Jason Sheltzer
@JSheltzer
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Assistant prof at @YaleMed. Interested in aneuploidy, mitotic kinases, drug targeting, CRISPR, and promoting diversity in science. Co-founder @MelioraTx.
Joined February 2016
Check out our new study in @ScienceMagazine, where we take on a 100-year-old debate: what’s the role of aneuploidy in cancer?. We discovered that genetically removing extra chromosomes blocks cancer growth - a phenomenon we call “aneuploidy addiction”.
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An amazing *randomized trial* on Twitter+academia:. 112 papers were randomly chosen to be shared on twitter by a group with ~58k followers or to not be shared. Papers that were tweeted accumulated 4x more citations compared to non-tweeted papers over 1yr.
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Great new study about science outreach via Twitter: Initially, scientists mostly tweet to each other. But after accumulating about 1000 followers, scientists reach an increasing number of journalists, policy makers, and other members of the public.
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Another scientist whose work initially didn't get the recognition that it deserved - Victor Ambros was denied tenure at Harvard, even after publishing the seminal work that resulted in him receiving the Nobel Prize today!.
BREAKING NEWS.The 2024 #NobelPrize in Physiology or Medicine has been awarded to Victor Ambros and Gary Ruvkun for the discovery of microRNA and its role in post-transcriptional gene regulation.
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Fascinating new preprint on bioRxiv tackles a whale of a question:. Whales are huge. So why don’t they get a ton of cancers?.
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My mom has degrees in biology, chemistry, and medicine, and has more Pubmed papers than I do. Can we *please* drop this sexist standard from science communication?
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I want the US to be a mecca for the world’s scientific talent. If you’re a scientist fighting for a green card, and your research involves cancer, aneuploidy, kinase inhibitors, or anything else that I know a little about, please send me a USCIS letter and I’ll gladly sign it.
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Let’s play a little game. Let’s say that you’re the CSO at a cancer pharma company, and you have to choose a target to go after. Here’s a gene – high expression is associated with poor prognosis in brain cancer. Looks like a good candidate for an inhibitor right?
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In a blinded name-swap experiment, black female high school students were significantly less likely to be recommended for AP Calculus compared to other students with identical academic credentials. Important new paper from @DaniaFrancis:.
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John Jumper went from getting a PhD to getting a Nobel Prize in just seven years!.
BREAKING NEWS.The Royal Swedish Academy of Sciences has decided to award the 2024 #NobelPrize in Chemistry with one half to David Baker “for computational protein design” and the other half jointly to Demis Hassabis and John M. Jumper “for protein structure prediction.”
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Pääbo's father, Sune Bergström, won the Nobel Prize in 1982 for his research on prostaglandins. This is the 8th time the prize has been awarded to the child of a previous winner.
BREAKING NEWS: .The 2022 #NobelPrize in Physiology or Medicine has been awarded to Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution.”
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I swear his chromosomes must be 80% telomere.
Paul Rudd turns 50 today. He’s 30 in the left photo. Nobody ages better than Paul Rudd.
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Our new paper is out today. We used CRISPR to uncover some really striking findings with several drugs and drug targets in clinical trials. Also, we accidentally found the first-ever inhibitor of the cyclin-dependent kinase CDK11.
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14 years ago this month, I started as a PhD student at MIT. Here's what my entering class is doing now:
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Excited to share the launch of the Yale Science Fellows program!. This is a new program for recent PhD grads featuring:.- $90k stipend.- mentored research + research funding.- structured transition to an independent faculty position!. Apply here:
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David Julius’s family fled European anti-Semitism and moved to NYC. Ardem Patapoutian grew up in Lebanon, then immigrated to the US for its educational opportunities. So, they both conducted their Nobel-winning research here. When America welcomes immigrants, we all benefit.
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Academia was built for single people and people whose spouses could easily relocate. How do you rebuild academia to capture the benefits of global idea-sharing while also remaining accessible to two-career families?.
Researchers who move around the world have greater scientific impact than their non-mobile counterparts, a study reports.
