The Ashley lab is focused on understanding the integrative function of the heart: how changes in DNA, gene expression and protein signaling interact and integrate to define cellular function; how cardiac myocytes interact with each other and how they respond to molecular and biophysical stimuli; how four chambers, four valves, ten leaflets and five papillary muscles coordinate their contraction and relaxation to supply just enough output for the tissues. The heart serves every organ in the body and when it fails, every organ can fail too. We are focused on how to stop the heart failing.

So we are systems biologists. We study networks: co-expression networks of gene expression and pathways assembled via text mining of the published literature. We test questions which can be answered entirely in silico but we also use the wet lab to explore the biology of key  genes and signaling modules. We use cell systems for upregulating or silencing genes. We have transgenic models and microsurgical models of disease. We are one of the few labs to place stents in mice. With collaborators, we can test beat rate and conduction velocity in cultured myocardial cells. We are also very interested in integrative function at an organ level, investigating basic mechanisms of cardiac contraction and relaxation via pressure-volume loops in large animal models and in patients.

A major part of our effort is focused on the apelin-APJ signaling system. We were among the first to describe the significance of this system for cardiovascular disease. In close collaboration with the laboratory of Thomas Quertermous, we investigate the fundamental biology of apelin-APJ. We have contributed data on in vivo biology and have transgenic models which we hope will allow us to describe the true pathophysiological role for the system. We are actively moving these insights from the bench to the clinic.

We are very interested in human genetic variation. We run the Stanford Cardiovascular Institute tissue bank and use collected samples to study pharmacogenomics in heart failure. We are interested in novel approaches to combining genomic and genetic data. In addition to common variation, we are interested in private mutations that cause cardiomyopathy and arrhythmia syndromes within families. This interest leads all the way to the clinic where we run the Stanford Hypertrophic Cardiomyopathy Center. This disease is the number one cause of sudden death in young people and this leads to an intensive interest in the hearts of athletes. We run the Stanford Hospital Cardiopulmonary Exercise lab and collaborate with the Stanford Human Performance Laboratory including the laboratory of Victor Froelicher and Jonathan Myers. We help with the preparticipation screening of the Stanford athletes and the San Francisco 49ers football team.

Check out our center on the web: www.hcm.stanfordhospital.com

Recent publications from the Ashley Lab

Ashley Lab in the news

View our current Cardiomyopathy Seminar Series, held each Tuesday at noon