Timothy Hamill
Pronouns: he/him
Research Mentor(s): Swati Bhattacharyya
Research Mentor School/College/Department: Internal Medicine, Rheumatology / Medicine
Program: UROP
Session: Session 1 (9:00am – 9:50am)
Authors: Timothy Hamill, Swati Bhattacharyya
Abstract
Systemic scleroderma is a chronic autoimmune disorder where scar tissue builds up in the skin, and later the internal organs. Triggering Receptor Expressed on Myeloid Cells (TREM-1) is a transmembrane protein on myeloid cells. It is involved in the inflammatory response of various diseases. Various ligands bind to TREM-1 to induce the signaling cascade, leading to the phosphorylation of DAP12, which activates tyrosine kinase. This enzyme helps produce growth factors like cytokines which are involved in the pathogenesis of systemic scleroderma. It is thought that inhibiting TREM-1 could help treat systemic sclerosis. This study focuses on the effects of TREM-1 inhibitors on the symptoms of systemic sclerosis. Mouse models were used to evaluate therapeutic potential in human patients. Mice used included wild type, and mice treated with bleomycin to simulate systemic sclerosis. Different TREM-1 inhibitors were used to test the effectiveness of each. The results showed that there was significant improvement in regards to increased white adipose tissue presence and decreased collagen production compared to the untreated bleomycin group. However, the wild type still had significantly more WAT presence and less collagen production than the inhibitor groups. Skin biopsies from human patients will be used to further evaluate the effectiveness of different TREM-1 inhibitors. While TREM-1 itself is required for protective immune functions, inhibiting various ligands from binding to it may be valid treatments for diseases such as systemic sclerosis. However, further studies are needed to better understand the nature of the ligands that bind to TREM-1, along with the mechanisms of its signaling cascade.
