Date Posted
Speaker
Fahriye Duzagac, Ph.D.
Division of Cancer Prevention & Population Sciences Cancer Prevention Research Training Program (CPRTP) Postdoctoral Fellow
Department of Clinical Cancer Prevention
MD Anderson Cancer Center
Date of presentation: Friday, March 22, 2024 | 12pm EST
Fahriye Duzagac is a postdoctoral researcher at MD Anderson Cancer Center, focusing on cancer prevention, especially in Lynch Syndrome and mismatch repair-deficient cancers. Her undergraduate works included studying cancer stem cells and immune cells within tumor microenvironments using a microfluidic chip-based model to address tumor heterogeneity. Fahriye’s research encompasses two primary objectives: deciphering the molecular and cellular mechanisms of colorectal cancer with an emphasis on immune prevention, including analyzing immune responses in Lynch Syndrome and tracking the transformation from pre-cancerous lesions to invasive colon cancer. Additionally, she is identifying and validating recurrent frameshifted peptide neoantigens in Lynch Syndrome through extensive genomic and transcriptomic analyses and studying the clonal dynamics of neoantigen-specific T cells, key for developing preventive vaccines and improving early cancer detection. Her dedication to this field has been recognized with the CPRIT Postdoctoral Fellowship in Cancer Prevention, and more recently, her selection as an NCI-DCP Early Career Scientist.
Abstract:
Lynch Syndrome (LS) is a hereditary condition marked by mutations in mismatch repair genes, leading to a high risk of colorectal (50-80%) and endometrial (40-60%) cancers, among others. These mutations generate neoantigens, triggering an immune response even in pre-cancerous lesions. Our single-cell omics analysis of LS carriers' colonic tissue revealed a robust immune presence, with T-cell activation and differentiation evident. However, our findings also indicated signs of T-cell exhaustion and dysfunction in active cancer stages, underscoring the critical need for early detection and timely intervention. We explored the potential of neoantigen-based vaccines by identifying and testing immunogenic neoantigens, with a 65% validation rate. Our ongoing research focuses on the immune responses of these neoantigen-specific T cells, aiming to develop TCR-based immune monitoring and vaccination strategies for early cancer interception in LS carriers. This approach could significantly impact the management and prevention of cancer in this high-risk population.
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