The overall theme of Dr. Knowles's work is to understand the genetic basis of complex cardiovascular diseases such as coronary disease and insulin resistance. Currently, he is involved in genome wide association (GWA) studies of coronary disease through the NIH-funded ADVANCE study and of insulin resistance through the international GENESIS project. After using the GWA approach to discover and validate interesting candidate genes, Dr. Knowles hopes to explore the biology underlying these genes and pathways using cell culture and in vivo model systems. He is also using iPSC technology (induced pluripotent stem cells) to develop model systems for the study of insulin resistance through the NIH-funded GENESiPS project.

Dr. Knowles also has a strong interest in developing tools to help translate newly emerging genetic data into clinical practice and is currently the PI of a randomized trial examining whether it is possible to improve patient coronary disease risk factor profiles by giving them information about their inherited risk of coronary disease.

Clinically, Dr. Knowles is interested in the care of patients with inherited cardiovascular conditions. In particular he is focused on individuals with Familial Hypercholesterolemia. He also has an interest in treating Hypertrophic Cardiomyopathy. He takes care of these patients in the Stanford Center for Inherited Cardiovascular Disease.