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Gastroenterology

Nighot Lab

Dr. Prashant Nighot’s research focuses on intestinal mucosal homeostasis in health and disease. The lab is interested especially in the role of defective intestinal tight junction (TJ) barrier in inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. TJ barrier defects allow penetration of luminal antigens, leading to excessive immune and inflammatory response.

Kushal Saha, Dr. Prashant Nighot, Dr. Ashwinkumar Subramenium Ganapathy and former lab team member Eric Suchanec in a lab

Lab Details

Recent work has focused on the role of autophagy in TJ barrier regulation. Autophagy, which also means self-eating, is a cell survival mechanism that degrades unnecessary, misfolded and long-lived proteins and organelles and helps cell survive under stress. The lab’s pioneering studies have shown that autophagy enhances TJ barrier via the degradation of pore-forming TJ protein claudin-2.

Dr. Nighot’s lab is also interested in investigating targets to combat IBD using novel intracellular pathways as well as the role of matrix metalloproteinases in intestinal inflammation.

The lab employs in-vivo approaches including several novel mouse models of intestinal inflammation, in-vitro cellular and molecular methods, and advanced imaging techniques to examine their hypotheses.

Meet the Team

Profile Photo: Prashant Nighot
Prashant Nighot, MVSc, PhD

Associate Professor and Vice Chair for Research, Medicine

Research Topics and Current Projects

Role of autophagy in TJ barrier regulation

The lab is currently conducting an NIH-funded study investigating the molecular mechanisms of autophagy regulation of TJ barrier and if autophagy-mediated enhancement of TJ barrier can prevent intestinal inflammation.

Investigating targets to combat IBD

One of the lab’s ongoing projects studies the role of the aryl hydrocarbon (AhR) pathway in TJ regulation. In a collaborative study, the laboratory is using a novel, non-toxic ligand to activate the AhR pathway to attenuate intestinal inflammation via the enhancement of TJ barrier.

Role of matrix metalloproteinases in intestinal inflammation

On another project, the lab is investigating the role of matrix metalloproteinases (MMPs) in intestinal inflammation. MMPs play a role in the organization of extracellular matrix and wound repair, but their aberrant expression during inflammation can affect mucosal architecture. Macrophages secrete MMP-12 when activated during the inflammation. The lab has recently demonstrated how MMP-12 enables macrophages to transmigrate through colonic mucosa during colitis and how this process affects colonic TJ barrier and mucosal integrity.

Kushal Saha, a graduate student in Dr. Prashant Nighot’s lab, works on Ussing Chambers in the lab.

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