Laurie Parker, PhD

Associate Professor, and Biophysics Department of Biochemistry, Molecular Biology

Laurie Parker

Contact Info

llparker@umn.edu

Office Phone 612-624-9066

Office Address:
7-140 MCB
420 Washington Avenue SE
Minneapolis, MN 55455

Associate Professor, and Biophysics Department of Biochemistry, Molecular Biology

Faculty, PhD Program in Biochemistry, Molecular Biology and Biophysics

Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)


Summary

The Parker Lab is interested in assay development for post-translational modifications (PTMs), with a focus on protein phosphorylation by tyrosine kinases.

Expertise

Post-translational modifications

Research

Research Summary/Interests

Our research program is broadly directed at assay development for post-translational modifications (PTMs), with a focus on protein phosphorylation by tyrosine kinases. Protein tyrosine kinases play key roles in disease and are particularly important in cancer: mutations in several protein tyrosine kinase genes have been identified as drivers of many tumor types and drugs targeted at inhibiting these enzymes represent ~20% (>$9 billion) of the current oncology market. We use a “decoy” substrate biosensor approach (funded initially by a K99/R00 award from the NCI) in which an artificial, optimized substrate peptide is designed to report the activity of a specific enzyme in living cells. Delivery is achieved using cell-penetrating peptides, and enzymatic modification is measured using a range of readout strategies—some that require extraction of the cell contents and some that leave the cell intact. Targeting the function of the enzyme in its intracellular environment preserves protein-protein interactions, localization, and scaffolding-dependent activation, and decoy substrates provide a snapshot of enzymatic activity that circumvents the need for pre-knowledge of every endogenous substrate site. We also develop multiplex-compatible readouts, so we can use a suite of biosensors for different enzymes in order to profile pathways. We have established our approach and laid the groundwork of a substrate development workflow to expand our repertoire of biosensors for kinases and other enzymes. Long term, our lab will maintain a pipeline of biosensor and read-out technology development while also taking an active role in studying signaling biology with our tools.