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👏👏 Cold Spring Harbor has removed Jim Watson's name from its graduate school. Going forward, its name will be the "The Cold Spring Harbor Laboratory School of Biological Sciences".
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New research from @joans and me on COVID-19: smoking triggers the expansion of a subpopulation of lung cells that express the coronavirus receptor ACE2.
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I’m excited to share that I’ll be joining the Yale School of Medicine as an assistant professor! My lab will be moving from CSHL to Yale this summer. And we’re hiring! If you’re interested in working on cancer genomics, chromosome engineering, or drug targeting, drop me a line.
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Immigrants - including Dr. Karikó - have won about 40% of the Nobel Prizes in STEM that have been awarded to Americans.
BREAKING NEWS.The 2023 #NobelPrize in Physiology or Medicine has been awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.
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In 10 days, the Nobel Prize in Medicine/Physiology will be awarded. Here are the 73 scientists most likely to get woken up by a phone call from Stockholm, based on looking at recent pre-Nobel “predictor” prizes:
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Hey guys - loving #first7jobs! Can we get these trending too?. #NameofFirstPet.#HighSchoolMascot.#MothersMaidenName.#YourZipCode.#Last4ofSSN.
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Out now from @Joans and me - (nearly) everything you know about survival analysis in cancer is wrong.
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Angelika Amon passed away this morning. She was the greatest scientist I’ve ever met. This is a huge loss for her family, her friends, and for every biologist.
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Adjusted for inflation, Trump's '95 tax loss represents more money than the NIH spends on breast, lung, colon, and liver cancer - combined.
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The new class of HHMI investigators average 3.9 papers as corresponding author in Cell, Nature, or Science. 26 out of 26 members of this group previously trained with a PI who is in the National Academy of Sciences or who was an HHMI investigator themselves.
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This year's Nobel Prize on oxygen sensing was awarded for papers published in ~5 different journals. HIF was first identified in a paper in MCB, and its purification was reported in JBC. Groundbreaking work is not determined by a journal's impact factor.
Learn more about the 2019 #NobelPrize in Physiology or Medicine.Press release: Advanced information:
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There may be a fascinating controversy in store for the Nobel Prize this year. One of the awardees, Michael Houghton, previously was awarded but declined to accept the Gairdner Prize because it didn't include two researchers who he felt made key contributions to the discovery:
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Yale has announced an across-the-board raise for postdocs, with salaries for 1st year postdocs starting at $65,000. Plus, the administration is giving PIs extra funding (for one year) to cover funding gaps due to the new policy. Seems like a good step!.
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An interesting trend I found:. Among the top 10 national winners at the Intel/Westinghouse Science Fair from 1990 to 2002, 66% of them are now in academia. Among the same group from 2003 to 2014, less than a third are academics.
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New from my lab: we show that a clinical-stage oncology drug from Eli Lilly is mischaracterized, and its true anti-cancer target is EGFR. We also show how in vitro drug assays can be misleading - cellular+genetic methods are needed to determine drug MOAs.
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In a national survey of postdocs, the only factor found to correlate with life satisfaction was working in a lab with a positive atmosphere. Never underestimate the importance of lab culture! .
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Here are the publication records and research topic areas of 63 faculty candidates in the life sciences who interviewed at R1 institutions in 2019-2020. 70% have a first-author paper in Cell, Nature, or Science, 22% have a K99, and 30% have unpublished work on bioRxiv.
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My lab at Yale can host cancer researchers displaced by the violence. Email me if we can help.
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In two weeks, the Nobel Committee at the Karolinska Institute will award the 2020 Nobel Prize in Medicine/Physiology. Who will win? We don’t know for sure - but I think that we can make some educated guesses.
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The original “Hallmarks of Cancer” – the most cited Cell paper of all time – was published in 2000. In 2011, Hanahan and Weinberg wrote a new version that included four more hallmarks. If you were to update this review for 2020, what “hallmarks of cancer” would you add?
