary team he has assembled to approach this research. This team includes scientists, cardiologists, cardiac surgeons, radiologists and drug development experts.
Significance to patient care
The overarching goal of Dr. Miller's research is to develop novel medicines that slow or halt progression of cardiovascular diseases that currently lack viable treatment options other than surgery. Through the use of molecular screening on human tissue, novel strains of genetically modified mice, in vitro and cell culture methods, and novel drug development, Dr. Miller aims to provide truly novel and transformative treatment options for cardiovascular diseases and age-related conditions.
Professional highlights
- Heart Valve Society:
- Associate editor, Journal of the Heart Valve Society, 2024-present.
- Secretary/treasurer, board of directors, 2022-present.
- Member, board of directors, 2014-2022.
- Circulation Research:
- Reviewer, 2009-present.
- Editorial board member, 2012-2018.
- Ad hoc grant reviewer, AICS, CICS and Career Development Award study sections, National Institutes of Health, 2015-present.
- Ad hoc grant reviewer, Cardiovascular Biology Study Section-B, Veterans Affairs, 2015-present.