Matthew K. Howard

PhD Candidate, UCSF | GPCRs | Functional Genomics | Structural Biology | Pharmacology

Last updated: December 2025

About

I develop and apply high-throughput experimental platforms—primarily deep mutational scanning—to understand GPCR function, pharmacology, and evolution at single-residue resolution. I integrate these approaches with structural biology, molecular simulation, and cell biology to reveal how receptors sense their environment and respond to drugs.

I'm currently a PhD candidate at UCSF working in the Coyote-Maestas and Manglik labs where I collaborate broadly across disciplines including statistics, machine learning, and various "-omics" approaches.

Before UCSF, I graduated from Washington University in St. Louis with degrees in chemistry and biology. At WashU, I worked in the Jackrel lab studying protein disaggregases and amyloid biology.

Find me here: email · Bluesky · Twitter/X · GitHub · LinkedIn · Google Scholar · ORCID

Research

Proton-sensing GPCRs

How do cells detect changes in pH? I used deep mutational scanning of GPR68 to map the complete sequence determinants of proton sensing, combining multiphenotypic screening of both expression and function to identify a conserved polar and charged network that acts as a molecular pH sensor. Together with cryo-EM structures, molecular simulation, and pharmacology, this work revealed how evolution has tuned GPCR sensitivity to extracellular acidification—relevant to inflammation, ischemia, and cancer biology. Published in Cell (2025).

Deep Mutational Pharmacology

I extended GPCR-DMS to Gαi-coupled receptor signaling, using the μ-opioid receptor as a model system to map how every residue contributes to ligand efficacy and potency across diverse chemical matter—from morphine to fentanyl to other synthetic agonists. By comparing mutational effects across compounds, I'm uncovering the distinct residue networks that govern receptor activation for each drug class, with the goal of informing the design of safer analgesics. Manuscript in preparation.

Publications

Google Scholar may be more current. Please Email me if paywalls get in your way.

Highlighted

Howard MK, Hoppe N, Huang XP, Mitrovic D, Billesbølle CB, Macdonald CB, Mehrotra E, Rockefeller Grimes P, Trinidad DD, Delemotte L, English J, Coyote-Maestas W, Manglik A (2025) Molecular basis of proton-sensing by G protein-coupled receptors. Cell. https://doi.org/10.1016/j.cell.2024.11.036

PhD work at UCSF

From WUSTL

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