Sinju Sundaresan, Ph.D.

1. Gut-brain axis in regulation of metabolism

"We are what we eat" couldn't be truer these days, given the obesity epidemic and its associated comorbidities including type 2 diabetes. Chronic high fat feeding alters fat sensing by the gut endocrine cells that prime the body towards increased food intake and higher thresholds for satiety following a meal. The goal of this project is to investigate mechanisms underlying altered fat sensing by enteroendocrine cells (EECs), identify downstream signaling targets, and determine changes in expression and localization of fatty acid (FA) receptors on EECs. Nutrient induced signals arising from EECs in the gut are transmitted to the brain for regulation of food intake and hunger/satiety sensations. This occurs via gastrointestinal vagal afferent neurons. EECs are innervated by and/or lie in close proximity to the vagus nerve that relays luminal nutrient status to the brain, based on input from chemical and hormonal messengers, or distension of the gut wall. Cell bodies of vagal afferent neurons from all organs including the GI tract are housed in the nodose ganglion. This project will also investigate whether chronic fat exposure alters expression of FA-responsive receptors in the nodose ganglion and determine its impact on neuronal membrane excitability. The two-fold approach will help strengthen our understanding of how nutrient-induced signals along the gut-to-brain axis is impacted by obesity.


2. Aging induced changes in the intestinal stem cell niche

Aging is a complex process characterized by decline in biological and cognitive function. Gastrointestinal alterations and associated pathophysiology underlie several complications including increased susceptibility to infection, delayed wound healing, altered motility, malabsorption, and cancer. The intestinal epithelium turns over every 3-5 days; homeostasis is maintained by a balance between differentiation to epithelial cell types and renewal of the intestinal stem cell (ISC) niche. With aging, an increased propensity to differentiation and commitment at the cost of ISC renewal has been reported. This project will investigate mechanisms underlying slow ISC renewal using fluorescently labeled mice reporter lines.