With over 200,000 US cases per year, prostate cancer is the most commonly diagnosed malignancy in men and the second most common cause of male cancer deaths.

We aim to understand lethal prostate cancer and to speed up the search for a cure. While progress in clinical research is naturally limited by the established standards of care, therapy using animal models is not. Model therapy in contrast, is limited by the qualities of the model system. Based on our analysis of human cancer genomes, we have generated a first in kind mouse model for tracking of endogenous metastatic prostate cancer, termed RapidCaP. This system allows for live visualization of metastasis and therapy failure and for molecular/ genetic dissection of these processes.

Our second focus is on the PTEN tumor suppressor. Many cancer types are driven by its partial inactivation. Therefore, we study how the remaining PTEN activity could be supported to restore normal growth control and block cancer.

Postdoc and student positions are available



We have developed the RapidCaP model system for metastatic prostate cancer, which uses surgery for gene manipulation, instead of breeding. This approach offers tremendous flexibility, has drammatically reduced model generation times and allows us to visualize metastatic prostate cancer through live bioluminescence imaging.

We use the system to understand the molecular and genetic evolution of metastasis and therapy resistance and now pursue three major avenues:

- Single cell analysis of metastatic genome evolution

- Novel therapy and biomarkers for translation to human

- Novel technology for metastasis gene discovery


Recent progress

RapidCaP for validation of human metastasis genes - Methods

PIP backbones as markers for p53 mutation- Cell Reports

Myc drives PTEN mutant prostate metastasis - Cancer Discovery

PI 3-K pathway phosphatases and Cancer - Clin Cancer Res

AR target gene amplification in metastasis - Mol Cancer Res

PHLPP1 blocks prostate cancer - Cancer Cell


PTEN Regulation

The PTEN/ PI 3-Kinase enzyme system translates extracellular growth cues into intracellular signals. To achieve this, PTEN turns cell membrane phospholipids into an off-state. This prevents membrane recruitment and activation of growth promoting kinases. Receptor tyrosine kinases revert PTEN function by activating PI 3 Kinase, leading to membrane recruitment and activation of the oncogenic AKT kinase (see snapshots, left).

In spite of its plasma-membrane function, PTEN has been consistently observed in cell nuclei, but mechanism and relevance of this localization have remained unclear. We have originally resolved this paradox by demonstrating that mono-ubiquitination of PTEN is essential for nuclear import, while poly-ubiquitination results in PTEN degradation. Patients harboring a germ line mutation in a PTEN ubiquitination site suffer from inheritable Cowden’s Disease. They develop pre-cancerous lesions, which display nuclear exclusion of PTEN. Since the cytoplasmic mutant retains catalytic activity, we can conclude that PTEN nuclear import is essential for tumor suppression. These findings demonstrate how a comprehensive view of disease initiation can be attained from integration of biochemistry, cell biology and human genetics and give rise to new ideas for combatting cancer.


Recent progress

PTEN funcions on endocytic vesicles - Molecular Cell

p53 mutation dictates PIP lipid tail chain lengths - Cell Reports

PTEN suppression as a natural process - Trends Cell Biology

Ndfip1, a new PTEN regulator in neurons - J Cell Biology