Structure and Function, Chemical Biology and Therapeutic Targeting of Protein Tyrosine Phosphatases
(1) Molecular Basis of PTP Substrate Recognition and Catalysis
Mechanistic and structural studies with physiological substrates (i.e. phosphoproteins) and regulatory proteins, site-directed mutagenesis, X-ray crystallography and CryoEM,
H/D exchange-mass spectrometry to probe protein recognition, dynamics and interaction.
(2) Activity-based and Interaction Proteomics
Mechanism-based probes to profile PTPs in both normal physiology and pathological conditions. Isolation, identification, and characterization of PTP substrates/regulators.
(3) Chemical Biology and Drug Discovery
Structure-based design, fragment-based library synthesis, high throughput screening and selectivity profiling to acquire potent and selective PTP inhibitors as tools to
modulate PTP functions and leads for therapeutic development.
(4) Roles of PTPs in Signaling and in Diseases
We use state-of-the-art molecular and mouse genetic techniques (e.g. CRISPR gene editing, siRNA silencing, and gene knockout) to define the roles of PTPs in normal physiology
and in diseases.