Dr. Jonas Becker

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Research Project

Data-independent acquisition mass spectrometry for the detection of tumor-specific neoepitopes

Presentation of tumor-specific peptides by HLA class I molecules to CD8+ T cells is the foundation of epitope-centric cancer immunotherapies, such as therapeutic vaccines or TCR-transgenic T cells. Currently, the only available technique to provide a direct proof of actual peptide presentation at the cell surface and thus of actionable targets is mass spectrometry-based immunopeptidomics.
Our laboratory has previously developed a highly sensitive targeted nanoLC-MS workflow which will be further utilized in cooperation with clinical partners for the detection of tumor-specific, often low abundant, neoepitope candidates predicted from next-generation sequencing data.
Additionally, the aim of this project is to establish a data-independent acquisition (DIA) strategy for immunopeptidomics. In DIA, all peptides within a defined mass/charge window are subjected to fragmentation in an unbiased manner generating highly convoluted mass spectra. This process is iterated across the complete mass/charge range in order to generate a "digital map" of the analyzed sample. Albeit not expected to be as sensitive as the already established targeted workflow, DIA analysis of tumor material will allow us to investigate the presentation of a broader neoepitope candidate panel, including those arising from non-canonical sources such as bacterial peptides, translation from alternative open reading frames or peptides originating from alternatively spliced transcripts. Moreover, DIA analysis will be used to explore the immunopeptidome as a whole to gain insights into antigen processing and presentation and to elucidate the effect of perturbations such as drug treatments or altered gene expression on the presented immunopeptidome in order to identify vulnerabilities of cancer cells.

Scientific CV

since Aug 2024
Senior Scientist, Immunotherapy and Immunoprevention, DKFZ, Heidelberg

Sep 2021 - Aug 2024
Postdoctoral Scientist, Immunotherapy and Immunoprevention, DKFZ, Heidelberg

2016 - 2021
PhD Student, Research Group for Diseases of mRNA Metabolism (Prof. Andreas E. Kulozik & Prof. Matthias W. Hentze), Molecular Medicine Partnership Unit, Heidelberg

2016
Research Assistant, BioMedX GmbH, Heidelberg

2013 - 2016
MSc Molecular Biotechnology, Ruprecht-Karls-University, Heidelberg
(including a research stay at the McKnight Brain Insitute, University of Florida, Gainesville, USA)

2010 - 2013
BSc Molecular Biotechnology, Ruprecht-Karls-University, Heidelberg