Thomas Michiels
Doctoral fellow
- Department of diagnostic sciences (Faculty of Medicine and Health sciences)
- Department of biomolecular medicine, Center for Medical Genetics Ghent (Faculty of Medicine and Health sciences)
Principal investigator: prof. Bart Vandekerckhove (MD, PhD)
Co-promotors: prof. Björn Menten (PhD), prof. Karim Vermaelen (MD, PhD) & prof. Filip Van Nieuwerburgh (PhD)
Research focus
Immune checkpoint inhibitors (ICBs) have significantly advanced lung cancer treatment. However, durable clinical responses remain limited to a subset of patients, partly because ICBs rely on spontaneous tumor-specific immune responses. Personalized cancer vaccines targeting neoepitopes offer a complementary strategy by aiming to actively direct T cells against tumor cells and establish long-lasting immunological memory.
Neoepitopes are tumor-specific antigens that can arise from somatic mutations acquired during tumor development. Current neoepitope vaccine design relies on bulk genomic and transcriptomic sequencing to identify and prioritize these targets. However, bulk sequencing provides limited information on how neoepitope expression is distributed across individual tumor cells, potentially overlooking clinically relevant subpopulations such as proliferative, metastatic, or therapy-resistant cells.
My PhD project aims to optimize neoepitope vaccines by integrating both genetic and transcriptional tumor heterogeneity into neoepitope selection. Using full-length single-cell RNA sequencing (Smart-seq3xpress), we characterize transcriptionally distinct tumor subpopulations and investigate neoepitope expression at a single-cell resolution. We aim to improve the selection of true tumor-wide neoepitopes and complement these with neoepitopes targeting specific tumor subpopulations, increasing tumor coverage and potentially reducing the risk of immune escape.
My second focus is expanding the targetable antigen repertoire beyond mutation-derived neoepitopes, which is especially relevant for patients with few suitable conventional neoepitopes. We have developed a multi-omics pipeline to identify non-canonical neoepitopes arising from e.g., alternative splicing, cryptic open reading frames, and gene fusions. Together with CellGENTherapies (UZ Gent), we aim to translate these advances into cancer vaccines and broaden the patient population that may benefit from this strategy.
Biography
- Master of Science Biomedical Sciences: Medical Genetics
Contact & links
- Lab address: campus UZ Gent, MRB2 (entrance 38), Corneel Heymanslaan 10, 9000 Ghent
- Thomas Michiels is interested to receive invitations for presentations or talks