Project 2022-041: Investigation of the role of SRSF1 in innate immune functions and the development of autoimmunity

  • Therapeutic Area: Dermatology; Immunology & Inflammation
  • Technology Platform: Gene Therapy & Editing
  • Development Stage: Concept (Early Opportunities)

Abstract

Psoriasis is a skin autoimmune disease which commonly leads to psoriatic arthritis and is characterizedby a complex immunopathogenesis. Serine and Arginine Rich Splicing Factor 1 (SRSF1) is a splicing factor that binds to exonic enhancers and stimulates splicing and is previously implicated with auto-inflammatory diseases. Using acute viral infection models, we uncovered a role of SRSF1 in the regulation of CD11B+LY6C+ myeloid derived suppressor cells. To follow up on these observations we generated a novel transgenic mouse to investigate the role of SRSF1 in myeloid cells which currently remains unexplored. Our experiments will focus on the role of SRSF1 in innate immune functions and the development of autoimmunity using various in vivo gene transfer models that we have developed in house and result in epidermal hyperplasia and joint inflammation, clinically resembling psoriatic arthritis. We will investigate the role of SRSF-1-IL-17A in autoimmunity using in vivo models of psoriatic arthritis where the pathology of skin and joints can be examined. Using loss of function and gain of function transgenic mice we will analyze using spectral cytometry and single cell RNAseq the effect of SRSF1 deletion in autoimmunity and tolerance. Next, we will investigate the mechanistic aspects of myeloid SRSF1 deletion in neutrophils and osteoclasts which are responsible for skin inflammation and bone resorption respectively. The results from this study will inform new treatment options and overall improved clinical outcomes for psoriatic arthritis patients.

Contact Information

Name: Stan Mah

Email: smah@bidmc.harvard.edu

Phone: 617-667-0573