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I think about these results in terms of the “cumulative advantage” theory of inequality: one decision (like taking AP Calc) may not be huge by itself, but a lifetime of being 20% less likely to recommended for honors, promotions, etc. can add up to a lot:
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One week from today, the Nobel Prize in Medicine/Physiology will be announced. Here are the 79 most likely awardees, each of whom has won two or more pre-Nobel “predictor” prizes:
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Very excited to share a new paper from my lab: using a set chromosome-engineering tools, we show that cancers are “addicted” to aneuploidy. If you genetically eliminate single aneuploid chromosomes, cancer cells totally lose their malignant potential!.
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Scientists on twitter trying to improve the culture of academia by calling out bad behavior, encouraging preprints and open-access publications over CNS, supporting research that uses a variety of different model systems, and promoting a healthy work-life balance.
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Next week, the Nobel Prizes will be announced. I don’t know who will win - but I think that we can make some educated guesses about who might:.
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David Julius is an academic 4th-generation Nobel Laureate:. Julius (2021 Nobel) did his PhD under Randy Schekman (2013 Nobel) who did his PhD under Arthur Kornberg (1959 Nobel) who was trained by Carl and Gerty Cori (1947 Nobel) as well as Severo Ochoa (1959 Nobel).
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Wow: thanks to commensal infection with staph bacteria, most people have pre-existing antibodies against commonly-studied Cas9 proteins. This may cause a significant hurdle to using CRISPR in the clinic.
Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans #bioRxiv.
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If I look by gender, there's a really striking difference: our entering class was 48% women, but all 6 of the people who are currently PI's are male.
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Some background: one of the best ways to collect real-world evidence of discrimination is through name-swapping "audit" studies. In these experiments, people are presented with job applications, resumes, mortgage applications, etc., that are identical except for the name….
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In total, this provides a new model for how big animals avoid cancer - maybe they’re just better at DNA repair than us? As a next step, I’d love to see this validated in an animal model - if you drive high expression of whale CIRBP in the mouse, are they cancer-resistant?
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Another academic making the move from basic to translational research
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As labs reopen, institutions *must* have a mechanism for trainees to report unsafe working conditions. If a PI tries to pack their lab, do you have someone that employees can turn to? Is there someone who can tell Professor Nobel-Graybeard that all 40 PDs can't be in lab at once?.
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The Nobel-winning work was published in EMBO J. (1992), Science (1996), PNAS (1997), Immunity (1999), and JEM (2000). A good reminder that world-changing science isn't limited to a single journal.
BREAKING NEWS.The 2018 #NobelPrize in Physiology or Medicine has been awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.”
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The researchers found that when a transcript showing strong grades was given a black female name, counselors were 20% less likely to recommend them for AP calc compared to an identical but anonymous transcript.
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Verma has received ~$65,000,000 in NIH funding since 1985. Proposal: the NIH should put aside a pot of money equal to the total they gave him (and added to each time a new harasser is named), earmarked to launch the careers of junior women.
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These audit studies have demonstrated significant discrimination in a variety of contexts. For instance, “John” is more likely to be hired than “Jennifer” for a scientific position, even if they have otherwise-identical resumes.
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If you choose to transfer a manuscript between Nature-family journals, you can consult a web page that lists the acceptance rates for 124 journals published by the Springer Nature Group. I haven’t seen this data circulated before, so I copied it to share here:
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Great, except:.- Underage wand-use is illegal. - Deadly spells get you sent to jail for life. - There’s a government-run curriculum to teach proper magic use. - Wands are individually registered to each owner. - The heroes win by repeatedly using a non-violent disarming spell.
"It’s worth remembering that Hogwarts, as an entity, was armed to the freaking teeth." via @HeatherWilhelm
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Two weeks from today, the winner(s) of the 2022 Nobel Prize in Medicine/Physiology will be announced. While we can’t know for sure who will win, we can make some educated guesses about who’s most likely.
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Ribbon diagrams of 9 eukaryotic kinases. A beautiful illustration of why off-target toxicity is pervasive and drug development is such a motherfucking pain. How do you design a molecule that’s 1000-fold selective for one of these and none of the others?
