Understanding Metastasis – Designing models of lethal cancer
We have developed the RapidCaP model system for metastatic prostate cancer. It uses surgery for gene manipulation in the prostate. This approach allows us to visualize and probe metastasis biology in the fully native and immune competent setting. We use it to define the stepwise progression from primary tumor escape to colonization of metastatic sites such as bone, liver and brain. This research is boosted by the use of single cell genome analysis and our recent adaptation of microscopy for whole organ imaging at single cell resolution.
Publications and Press:
– Whole organ imaging of metastasizing prostate cancer at single cell resolution
– RapidCaP original publication: Myc drives PTEN mutant prostate metastasis
– IL6 and Myc activation in metastatic prostate cancer - Cancer Discovery
The Neuro-Metastasis Interface
A major challenge in metastasis research is the identification of factors that control progression of non life-threatening tumors to lethal metastatic disease. In spite of much knowledge on the role of tumor neuron interactions in primary prostate cancer, the role of neurons in metastatic prostate cancer remains to be defined. We recently developed whole organ imaging of metastatic tumors in their native environment. Now we map and manipulate interactions between the peripheral nervous system and metastatic lesions in collaboration with neuroscientists at CSHL.
Publications and Press:
– Next Directions in Cancer Neuroscience - Cancer Discovery 4/2024
– Review: Roadmap for the emerging field of Cancer Neuroscience
– Interview in Nautilus Magazine
Therapy of Lethal Prostate Cancer
We use the RapidCaP model to understand evolution of metastasis and therapy resistance. We combine three major approaches to study novel therapy approaches
- Single cell analysis of metastatic therapy resistance
- Dietary control of prostate cancer progression
- Discovery of therapeutic targets in genome wide screens
Publications:
– A new approach to target MYC and metastasis - J Cell Biology
– Metformin, mitochondria and prostate cancer - Cell Reports