Functional Genomics of Acute Leukemias - Baldus’ Lab
Our research is focused on the comprehensive genomic and functional analysis of acute leukemias, with the goal of identifying novel therapeutic targets. We employ integrative high-throughput methods to explore the genomic and epigenetic landscapes of the disease, as well as their impact on gene expression and the resulting clinical phenotypes. To define the functional underpinnings of these observations, we use techniques such as CRISPR/Cas9 genome editing and retroviral overexpression to develop cellular models of key genomic alterations. These models allow us to conduct functional characterizations and pharmacogenomic screenings to uncover potential vulnerabilities for therapeutic intervention.
Our working group is closely involved in the DFG-funded Clinical research unit CATCH-ALL – Towards a Cure for Children and Adults with Acute Lymphoblastic Leukemia (KFO 50/10) with Prof. Claudia Baldus as spokesperson and 3 additional PIs from our lab. Find out more about CATCH ALL here.
Acute lymphoblastic leukemia (ALL)
With this approach we identify and characterize novel disease subtypes within the molecular landscape of B precursor ALL (Bastian L et al. Leukemia 2019 and 2022) and T-ALL (Neumann M et al. Leukemia 2024). We analyze developmental trajectories in ALL leukemogenesis using our transcriptomic reference of normal human B cell development and novel single cell RNA-Seq approaches. These analyses yielded novel molecular subtypes within BCR::ABL1-positive ALL which link the developmental origins to specific patterns of secondary aberrations and clinical outcome (Bastian L, Beder T, Barz MJ et al. Blood 2024). Further research focusses on the interaction of leukemia with the bone marrow micro environment. Based on our pharmacogenomic studies we are heading a clinical trial to explore the efficacy of the BCL-2 inhibitor Venetoclax combined with Blinatumomab in relapsed / refractory ALL (GMALL-BLIVEN, NCT05182385, PI: L. Fransecky).
Acute myeloid leukemia (AML)
Based on our observation of altered epigenetic states in elderly AML patients (Silva P et al. Leukemia 2017), we explore the chromatin landscape of AML patient samples and corresponding cellular models using Hi-C sequencing and RNA-Seq. Based on these analyses, we identified dysregulated PDGFRA expression as a promising therapeutic avenue in IDH-mutated AML (Steinhäuser S et al. Leukemia 2023)
Integrative Bioinformatics
We develop machine learning based approaches for systematic and reproducible analysis of RNA-Seq data. Based on this expertise and representative ALL sequencing cohorts, we have established ALLCatchR - a free R tool for molecular subtype allocation in B precursor ALL (Beder T et al. HemaSphere 2023). We integrate gene expression (bulk and single cell RNA-Seq data) and higher-level multi-omics profiles to define informative models which relate the developmental and functional underpinnings of acute leukemias to clinical phenotypes.
If you are interested in our work or if you wish to apply for a position, do not hesitate to contact us!