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Some members of the National Academy who were denied tenure: . 1) Victor Ambros. He discovered microRNAs and revolutionized our understanding of gene expression.
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New from my lab: we show that a clinical-stage oncology drug from Eli Lilly is mischaracterized, and its true anti-cancer target is EGFR. We also show how in vitro drug assays can be misleading - cellular+genetic methods are needed to determine drug MOAs.
Online now! Inhibition of a lower potency target drives the anticancer activity of a clinical p38 inhibitor by @Deb_Bhattacharj, @JaweriaBakar, David E. Heppner, @JSheltzer, et al at @YaleMed. @MelioraTx @UBuffalo, and others #chembiol
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What happens to a paper submitted to a top journal?. Among a set of manuscripts sent out for review by Cell in 2018:. -33% were published in Cell.-26% were published in another Cell-family journal.-7% are still under review at Cell.-The median time to publication was 391 days
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Something to remember - Feng Zhang was never selected for Forbes' #30Under30 list, while Elizabeth Holmes was awarded their Lifetime Achievement Prize and then gave the keynote address at the 30 under 30 summit.
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I don't know who needs to hear it, but there is an S. pyogenes Cas9 PAM sequence exactly 4bp downstream of the wild-type allele. .
DNA mutation lets some people live healthily on only 4 hours' sleep
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. in some papers and presentations, biologists will use TCGA survival curves showing that their favorite gene is associated with poor prognosis to argue that their gene is super-important. This is weak evidence. *Prognostic biomarkers are not necessarily strong cancer drivers*.
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A glimpse into our future:. South Korea re-opens its bars and nightclubs. A Covid+ person visits three nightclubs in one weekend. 1500+ people potentially exposed, 27 new Covid cases confirmed. South Korea re-closes its bars and nightclubs.
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Question:. Your PI gives you 10 flasks: 5 with cancer cells and 5 with rapidly-dividing non-cancer cells (ES cells, 3T3's, etc). She then locks you in a very fancy metabolism lab and says, “figure out which ones are cancers”. What experiment(s) should you do?.
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96 years ago, Otto Warburg submitted the following grant application:. "Ich benötige 10000 (zehntausend) Mark", or “I require 10,000 marks”. It was fully funded.
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Very disappointed to see this new paper in @NatureCancer on a clinical trial with “HDAC6 inhibitor” ricolinostat. The paper fails to mention three recent reports demonstrating that this drug exhibits pervasive off-target toxicity.
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Adjusted for inflation, Trump's '95 tax loss is more money than NASA spent sending the rovers Spirit and Opportunity to Mars.
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Among 45 biology faculty candidates, having more Twitter followers is correlated with having more 1st-author publications. This is very clearly a causal relationship: being popular on Twitter proves that you are doing groundbreaking science. I will not be taking any questions.
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The Nobel Prize in Medicine will be announced this coming Monday. You might think that the winner is a secret, but, with some degree of confidence, you can narrow it down to some likely candidates -.
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Here are the funding and publication records of 61 new faculty in the life sciences who started labs at 21 large public R1 universities in 2018-2019. 36% have a first-author CNS paper, 75% have published in a CNS-family journal, and 16% have a K99.
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It seems so out-of-place to be receiving any good news this month, but I’m incredibly grateful to the NIH and NCI for funding my lab’s R01 and I’m excited to (eventually) get started on the work!
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This arrived in the mail this morning. (Perfect timing!). But uhh. what on earth should I do with it?
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These frustrating results underscore the prevalence of implicit biases even among school guidance counselors.
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Rosalind Franklin's 100th birthday is this weekend. I've seen many people claim that she couldn't share the 1962 Double Helix Nobel Prize because she died in 1958. This is false. Dag Hammarskjold won the prize posthumously in 1961. 'No posthumous prizes' wasn't a rule until 1974
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MIT has announced the launch of the Angelika Amon Young Scientist Award, a prize for PhD students at non-US institutions who are tackling unique research questions and have an infectious enthusiasm for discovery science! . Apply here ->
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This new paper used an audit methodology to investigate something different - who gets tracked into an Advanced Placement math class. AP classes are heavily weighed for college admissions, so this choice can have significant ramifications for a student's future.
