The Enteric Nervous System (ENS), often called the brain in the gut, is the second largest nervous system and it takes care of most of the digestive and much of the systemic functions in the body. However, despite its significant role, we have little clue on how it matures after birth to deal with our changing gustatory and maturing digestive roles, how it maintains in adulthood despite significant and continual stress from the movement of the gut to the presence of toxins in the lumen, and if, just like the central nervous system, it changes with age to become senile.

The Kulkarni lab works on understanding the developmental, cellular, and molecular biology that underlies these important post-natal biologies of the ENS. By using a combination of lineage fate-mapping models, protein and transcript-based molecular taxonomy of adult enteric neurons, and computational methods, we provided the first evidence of an adult ENS that is dynamic both at a cellular as well as at a developmental level. We were the first to show evidence of significant neuronal turnover in the adult gut, and also the first to show evidence of novel mesodermal derivation of a large proportion of neurons in the adult ENS. These neurons, by their expansion with age during the juvenile age and during aging, contribute both to the maturation and to the age-associated senility of the ENS. By identifying how these lineages respond to specific growth factors, we provide a possible way to rejuvenate and revitalize the aging senile ENS to cure gut dysfunction in the elderly.

We are interested in studying these developmental and cellular pathways, and how they are altered in response to diet, stress, sex, and intestinal microbiota, to better understand how diseases of the gut and of the gut-brain axis develop, and how regenerative and rejuvating therapies can be developed to prolong the healthspan.