Wanted for the next possible date at the department of hematology, oncology & rheumatology at the university hospital Heidelberg and the DKFZ.

We are looking for a PhD student for our project "Cellular plasticity driven by innate immune activation in DDX41-mediated myeloid malignancies”. This project is part of the SFB/CRC 1709 "Cellular Plasticity in Myeloid Malignancies: From Mechanisms to Therapies” and funded by the Deutsche Forschungsgemeinschaft. Wihtin this CRC, we will focus on new intrinsic and extrinsic factors that enable and regulate cancer cell plasticity in myeloid malignancies. Our overall goal is to pave the way for new cancer therapies.

Inherited mutations in the RNA helicase DDX41 represent the most frequent genetic predisposition to myeloid neoplasms, yet the mechanisms by which they drive disease remain poorly understood. Increasing evidence suggests that both innate immune signaling and alterations in the bone marrow microenvironment critically shape leukemic transformation in these patients. The aim of this PhD position is to investigate how DDX41 mutations in mesenchymal stromal cells (MSCs) mediate inflammation, hematopoietic stem/progenitor cell plasticity (HSPCs), and leukemic transformation. The project will use innovative 2D and 3D HSPC/MSC co-culture models, functional clonogenic and differentiation assays, bulk and single-cell transcriptomics, and multiplex cytokine profiling to dissect stromal–hematopoietic interactions. In addition, the PhD student will assess the therapeutic potential of STING inhibition, alone or in combination with chemotherapy, in patient-derived and experimental model systems. To resolve clonal hierarchies and differentiation states, the project will apply CITE-seq and the CloneTracer pipeline in close collaboration with partner labs, providing a powerful framework to link genotype, phenotype, and microenvironmental context. By integrating functional and molecular analyses, this work aims to uncover microenvironmental mechanisms driving DDX41-mediated myeloid malignancies and to identify new strategies for targeted therapy.