Principal Investigator
Kodi Ravichandran
Research interests
Our laboratory works on how cells die and how these dying cells are cleared via efferocytosis. Specifically, we focus on:
- How dying cells communicate with other immune cells and tissue neighborhod via metabolites and other molecules
- What receptors and ligands are used in the interaction between dying cells and phagocytes
- The intracellular signaling within phagocytes that facilitate uptake and the responses of phagocytes post-engulfment
- Modifying the engulfment process for potential therapeutic benefits
Selected publications
- Medina CB, P Mehrotra, JSA Perry, SA Arandjelovic , Y Guo, S Morioka, B Barron, SF Walk, Ghesquire, A Krupnik, UM Lorenz, KS Ravichandran. Orchestrated release of metabolites from apoptotic cells function as novel tissue messengers. 2020. Nature. 580:130-135. (as Article, with News and Views). (PMCID: PMC7217709).
- Details how metabolites released from apoptotic cells communicate with other cells and that pannexin channel opening during apoptosis is a key contributor to release of such metabolites
- Park D, AC Tosello-Trampont, MR Elliott, M Lu, LB Haney, Z Ma, AL Klibanov, KS Ravichandran. Brain-specific angiogenesis inhibitor 1 (BAI1) is a novel engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. 2007. Nature. 450:430-434.
- Identifies BAI1, an adhesion type GPCR as a receptor for phosphatidylserine, and that it can mediate signaling downstream via ELMO/Dock180/Rac pathway to faciliate engulfment of apoptotic cells
- Anderson CJ, CB Medina, B Barron, L Karvelyte, T Aaes, I Lambertz, JSA Perry, P Mehrotra, A Gonçalves, K Lemeire, G Blancke, V Andries, F Ghazavi, A Martens, G van Loo, L Vereecke, P Vandenabeele, KS Ravichandran. Microbes exploit death induced nutrient release by gut epithelial cells. 2021. Nature. 596:262-267.
- This work details how microbes can use the metabolites released from dying cells as a source of food/energy for their growth and infection within the gut, and defines some key pathways that the microbes use for this puprose.
- Maschalidi S, P Mehrotra, BN Keceli, HKL De Cleene, K Lecomte, R Van der Cruysen, P Janssen, J Pinney, G van Loo, D Elewaut, A Massie, E Hoste, KS Ravichandran. Targeting Slc7a11 improves efferocytosis by dendritic cells and wound healing in diabetes. 2022. Nature. 606(7915):776-784.
- This work identifies the soluter carrier protein Slc7a11 as a brake in efferocytosis by dendritic cells and that inhibition or loss of Slc7a11 can promote apoptotic cell clearance and thereby, promote wound healing.
- Morioka S, Kajioka D, Yamaoka Y, Ellison RM, Tufan T, Werkman IL, Tanaka S, Barron B, Ito ST, Kucenas S, Okusa MD, Ravichandran KS. 2022. Chimeric efferocytic receptors improve apoptotic cell clearance and alleviate inflammation. 185(26):4887-4903.
- This work describes the innovative design of a chimeric efferocytic receptor BELMO (combining PS recognition by phagocytes with intracellular signaling domains) that can effectively clear apoptotic cells in acute inflammation and thereby provide a benefit in multiple inflammatory insults.
