Our lab’s interest lies primarily in the area of inflammation with specific interests on the role of adenosine triphosphate (ATP) in its modulation. We have proposed the “two-hit hypothesis for inflammation“ wherein a variety of insults such as bacterial infections, protein aggregations in neurodegenerative diseases, or cellular injury/ischemia serve as the first hit leading to the activation of innate immune cells such as macrophages or microglia leading to the production of prostaglandin E2 from the enzyme cyclooxygenase 2 (COX-2). However, the first hit also mediates cell death in the vicinity leading to the release of contents of the dying cell into the extracellular milieu, of which ATP is prominent. This extracellular ATP (eATP), through purinergic (P2) receptors, serves as the second hit, leading to further increase in the levels of COX-2, transcriptionally as well as through post-transcriptional mechanisms, leading to enhancement of inflammation (Fiebich et al., 2014, Frontiers in Cellular Neuroscience 8:260). Sustained activation of the P2 receptors also interferes with the resolution of inflammation and contributes to the chronicity of inflammation. Our lab has identified the P2 receptor-COX-2 axis in the enhancement of systemic inflammation (Akter et al., 2021, Journal of Leukocyte Biology 110:663) and also identified its role in imparting migration/invasion properties to various cancer cells (Sharma et al., 2021, Frontiers in Pharmacology 11:617211).
Overall, our lab is working on these broad areas of study:
We had several talented students joining the lab for their M.Sc. dissertation work who then went for Ph.D. to prestigious places throughout the world such as All India Institute of Medical Sciences-New Delhi (Pawan Tiwari), Jawaharlal Nehru University (Anjali Chauhan, Ayushi Chhabra), International Centre for Genetic Engineering and Biotechnology-New Delhi (Yadya Chawla), Indian Institute of Science (Ashika Dhimal, Niranjan Kumar), Institute of Liver and Biliary Sciences (Nidhi Nautiyal, Pinky Juneja), Indian Institutes of Science, Education and Research-Pune (Shivang Goswami), National Centre for Biological Sciences (Aniket Kashyap, Aparna Upadrasta), National Institute of Immunology (Gagan Dev), Ohio State University (Anuvrat Sircar), Rosalind Franklin University-Chicago (Babita Thadari), University of Bonn (Pallavi Pant), University of Colorado (Prakriti Kandel), University of Nebraska (Ashish Das), and University of Otago (Simran Lakhina).
