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

Collaborations: With experts in structural biology (Christian Siebold, Oxford, Elife 2013, 2016 and Nature 2016), genome-wide screening (Jan Carette, Stanford, Elife and Cancer Research 2016), protein and genome evolution (L. Aravind, NIH, Dev Cell 2014 and 2018), and developmental biology (James Briscoe, Francis Crick Institute, Dev Cell 2018).