Research Summary
The Arandjelovic laboratory research focus is on cell clearance in inflammatory disease, using rheumatoid arthritis (RA) and multiple sclerosis (MS) as model systems. Inflammatory states are associated with high rates of cell death, mostly through apoptosis, and the clearance of apoptotic cells is a critical step in disease pathology. However, the cellular identity of phagocytes and the molecular events that contribute to the clearance of apoptotic cells has been understudied in many inflammatory diseases. In other words, “who” are the cleaning crew and which “tools” are they using?
Project 1
Function of the engulfment regulator ELMO1 in inflammation.
Cell clearance regulator engulfment and cell motility-1 (ELMO1) contributes to neutrophil function in arthritis, but is dispensable in several other inflammatory states, including lung and peritoneal inflammation. In addition, the human ELMO1 single nucleotide polymorphism (SNP) rs11984075, which occurs in up to 25% of the human population, associates with increased neutrophil migratory capacity and higher susceptibility to RA. In this project, we aim to address the tissue specificity of ELMO1 function in neutrophils and identify the consequence(s) of the arthritis-associated ELMO1 rs11984075 on neutrophil functions.
Disease contribution and therapeutic potential of cell clearance pathways in autoimmune inflammation.
Apoptotic cells are frequently observed at sites of ongoing inflammation, and inefficient clearance of apoptotic cells can lead to secondary necrosis and the release of their cellular contents, which can further fuel the inflammatory process. However, the nature of dying cells and phagocytes that clear them remains unclear. The questions that we aim to address in this project include:
Who are the phagocytes in inflamed tissues in RA and MS?
What are they “eating” (infiltrating leukocytes, dying tissue-resident cells)?
How does the modulation of engulfment pathways impact disease parameters?
Collectively, our studies seek to identify new modulators of inflammatory and autoimmune disease and uncover novel pathways that can be targeted for therapeutic benefit.