Award: Elizabeth D. Mellins Memorial Fellowship
Biography: Dr. Kathryne Marks is an Instructor at Brigham and Women’s Hospital and Harvard Medical School. She completed her PhD in Microbiology and Immunology at Rosalind Franklin University of Medicine and Science examining the molecular regulation of Th17 cells. She joined the lab of Deepak Rao as a Postdoctoral Fellow in 2021. Dr. Marks’ work during this time has included high dimensional immunophenotyping of blood from patients with rheumatoid arthritis, psoriatic arthritis, and checkpoint inhibitor arthritis as well as expanding on findings from these data with in vitro functional assays. She has also worked to generate synovial organoids of RA synovium in order to improve our understanding of relevant T cell populations and their interactions in the synovium.
This work supported by the ANRF will focus on understanding the T cell responses to TNF inhibitors and other RA treatments and their relation to clinical response. She is excited to further the application of synovial organoids to understand treatment functions including from TNFi and effects on cell-cell communication in RA.
Research Summary: Rheumatoid arthritis (RA) is a common and severe autoimmune disease that imposes a substantial burden on patients in the form of disability, pain, and increased mortality. Several treatments are available for RA, but patients with RA experience highly varied responses to therapy. Only 30% of patients with RA reach a 70% improvement for each treatment, and for those who do respond, treatments can cease to be effective over time. T cells are an immune cell that have been implicated as drivers of RA disease. We hypothesize that heterogeneity of T cell types that are driving disease may explain heterogeneity of treatment response. This proposal seeks to better define the impact of TNF inhibitors on T cell phenotype, to investigate the functions of T cells especially B cell helper T cells in RA joint inflammation, and to identify the impact of TNF inhibitors on their pathogenic functions in synovium. Using an in vitro organoid model of RA joints, we will recapitulate T cell functions and demonstrate the roles of RA treatments on cell interactions. Understanding the specific effects of treatment on different phenotypes of T cells and other immune cells will lead to improved ability to effectively treat disease activity in RA patients by improving our understanding of TNF inhibitor efficacy.
Links:
https://raolab.bwh.harvard.edu/team/
https://connects.catalyst.harvard.edu/profiles/display/Person/195817