About the Lab
Our research is focused on the regulation of lipid and lipoprotein metabolism. Circulating lipoproteins perform the essential function of moving cholesterol, triglycerides, and other hydrophobic lipids between tissues to meet varying metabolic needs. It is well known that high levels of LDL cholesterol (the “bad cholesterol”) and triglycerides are associated with increased risk of heart disease. Conversely, high levels of HDL cholesterol (the “good cholesterol”) are inversely correlated with risk. Although LDL lowering therapies have had a significant effect on reducing risk of death from heart attack and stroke, there is a tremendous need for new therapeutic strategies for further risk reduction.
Lipid and energy metabolism are closely connected, and share a complex regulatory network involving the interplay of multiple organ systems. With the growing epidemic of obesity, there has never been a greater need to understand how one’s genes help determine an individual’s susceptibility to these complex diseases. Recent studies have provided a wealth of data about genetic variants that are associated with lipid levels, and the corresponding risk of obesity, diabetes, and cardiovascular diseases in humans. The next step forward involves “reverse translation” into model organisms to clearly identify the causal genes and pathways responsible. We use a combination of viral gene delivery and classical gene targeting strategies to investigate gene function in model organisms. These physiological studies are complemented by cell based and in vitro approaches to elucidate molecular mechanisms.
Key Areas of Interest
- Arv1, an ER-Golgi lipid transporter and its role in mammalian energy homeostasis
- Factors influencing de novo cholesterol synthesis and their role in cardiometabolic disease
- Methods for somatic overexpression, knockdown and editing with viral vectors
- Novel gene therapy vectors for the treatment of rare lipid disorders
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