Postdoctoral Researcher – Molecular Drivers of BRCA-Related Precancer

Postdoctoral Researcher – Molecular Drivers of BRCA1-Related Precancer About the job

We are recruiting a postdoctoral researcher to join a newly funded Gray Foundation Team Science project tackling one of the most important unsolved problems in cancer prevention: what drives the very first steps of breast cancer initiation in BRCA1 mutation carriers. Working at the interface of human tissue biology, single-cell genomics, spatial imaging, and functional mouse modeling, you will help map the genetic and phenotypic landscape of BRCA1-deficient precancerous cells in prophylactic mastectomy specimens and translate those discoveries into functionally validated driver candidates – a unique opportunity to do science that directly connects to clinical cancer interception.

The Jonkers laboratory at the Netherlands Cancer Institute has built a world-leading platform for functional breast cancer modeling, combining germline genetics, intraductal somatic engineering, and quantitative in vivo imaging. We are now applying that platform to study the biology of BRCA1-associated precancer and are looking for an exceptional postdoctoral researcher to lead this work.

You will work with a novel mouse model that combines germline heterozygous Brca1 deficiency with a dual-color fluorescent reporter that marks cells undergoing Cre-mediated loss of heterozygosity (LOH) in real time. Our preliminary data show that Brca1 LOH cells are actively cleared from the ductal epithelium in vivo, and this clearance is rescued by Trp
53 loss. This provides a quantitative and mechanistic benchmark for ranking candidate perturbations.

Candidate driver genes will be introduced somatically at low frequency in mice – closely resembling the occurrence of early mutations in BRCA1 mutation carriers – through intraductal delivery of high-titer lentiviruses encoding Cre with cDNAs for over-expression or CRISPR guides for loss-of-function. Candidates will be prioritized from human precancer genomic data and from in vitro functional genetic screens. The readout will be whole-mount imaging of entire mammary glands of our mouse model, at single-cell resolution.

This enables quantification of clone persistence, expansion, and progression to early lesion formation across the full gland. In parallel, you will investigate how immune-epithelial interactions in precancerous ducts impact clonal persistence and tumorigenesis.

Science is at the heart of everything we do at the NKI. But breakthroughs don't happen through science alone; they happen through people – curious minds, bold thinkers, people who challenge assumptions and turn complex questions into meaningful discoveries. Around 600 scientists, together with 150 scientific and 150 administrative professionals, work here across the full spectrum of cancer research, from fundamental science to clinical innovation.

With roughly 55 nationalities represented, we form a vibrant international community where English is our shared language and every voice carries equal weight. Our institute sits just 15 minutes by bike from the heart of Amsterdam.

You will be working at the intersection of genetics, cell biology, and cancer immunology, within a collaborative multi-laboratory environment. The ability to communicate across those boundaries, and to take ownership of a project while contributing generously to those around you, is essential. Furthermore:

• You hold a PhD in Cancer Biology, Cell Biology, Molecular Biology
  , or a closely related discipline
• You are a rigorous, analytical, and quantitative scientist with a genuine interest in mechanistic in vivo research
• Experience with mouse models, lentiviral systems, CRISPR
  , or mammary gland biology is an advantage
• Intellectual curiosity and experimental precision matter more than experience with any specific technique
• You think critically about experimental setups and how to address scientific questions effectively
• You enjoy reading across disciplines and integrating insights from different fields
• You are comfortable with the iterative nature of in vivo research