Overview

The fundamental theme of work in the Knowles lab is the application of genetics to improve human health. We view this as a continuum from Discovery, to the development of Model Systems, to Clinical Translation and larger Public Health efforts.

Currently, discovery and basic translational efforts center on understanding the genetic basis of Insulin Resistance (IR) and related cardiovascular traits. We are using Genome Wide Association Studies (GWAS) coupled with experimentation in model systems both in vitro and in vivo, ranging from classic cell lines to induced pluripotent stem cells (iPSCs) to mouse models. 

Clinical-translational research efforts in the lab are at the intersection of genetics, insulin resistance, and hypercholesterolemia. We are asking things like if we can improve an individual’s risk of developing disease by giving them information about their inherited risk of heart disease (i.e. their genetic risk score). We are also performing a clinical trial to determine the mechanism of statin-associated diabetes, which predominantly occurs in those with insulin resistance. 

Finally, we are attempting to raise the profile of Familial Hypercholesterolemia (FH), an inherited disease that causes extremely elevated LDL cholesterol levels and risk of coronary disease. It is a major focus of ours given its morbidity and mortality and public health impact. As the Chief Research Advisor for The FH Foundation (FHF) – a patient-led non-profit research and advocacy organization – we helped lead efforts in establishing a national patient registry for FH (CASCADE FH), applying for an ICD10 code for FH, advocating for genetic testing to be offered to FH patients, and are now using cutting-edge “big-data” approaches to identify previously undiagnosed FH patients in electronic medical records (FIND FH). We collaborate with the CDC, AHA, and ACC on these efforts.

Our lab has published over 100 papers with research projects currently funded by the NIH, AHA, ADA and the Doris Duke Charitable Foundation.

Relevant links

Stanford Center for Inherited Cardiovascular Disease (SCICD)