Matt Howard
@matthewkhoward.bsky.social
Doing science @UCSF in the Coyote-Maestas and Manglik Labs. Former Jackrel Lab @WUSTL www.matthewkhoward.com
Pinned
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...
🧵(1/n)
www.cell.com/cell/fulltex...
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 :)
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)
Accurate variant effect estimation in FACS-based deep mutational scanning data with Lilace
Deep mutational scanning (DMS) experiments interrogate the effect of genetic variants on protein function, often using fluorescence-activated cell sorting (FACS) to quantitatively measure molecular ph...
www.biorxiv.org
June 30, 2025 at 4:18 PM
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 :)
Reposted by Matt Howard
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...
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
March 26, 2025 at 11:52 PM
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...
careers.gene.com/us/en/job/20...
Reposted by Matt Howard
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...
www.biorxiv.org
March 26, 2025 at 4:20 PM
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...
Reposted by Matt Howard
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:
March 5, 2025 at 4:54 PM
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:
Reposted by Matt Howard
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...
www.biorxiv.org
February 27, 2025 at 6:14 PM
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...
Reposted by Matt Howard
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
@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
Open Postdoctoral position, faculty mentor Ruth Huttenhain | Office of Postdoctoral Affairs
postdocs.stanford.edu
February 24, 2025 at 8:17 AM
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
@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
Reposted by Matt Howard
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.
www.cell.com
January 2, 2025 at 5:31 PM
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...
Thanks for the invite! Excited to share some of our recent work tomorrow 😀
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
#FunctionalGenomics #Seminar
January 6, 2025 at 8:35 PM
Thanks for the invite! Excited to share some of our recent work tomorrow 😀
Thanks @justingenglish.bsky.social!! Awesome working with you and excited to see where we go in the future 👀
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...
Mapping function to structure with deep mutational scanning to resolve the mechanisms of pH sensing GPCRs
www.sciencedirect.com/science/arti...
Molecular basis of proton sensing by G protein-coupled receptors
Three proton-sensing G protein-coupled receptors (GPCRs)—GPR4, GPR65, and GPR68—respond to extracellular pH to regulate diverse physiology. How proton…
www.sciencedirect.com
January 6, 2025 at 8:01 PM
Thanks @justingenglish.bsky.social!! Awesome working with you and excited to see where we go in the future 👀
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...
🧵(1/n)
www.cell.com/cell/fulltex...
January 6, 2025 at 7:57 PM
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...
🧵(1/n)
www.cell.com/cell/fulltex...
Reposted by Matt Howard
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
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
November 28, 2024 at 6:50 PM
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
rdcu.be/d1OTf