For the last 5 years, my lab has focused on developing mutational scanning methods and learning how to answer specific questions in protein biology. @matthewkhoward.bsky.social and I wrote a review on experimental decisions and future directions for our nascent field! doi.org/10.1146/annu...

Mechanistic Mutational Scanning to Uncover the Secret Life of Proteins

Deep mutational scanning (DMS) has emerged as a transformative tool for dissecting individual protein function and broader cell biology. DMS methods enable comprehensive interrogation of sequence–func...

annualreviews.org

Happy to see this work out now in Genome Biology! Check out the final version here for your FACS DMS needs: link.springer.com/article/10.1...

Accurate variant effect estimation in FACS-based deep mutational scanning data with Lilace - Genome Biology

Deep mutational scanning (DMS) coupled with fluorescence-activated cell sorting (FACS) provides a high-throughput method to link genetic variants with quantitative molecular phenotypes. Analysis of th...

link.springer.com

Jerome@jeromics.bsky.social · last yr.

Check out our new preprint on Lilace, a statistical tool for scoring FACS-based deep mutational scanning experiments! Lilace directly models the shift between variant fluorescence distributions and provides score uncertainty estimates to better assess reliability and reproducibility. (1/3)

A wonderful first for me at the upcoming @biophysicalsoc.bsky.social meeting in SF is having many lab members present! See 6 brilliant graduate students postdocs from the lab present talks and posters on how they are pushing the boundaries of technology and mechanistic membrane protein biology

Check out Jerome's paper! As we push the boundaries of DMS, it is critical that we develop robust ways to score variant effects--and he is doing just that. Excited to put this to use in our upcoming GPCR-DMS endeavors :)

Jerome@jeromics.bsky.social · last yr.

Check out our new preprint on Lilace, a statistical tool for scoring FACS-based deep mutational scanning experiments! Lilace directly models the shift between variant fluorescence distributions and provides score uncertainty estimates to better assess reliability and reproducibility. (1/3)

We are hiring a #postdoc in the Deshpande lab! Come join us tackle important mechanistic questions in inflammatory signaling. Please share or apply! careers.gene.com/us/en/job/20...

Postdoctoral Fellow - Structural Biology, Deshpande Lab in South San Francisco, California, United States of America | Students & Graduates at Genentech

Apply for Postdoctoral Fellow - Structural Biology, Deshpande Lab job with Genentech in South San Francisco, California, United States of America. Students & Graduates at Genentech

careers.gene.com

Beautiful work from our colleagues in the Jura & Verba labs here @ UCSF! Cryo-EM structures of PI3Ka / KRas complex in context of lipid nanodiscs. Read on for unexpected dimers & to see how high-rez structural biology w/ the right reconstitutions can inform mechanism! www.biorxiv.org/content/10.1...

Structures of the PI3Kα/KRas complex on lipid bilayers reveal the molecular mechanism of PI3Kα activation

PI3Kα is a potent oncogene that converts PIP2 to PIP3 at the plasma membrane upon activation by receptor tyrosine kinases and Ras GTPases. In the absence of any structures of activated PI3Kα, the mole...

biorxiv.org

It is important at this pivotal moment to @standupforscience.bsky.social. Looking forward to sharing my thoughts on why this should be a national priority at tomorrow’s rally in SF:

New preprint! Here, we explore how endocytosis encodes receptor-specific cAMP/PKA signaling downstream of three endogenously coexpressed GPCRs. www.biorxiv.org/content/10.1...

Endocytosis sculpts distinct cAMP signal transduction by endogenously coexpressed GPCRs

Many G protein-coupled receptors (GPCRs) trigger a second phase of G protein-dependent signaling from internal membranes after agonist-induced endocytosis. However, individual GPCRs differ significant...

biorxiv.org

My lab at @stanfordmedicine.bsky.social is recruiting! We are looking for a postdoc at the interface of quantitative proteomics and G protein-coupled receptor (GPCR) biology: postdocs.stanford.edu/prospective/... #TeamMassSpec #Proteomics #GPCR #Postdoc

Congrats @willowcoyote.bsky.social @amanglik.bsky.social and all authors on a tour de force dissection of proton-sensing by GPCRs! DMS, cryo-EM, MD -- it has it all! www.cell.com/cell/fulltex...

Molecular basis of proton sensing by G protein-coupled receptors

Howard et al. combine mechanistic deep mutational scanning, cryo-EM, and constant-pH molecular dynamics simulations to provide a holistic view of proton activation in human pH-sensitive GPCRs.

cell.com

Thanks for the invite! Excited to share some of our recent work tomorrow 😀

Atlas of Variant Effects Alliance@varianteffect.bsky.social · 2y ago

Welcome to the first Variant Effects Seminar Series of 2025! Kicking off on Jan 7 with two amazing speakers: Ujjwal Rathore and Matthew Howard. Don’t miss it! varianteffect.org/seminar-series #FunctionalGenomics #Seminar

Thanks @justingenglish.bsky.social!! Awesome working with you and excited to see where we go in the future 👀

Justin English@justingenglish.bsky.social · 2y ago

Groundbreaking work by @matthewkhoward.bsky.social and Nicholas Hoppe (not on bsky?) from the @willowcoyote.bsky.social @amanglik.bsky.social labs. Mapping function to structure with deep mutational scanning to resolve the mechanisms of pH sensing GPCRs www.sciencedirect.com/science/arti...

Happy New Year! (and first post here 😀) Excited to share the final version of our work where we combine deep mutational scanning, cryo-EM, and molecular dynamics to further resolve the mechanisms of pH sensing in GPCRs. 🧵(1/n) www.cell.com/cell/fulltex...

Happy Thanksgiving y'all! I'm thankful for my whole lab, team, and collaborators this year. Our updated and final version of the TRE MPRA system is online today. If you have time between turkey bites have a gander. rdcu.be/d1OTf

A massively parallel reporter assay library to screen short synthetic promoters in mammalian cells

Nature Communications - Context-dependent, responsive synthetic promoters are crucial for a wide range of applications, yet currently available options are limited. Here, authors develop a library...

rdcu.be