Amit Lahiri, Ph. D.
Sr.Scientist,Pharmacology
Mitochondrial function in regulating immune response
Lab Webpage
https://sites.google.com/view/csir-cdri-pcn201/home
1. Role of gut bacteria in liver disease:
Nonalcoholic steatohepatitis (NASH) is characterized by an enhanced Reactive oxygen (ROS) production, lipotoxicity and pro-inflammatory cytokine production in the liver cells-comprising of hepatocytes, kupffer cells (KC), stellate cells, NK cells. This transition from simple steatosis to NASH is incompletely understood, however it requires ‘multiple parallel hits’ where already fat engorged hepatocytes are triggered by pathogenic gut components. Liver gets the blood supply mainly from portal vein which is rich in pathogen derived molecules like Toll like receptor (TLR) ligands. Damage, dysfunction of the gut epithelium or intestinal dysbiosis (change in gut microbiome) can activate liver immune response as TLRs are expressed in hepatocytes, kupffer cell and dendritic cells. We will identify the molecular mechanisms of how gut bacteria regulates liver disease progression.
2. Mitochondrial function in regulating immune response:
New research has challenged the traditional view of mitochondria as a mere bioenergetic organelle, further elucidating its role in signaling that contributes to cell death, proliferation and differentiation. In addition to various human diseases (e.g. Leigh syndrome) arising due to direct mutations in the mitochondrial DNA, mitochondria has also been associated with cardiovascular disease, Inflammatory Bowel Disease (IBD) and diabetes. During ATP production, as a by-product of oxidative phosphorylation, reactive oxygen species are generated in the mitochondria. Various stress processes like increased metabolic rates, DNA release, hypoxia and membrane damage or mitophagy (autophagy of mitochondria) leads to an enhanced mitochondrial ROS generation which has potential impact on the cellular immune response. We plan to understand the role of mitochondrial dynamics in modulating the immune function/cell migration in arthritis, IBD and NASH.