David Harris

Multiple randomized clinical trials have established that bariatric surgery (BS) is the most efficacious therapy for obesity and its associated metabolic diseases. It is increasingly clear that surgery leads to a complex host adaptation across multiple organ systems, the central and peripheral nervous system, the immune system, and the host microbiome. However, a mechanistic lynchpin has yet to be found and very little is known about how BS leads to simultaneous improvements across multiple organ systems. My research program is focused on the intersection of metabolic surgical operations, metabolism, and aging. I have a particular interest in how surgery effects organ-specific senescence, which in turn, effects organ function and systemic host metabolism and glucose regulation. Senescence is a cellular state of proliferative arrest induced within adipose tissue and other organs in response to stressors and aging. This is a self-propagating phenomenon associated with severe systemic metabolic diseases like diabetes, organ-specific dysfunction, and reduced survival. We have shown that sleeve gastrectomy (SG), now the most performed BS in the US, in mice leads to a weight-loss independent shift in host glucose metabolism and immunity, which protects animals from the development of metabolic disease – namely non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) – late in life. This is accompanied by an up-regulation in the cellular machinery capable of influencing senescence and senescence associated inflammation within adipose tissue. I plan to show that SG affects metabolic diseases like T2D and NAFLD, organ dysfunction, and healthy aging through modulation of senescence-associated pathways.

https://www.surgery.wisc.edu/staff/david-harris/