"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 to larger Public Health efforts.
Currently, discovery and basic translational efforts center on understanding the genetic basis of insulin resistance and related cardiovascular traits using GWAS studies coupled with exploration in model systems both in vitro (including classic cell lines as well as induced pluripotent stem cells) and in vivo (primarily mouse models). Clinical-translational research efforts in the lab are at the intersection of genetics, insulin resistance and hypercholesterolemia. We are asking if we can improve an individual’s risk by giving them information (i.e. genetic risk score) about their inherited risk of heart disease. We are also performing a clinical trial to determine the mechanism of statin-associated diabetes (which predominantly occurs in those with insulin resistance). Finally, Familial Hypercholesterolemia (FH) is a major focus 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 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. We helped lead the FHF efforts to establish a national patient registry (CASCADE FH), apply for an ICD10 code for FH, advocate 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."