Research Summary

Research in the Arandjelovic Lab is focused on the process of apoptotic (dying) cell clearance, also known as efferocytosis (from Greek effero, meaning to “bury” or “take to the grave”). Apoptotic cells are frequently observed at sites of ongoing inflammation, and their inefficient removal can lead to secondary necrosis and the release of their cellular contents, which can further fuel the inflammatory process. At the same tme, metabolites released by apoptotic cells, also referred to as ‘good-bye’ signals, elicit cellular responses that actively promote resolution of inflammation and tissue regeneration, which is essential for the maintenance of immune ‘silence’.

We aim to address the following questions:

Who are the phagocytes in inflamed tissues?
What are they “eating” (infiltrating leukocytes, dying tissue resident cells)?
How does modulation of efferocytosis pathways impact disease parameters?

In other words, who are the “cleaning crew” and what “tools” they use?

Answers to these questions can uncover novel pathways that can be targeted for therapeutic benefit in inflammatory diseases.

Project 1

Function of the engulfment regulator ELMO1 in inflammation.

Cell clearance regulator Engulfment and cell motility protein-1 (ELMO1) contributes to neutrophil recruitment in arthritis, but is not required in several other inflammatory states, including lung and peritoneal inflammation. This project aims to understand the cues and mechanisms that elicit neutrophil recruitment in an ELMO1-dependent manner.

ELMO1 function in innate immunity.

ELMO1 is highly expressed in cells of the innate immune system. This project is aimed at discovery of molecular mechanisms by which ELMO1 contributes to specific functions of macrophages (phagocytosis, cytokine production), neutrophils (migration, adhesion, degranulation, phagocytosis) and mast cells (degranulation, cytokine production, phagocytosis).

Project 2

Project 3

Efferocytosis modulation in acute and chronic inflammatory disease.

Using models of rheumatoid arthritis, multiple sclerosis, lupus, kidney injury and fibrosis, we aim to discern how targeted modulation of efferocytosis pathways (to decrease or increase efferocytosis efficiency) can be exploited for better understanding of disease etiology and discovery of new therapeutic opportunities.