Developing a platform to characterize and drug protein tyrosine phosphatases.

Our research spans the disciplines of chemistry and biology with an emphasis on protein tyrosine phosphatases (PTPs), enzymes that remove phosphoryl groups from tyrosine phosphorylated proteins and regulate a plethora of cellular processes, including growth, differentiation, metabolism, and the immune response.

Using state-of-the-art molecular, cellular and mouse genetic techniques, we seek to fully characterize the >100 members of the PTP family and understand how PTP activity is regulated to modulate cellular signaling and how PTP malfunction causes diseases. To promote therapeutic application of drugging the PTPs as a target class, we employ fragment-based, and structure-guided medicinal chemistry to develop potent and selective chemical probes (orthosteric and allosteric inhibitors, covalent modifiers, and PROTAC-based small molecule degraders) for PTP functional interrogation, target validation, and therapeutic development. Current efforts aim to advance our target validation and lead generation paradigm and to create a ‘PTP-based drug discovery platform’ that will ultimately impact the therapeutic portfolio of tomorrow.

Our research program is multifaceted and incorporates both established and emerging technologies, across disciplines. Students have ample opportunity to interact with a highly interactive, collaborative and multi-disciplinary group of individuals with expertise ranging from biochemistry, cell biology, mouse genetics, structural biology, mass spectrometry, organic synthesis, medicinal chemistry, chemical biology and in vivo pharmacology.