PhD candidate 'Unraveling Leukemic Transformation in DDX41-Mutant Acute Myeloid Leukemia'

• Application Deadline: April 24 2026
• Nijmegen
• On-site

Job Description

Job description

Project description

Are you an ambitious and curious researcher eager to make a meaningful impact in cancer biology We are seeking a highly motivated PhD candidate to join an exciting project aimed at understanding the mechanisms driving acute myeloid leukemia (AML) in individuals with germline DDX41 mutations.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by impaired differentiation and uncontrolled proliferation of hematopoietic stem and progenitor approximately 5-10% of the cases inherited mutations in the RNA helicase gene DDX41 are found. Carriers have a lifetime leukemia risk of 50 to 75%.

Despite this strong genetic predisposition the mechanisms underlying leukemic transformation remain poorly understood. DDX41-mutant AML presents a unique clinical paradox: disease onset typically occurs later in life and is accompanied by relatively few additional somatic mutations suggesting alternative drivers beyond classical genetic events. It remains unknown why some carriers develop leukemia whereas other do not. Understanding the underlying mechanisms may provide possibilities for clinical intervention and prevention of leukemia development.

In this KWF-sponsored PhD project you will investigate the biological processes that trigger leukemic transformation in individuals carrying germline DDX41 mutations. You will explore both cell-intrinsic mechanisms (e.g. altered gene expression and differentiation programs) and cell-extrinsic factors (e.g. cytokines and circulating proteins) that may contribute to disease initiation and progression.

You will work at the forefront of translational hematology combining patient-derived data with advanced molecular and computational techniques including:

Clonal evolution analysis to trace disease development in individuals with and without AML

Plasma proteomics to identify systemic factors influencing transformation

Stem cell modeling to study dysfunctional DDX41 in controlled settings

Single-cell RNA sequencing to dissect cellular heterogeneity and gene expression changes

You will be appointed as a PhD candidate for a period of four years starting around July 2026. During your PhD you will design and perform laboratory experiments conduct (bioinformatic) data analyses write scientific manuscripts and present your findings at lab meetings and (inter)national conferences. You will also contribute to student supervision and actively participate in team meetings.

Throughout the project you will collaborate closely with an interdisciplinary team of molecular biologists and hematologists. Your PhD trajectory will culminate in the writing and defense of your PhD thesis.

Techniques and skills

During your PhD you will gain hands-on experience with a wide range of molecular and cellular biology techniques including:

Culturing hematopoietic stem and progenitor cells to assess proliferation and differentiation

DNA cloning and bacterial transformation

Cell transfection viral transduction and CRISPR-Cas9-mediated gene editing

(Quantitative) RT-PCR

Flow cytometry

Western blotting

Next-generation sequencing techniques

Mass spectrometry and associated bioinformatic analyses

This project offers an excellent opportunity to develop both experimental and computational skills in a dynamic and translational research environment.

Place of work

The Laboratory of Hematology is part of the Department of Laboratory Medicine at Radboudumc and comprises several research groups as well as an extensive diagnostic laboratory. Research within the lab focuses on both blood cancers and bleeding disorders creating a dynamic and collaborative environment at the interface of research and clinical diagnostics.

As a PhD candidate you will work closely with fellow PhD students BSc/MSc students technicians postdoctoral researchers and clinical hematologists from the Department of Hematology. Together we will design a personalized training and development plan tailored to your interests and career goals.

At the department of Laboratory Medicine you work on high quality diagnostics in hematology clinical chemistry and medical immunology. From a central laboratory you provide fast and reliable results 24/7. With your expert diagnostic work you support healthcare providers within and outside Radboudumc and contribute to the safe and effective treatment of patients.