Megan L. Matthews

Megan L. Matthews is an Assistant Professor in the Department of Chemistry at the University of Pennsylvania, School of Arts & Sciences, where she leads an active research group focused on chemical biology and enzymology. Her lab develops innovative chemical proteomics technologies to uncover novel enzyme cofactors and regulatory post-translational modifications, particularly those involving reactive electrophiles, which cannot be predicted from genomic sequences.

• B.S. in Chemistry, Miami University (2005)
• Ph.D. in Chemistry, The Pennsylvania State University (2011)
• Postdoctoral Fellow, The Scripps Research Institute (2012–2017)

Her research centers on the concept of the 'electrophilome'—a largely unexplored half of the reactive proteome. By designing 'reverse-polarity' chemical probes, her group enables the discovery of functionally significant electrophilic modifications in proteins, especially those involved in cancer and Alzheimer’s disease. These discoveries open new avenues for therapeutic intervention through covalent targeting.

The recent publications demonstrate a consistent focus on enzyme mechanisms, cofactor discovery, and chemical probe development. Her work spans from fundamental enzymology (e.g., halogenases, ribonucleotide reductases) to applied chemical biology (e.g., hydrazine probes, chemoproteomic profiling). The keywords across her publications highlight emerging themes in metalloenzymes, radical chemistry, and covalent proteome mapping.

Her scientific contributions have been recognized through prestigious fellowships, including the Merck Helen Hay Whitney Postdoctoral Fellowship. She has published in top-tier journals such as Nature, Nature Chemical Biology, and Journal of the American Chemical Society.

Dr. Matthews advises graduate students and postdoctoral researchers in her lab, fostering a collaborative and inclusive environment. Her lab emphasizes the importance of diverse perspectives in scientific discovery. She has secured research funding to support projects in probe development, target characterization, and disease mechanism studies, particularly in neurodegenerative diseases and cancer.

The Matthews Lab is actively engaged in advancing reverse-polarity activity-based protein profiling (RP-ABPP) for in vivo applications and inhibitor screening. The group collaborates with experts in structural biology, spectroscopy, and disease modeling to translate basic discoveries into therapeutic insights.