strategies

1

The CRISPR/Cas9-based genome-wide, loss-of-function screens targeting signaling pathways.

Enhancer and suppressor screens to comprehensively identify pathway components.
Synthetic screens to identify the genetic vulnerabilities of cells carrying mutations in human oncogenes and tumor suppressor genes.
Screens based on complex, physiological read-outs of signaling, such as differentiation.

2

Protein biochemistry: proteomics, structure-guided analysis, activity-based purification and cell-free reconstitution of signaling reactions in extracts and using purified components.

3

Chemical Biology: new probes to assay the interactions between proteins and small molecules.

4

Imaging: Live-cell imaging with innovative optical probes and genetically-encoded reporters to monitor the temporal and spatial progression of signaling, the quantitative phase separation behavior of proteins, and the dynamic, signal-regulated trafficking of proteins.

5

Active collaborations: Onn Brandman, Stanford (biomolecular condensates in cancer)

Christian Siebold, Oxford (structural and mechanistic analysis of Hedgehog pathway components)

Douglas Covey, Washington University (synthetic chemistry)

Jan Carette, Stanford (genetic screens)

L. Aravind, NIH (protein and genome evolution)

Fernando Bazan (protein structure modelling and function prediction)

Cecilia Lo, Pittsburgh (heart development and heart defects)

Teresa Gunn, McLaughlin Institute (mouse genetics)

Dario Alessi, University of Dundee