Postdoctoral Fellow

María Camila Tovar Fernández

Profile

My current postdoctoral research work is meant to explore fusion oncoproteins as a source of antigens in B-cell Acute Lymphoid Leukemia. My interest is to uncover molecular mechanisms for CD8+ T cell activation in Leukemia malignancies that contribute to immunotherapies. My academic track started with an industrial microbiology degree at Pontificia Universidad Javeriana. I then moved abroad to study for a master’s degree in cellular biology, physiology, and pathology, specializing in aging at Université Paris Descartes and a PhD in oncogenesis at the Université Paris cité and the University of Gdansk.

Project description

Fusion Oncoproteins: Unlocking Their Potential as AntiTumoral Antigens for CD8+ T Cell-Mediated Response in B-ALL

The discovery of neo-antigens plays a pivotal role in advancing immunotherapies for B-cell Acute Lymphoid Leukemia (B-ALL). Fusion oncoproteins (FOs), arising from chromosomal translocation, are prevalent in B-ALL and often contain intrinsically disordered regions (IDR), leading to phase separation and the formation of aberrant condensates. The involvement of autophagosome and proteasome molecules in the genesis of biomolecular condensates prompts our hypothesis that FOs with IDR can be targeted by the autophagosome or immunoproteasome to generate tumorassociated antigens recognized by CD8+ T cells. For this project, we have defined 3 objectives: i) Investigate the phase separation capacity of FOs and their targeting by antigen processing mechanisms such as immunoproteasome and autophagy machinery, ii) Identify the MHC-I immunopeptidome derived from different FO-driven B-ALL cell lines, iii) Validate that the detected peptides are efficiently targeted by CD8+ T cells and are linked to immunoproteasome and/or autophagy. Our study focuses on six specific FOs (E2A-PBX1, E2A-HLF, PAX5-ETV6, ETV6- RUNX1, BCR-ABL1, and KMT2A-AFF1) frequently expressed in B-ALL and our approach integrates high-resolution microscopy, high-throughput proteomics, and T cell immunogenicity assays. Identifying neo-antigens originating from FOs that form condensates, is crucial for immunotherapy, as these proteins not only signify aberrant cellular processes but also offer potential targets for precise and personalized cancer treatments, harnessing the power of the immune system against specific tumor signatures.

Free keywords: B-ALL, Neo-antigens, Fusion oncoproteins, MHC-I antigen presentation