Jonathan Ostrem
jonathanostrem.bsky.social
Jonathan Ostrem
@jonathanostrem.bsky.social
Chemical biologist and thoracic oncologist; Assistant Professor and lab PI at #UCSF
Reposted by Jonathan Ostrem
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
Reposted by Jonathan Ostrem
Impressive J. Med. Chem. paper by a team of Revolution Medicines around Adrian Gill and James Cregg. Development of the RAS(On) G12C inhibitor Elironrasib. Exciting to see the evolution of the warhead from disulfide via chloroacetamide and acrylamide to substituted butynamide pubs.acs.org/doi/10....
Discovery of Elironrasib (RMC-6291), a Potent and Orally Bioavailable, RAS(ON) G12C-Selective, Covalent Tricomplex Inhibitor for the Treatment of Patients with RAS G12C-Addicted Cancers | Journal of Medicinal Chemistry
The discovery of elironrasib (RMC-6291) represents a significant breakthrough in targeting the previously deemed undruggable GTP-bound, active KRASG12C. To target the active state of RAS (RAS(ON)) ...
pubs.acs.org
March 17, 2025 at 7:00 AM
Reposted by Jonathan Ostrem
Looking forward to celebrating 80 years of federally funded science, technology and innovation @standupforscience.bsky.social SF, March 7, Civic Center, 1-3 pm 🧪 🧫 🧬
March 3, 2025 at 6:55 PM
Reposted by Jonathan Ostrem
Of the 4000 researchers at NIH, only 20% are tenured. They’re going to fire all the rest as their contracts come up for renewal, absolutely decimating research at the NIH. This is catastrophic, not just for Americans, but for the whole world.

www.science.org/content/arti...
NIH ban on renewing senior scientists adds to assaults on its in-house research
Policy follows firings of tenure-track scientists and suspension of training programs
www.science.org
February 28, 2025 at 6:19 AM
Reposted by Jonathan Ostrem
Federal workers are the people doing the hard work to process veterans’ benefits, make sure our airplanes can fly safely, and protect families from the bird flu.

To all of our federal workers: I see you and I’m fighting for you.
February 28, 2025 at 2:18 PM
Reposted by Jonathan Ostrem
February 27, 2025 at 10:04 PM
Reposted by Jonathan Ostrem
More tragic news about NIH and NIH science. Grant system is frozen and intramural program is being slashed. All will claw back on treatments and cures for cancer and other human diseases. This can’t be what the public wants. 🧪 www.science.org/content/arti...
NIH ban on renewing senior scientists adds to assaults on its in-house research
Policy follows firings of tenure-track scientists and suspension of training programs
www.science.org
February 27, 2025 at 10:05 AM
Reposted by Jonathan Ostrem
Despite court order, NIH grants remain frozen. Newly awarded grants, grants with fundable scores, & funds for a new budget cycle of a current project are all *FROZEN*🥶 and not being released. US research is being choked to death & is on life support right now www.motherjones.com/politics/202...
NIH is again throttling research funding in defiance of a federal court order
A freeze on "new and continuation awards" will "remain in place" pending DEI review, states a new internal memo.
www.motherjones.com
February 26, 2025 at 12:04 PM
Reposted by Jonathan Ostrem
A thread. Things are bad. But we’ve already lost if they smother the passion & joy we have for science. So here’s a proposal: if you’re a biologist in any way impacted by *exasperated wave* & want to chat, drop me an e-mail at myfirst.mylast[at]ucsf.edu. Let’s schedule a 30min chat about [...] (1/n)
February 17, 2025 at 7:00 PM
Reposted by Jonathan Ostrem
NIH funding at @UMich supports important medical research, such as extending the life of organs waiting for transplant, advancing treatments for cerebral palsy, and sustaining experimental genetic trials for children with brain cancer.
February 14, 2025 at 8:25 PM
Reposted by Jonathan Ostrem
Stand Up for Science rallies will be held in DC and state capitals on March 7th. Share with friends. Sign-up here to get email updates with details: www.eventbrite.com/e/stand-up-f...
STAND UP FOR SCIENCE 2025 - DC and NATIONWIDE
Stand up for science with us on March 7th, 2025, because science is for everyone! More info at www.standupforscience2025.org
www.eventbrite.com
February 12, 2025 at 12:44 PM
Reposted by Jonathan Ostrem
Biopharma companies and CEOs are keeping their heads down at their own peril. They should speak up about what’s happening to the NIH and other science agencies before it’s too late.

Silence gives consent. And no one should consent to this.
Stand Up And Be Counted
www.science.org
February 12, 2025 at 4:45 PM
Reposted by Jonathan Ostrem
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
www.biorxiv.org/content/10.1... Activating the tumor suppressor LKB1 through STRAD binding small molecules. Glad we got to help out on this exciting approach from John Gordan’s lab.
Small molecule activation of the tumor suppressor kinase LKB1
The ability to identify and target oncogenic signals has transformed clinical oncology. Drug development for targeted therapies has historically focused on the inhibition of oncogenic kinases and GTPa...
www.biorxiv.org
December 24, 2024 at 12:22 AM