My research focuses on the use of optical spectroscopy and imaging to understand and diagnose disease. In particular, I am interested in how macrophages catabolize objects that cannot be internalized by standard phagocytic mechanisms and how this novel method of degradation effects the biology of conditions such as atherosclerosis and white adipose tissue inflammation. Data from myself and others have defined a process, termed exophagy, in which large moieties or species tightly bound to the extracellular matrix are initially digested in an extracellular, acidic, lytic compartment. A similar but distinct mechanism is used by osteoclasts, tissue-specific macrophage-like cells that create an extracellular, acidic, lytic compartment to degrade bone. We have studied exophagy in the context of macrophage degradation of aggregated low density lipoproteins resulting in foam cell formation, as occurs during atherogenesis. A detailed understanding of these processes is essential for developing new strategies to prevent atherosclerosis.
Recently, we extended our studies of exophagy to crown-like structure macrophages found in inflamed white adipose tissue. White adipose tissue inflammation has been linked to the pathogenesis of obesity-related diseases including type 2 diabetes, cardiovascular disease and cancer. Understanding this novel process for degradation of dead adipocytes provides insights into adipose tissue remodeling and may suggest new approaches to modulate adipose inflammation and the diseases it causes. Further, we investigate the use of spectroscopic techniques for the non-invasive diagnosis of white adipose tissue inflammation, as well as other diseases. A non-invasive detection modality for adipose inflammation would define those individuals likely to benefit from interventions and could also be used to monitor efficacy of therapy. Taken together, our work strives to understand basic macrophage biology that contributes to disease, develop therapies based on this biology, and identify and monitor individuals harboring disease.