Researcher Database
Dr. David Koppstein
Moorenstr. 5
40225 Düsseldorf
Program
Molecular Diagnostics, Early Detection, and Biomarker Development (MDEB)
Summary
DKTK Junior Group Leader for Cancer bioinformatics und multiomics: Targeting subclonal genetic heterogeneity in cancer at the single-cell level
Dysregulation of fundamental transcriptional processes such as splicing is a widespread phenomenon in cancer, affecting diverse malignancies from medulloblastomas to leukemias. These profound perturbations remain a poorly characterized but important phenomenon whose study may yield several benefits, including improved cancer classification, detection of neoantigens for precision cancer therapy, and the possibility to correct misspliced transcripts with oligonucleotide therapy. Our group aims to comprehensively characterize the transcriptional landscape of these cancers using single-cell and third-generation sequencing technologies, yielding insight into the specific molecular pathways affected by these far-reaching mutations.
We also aim to understand the unique mutational signatures arising from driver mutations in specific cancers. Using single-cell multiomic approaches to characterize structural variants, SNVs, and transcription, we hope to comprehensively reconstruct the clonal evolution of cancers with unique "fingerprints" such as recombination signal sequence breakpoints or hyperdiploidy in different types of ALL. These analyses will yield a better understanding of the order of events leading to transformation. In order to pursue our studies we take a holistic approach, working at the interface of bioinformatics and multiomic assay development and collaborating closely with our clinical and experimental colleagues at DKTK/DKFZ and Uniklinik Düsseldorf.
DKTK Junior Group Leader for Cancer Systems Biology
Single-cell approaches have not only revealed a wide variety of cell states, characterized by cells exhibiting striking differences in their transcriptional profile, but have also illuminated the mechanisms underlying state transitions in health and disease. Cellular plasticity and adaptive state changes have recently emerged as a basis for therapeutic resistance in cancer, and a better understanding of how cell state transitions are regulated is critical to develop therapeutic approaches that can overcome therapy resistance.
Our research focuses on understanding the mechanisms driving non-genetic cellular heterogeneity and therapy resistance in malignancy. Using novel single-cell sequencing approaches, we seek to develop new experimental and computational strategies to define altered cell states in both, cancer and immune cells. Our aim is to leverage a data driven strategy combined with single cell genomics and systems biology to address the challenges posed by heterogeneity in cancer, and to develop new strategies to overcome it, with the aim of translating laboratory-based findings into the clinic.