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Kaelin, Semenza, and Ratcliffe won the 2019 Nobel Prize for discovering how cells sense oxygen. Kaelin previously wrote about how this work would be considered "quaint" and "barely publishable" in today's climate, because it lacked a precise mechanism and had no animal studies:
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Out today in @sciencemagazine: strategies to combat discrimination against women in STEM. Really proud to have co-written this piece along with @CWGreider, Shirley Tilghman, Nancy Hopkins, Joan Steitz, @mclneuro, and many others.
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The applicant’s name is varied to suggest the individual’s race/ethnicity/gender. Think “John” vs “Juan” or “Michael” vs. “Michelle”.
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An important new paper from @alliecmorgan and @aaronclauset investigates the effects of parenthood on academia. In short, women are penalized for becoming mothers, while men aren’t penalized for becoming fathers.
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What does it take to become an HHMI Investigator? I looked at the pub histories and training records of the new HHMI Investigators appointed in 2018. The median PI had 3 last-author papers in CNS when they were selected, and 15 out of 19 were trained in an HHMI or NAS lab.
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Ben Barres, visionary neuroscientist and out-spoken advocate for women in STEM, has died. Ben was trans, and used his own experience transitioning to motivate discussion of the many ways that gender can affect academic careers. A huge loss for science.
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In a cool experiment, they found a region of the genome that was conserved between mouse, human, cow, and whale, and targeted it with CRISPR. They found that the whale cells were more likely to repair the CRISPR breaks in an error-free manner compared to any other species.
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Every time that I get depressed about how cancer research is filled with over-hyped, irreproducible results, I find a news story to read about anti-aging science and suddenly cancer research doesn’t seem so bad anymore. HT @kevinnbass .
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Great to see our work on cancer aneuploidy highlighted on the cover of @ScienceMagazine.
Using modern biological tools, researchers engineered #cancer cells with and without specific chromosome abnormalities, showing how tumors rely on them for survival and clarifying the biological role of aneuploidy. Learn more this week in Science:
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Welcome Tavi Glenn Sheltzer-Smith! Born on 4/21/22. 8 pounds 3 ounces, 21 inches long. Mother and baby are doing great!
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Fascinating paper. Knockout mutations that cause mRNA decay trigger the up-regulation of homologous genes, allowing cells to “compensate” for the LOF alteration. People who do CRISPR experiments will have to wrestle with these findings. Some thoughts….
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And, to everyone out there feeling disappointed about not making the #ForbesUnder30 list, please remember that Feng Zhang was never chosen, while Elizabeth Holmes was awarded the “30 under 30” lifetime achievement prize and gave the keynote address at their conference.
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You can see that other gender/race combinations mostly cluster around 1. But in three of four experiments, the black female student was less likely to be recommended for AP calc compared to the nameless transcript. “Black female” was significant in the pooled analysis as well:
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Jim Allison’s immunotherapy Nobel Prize this week underscores the power of a model organism that has attracted a ton of criticism in recent years:
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Interesting new paper with an important message - normal clone-to-clone variability is an important confounder in CRISPR experiments.
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New from my lab: we discovered that tumors from Black cancer patients exhibit an increased frequency of whole-genome duplication events, and we found that these alterations may contribute to racial differences in patient outcome.
An elevated rate of whole-genome duplication events in cancers from Black patients #medRxiv.
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What drug has the weirdest mechanism-of-action?. Rapamycin has to be up there: it binds to the prolyl isomerase FKBP12, and the rapamycin-FKBP12 complex is a potent and selective inhibitor of the mTOR kinase. What's your favorite weird MOA?.
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Little known fact: Bill Barr has actually been moonlighting at the NIH, and I think his input really improved my last summary statement.
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One Angelika Amon story that’s important to remember: when it was revealed that MIT knowingly accepted donations from sex trafficker Jeffrey Epstein, she stood up at a faculty meeting and called on MIT’s president to resign.
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