We study fundamental aspects of how the immune system is influenced by and influences metabolism. We tend to think of it as systemic and cellular immunometabolism. While the projects introduced below may seem segregated, there is common overlap and broad applicability to a number of disease conditions such as diabetes, obesity, heart disease and infection.
Mapping the physiological importance of energy/nutrient sensing pathways
Energy and nutrient sensing are core regulators of metabolism and the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) coordinate a vast number of these outputs. We are trying to understand key signaling nodes of these important regulators by using targeted knock-in mouse models. We are interested in how these pathways affect obesity, atherosclerosis, metabolic-associated fatty liver disease and inflammation.
Linking choline metabolism and immunity
Choline is an essential nutrient and has three important fates. It is a precursor for the main phospholipid PC, can be made into acetylcholine or can feed into the one carbon cycle. We have been focused on choline metabolism in immune cells. We are asking what is the importance of choline uptake and downstream metabolism for immune cell function and also how inflammatory signals alter choline metabolism.
Mapping immunometabolism in fatty liver disease
Immune cells are everywhere and play important roles under normal and disease conditions. We know that the metabolism of immune cells can drive their function, but we do not know the metabolic state of these cells as diseases progress. Here we are using flow cytometry to measure metabolic programs in preclinical (mouse) and clinical liver isolates to understand how metabolism might be driving inflammation of various immune subsets and cell types
Cell death pathways in diabetes
How cells die is extremely important and in most cases, is a regulated and programmed process. There are key molecular regulators of these various cell death pathways. While much is known about how they are altered during disease or how they contribute to disease progression, there is still much to learn. In a collaborative project with Dr. Subash Sad, Dr. Erin Mulvihill and Dr. Jenny Bruin, we've embarked on a journey that has lead us to the pancreas...