David Shechter

Jack Smith: "My fear is that we have seen the rule of law function in our country for so long that many of us have come to take it for granted. The rule of law is not self-executing. It depends on our collective commitment to apply it."

Reminder for those applying for #NIH grants using the #ScienCV templates. You can format the text sections using html codes:
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How does PRMT5 link splicing to mRNA export?

Out in Mol Cell: by methylating Sm proteins, PRMT5 releases mRNAs that would otherwise remain trapped on chromatin.

Meet GRIPPs: Genomically Retained Incompletely Processed Polyadenylated Transcripts.
🔗 authors.elsevier.com/a/1lwyj3vVUP...

How does PRMT5 link splicing to mRNA export?

Out in Mol Cell: by methylating Sm proteins, PRMT5 releases mRNAs that would otherwise remain trapped on chromatin.

Meet GRIPPs: Genomically Retained Incompletely Processed Polyadenylated Transcripts.
🔗 authors.elsevier.com/a/1lwyj3vVUP...

"We added the requested experiments and thank the reviewers for their helpful suggestions"

EPIGENETIC HULK READY TO SMASH AGAIN! GET IN LOSERS!

#NIH is hanging by a thread. The #CDC has been decimated. #RFK Jr. and Russell #Vought are psychopaths--I don't say this frivolously--they are cold, calculating, inflicting violence on millions through public policy. It is where we are right now. These men are not normal. 1/

Pentagon plans military deployment in Chicago as Trump eyes crackdown President Donald Trump said Chicago is his next likely target to crack down on urban crime. Military planning has been ongoing for weeks, officials say.

We’re 7 months in, and “Pentagon plans military deployment in Chicago” is a headline in the Washington Post. And because it’s city number three, we’re already numbing to it.

If you read this about any other democracy in the world, you’d conclude that it was well on the road to a dictatorship.

Situation on 14th St and W St. NW, with federal agents -- no specific agency identified -- pulling cars over for checks. They arrested a Black woman in this car.

BIG crowd of people shouting at police.

"Fuck you!"

"What is wrong with you!"

"You don't need to terrorize people like this!"

HHS Winds Down mRNA Vaccine Development Under BARDA WASHINGTON, DC—AUGUST 5, 2025—The U.S. Department of Health and Human Services (HHS) today announced the beginning of a coordinated wind-down of its mRNA vaccine development activities under the Biomedical Advanced Research and Development Authority (BARDA), including the cancellation and de-scoping of various contracts and solicitations. The decision follows a comprehensive review of mRNA-related investments initiated during the COVID-19 public health emergency. “We reviewed the science, listened to the experts, and acted,” said HHS Secretary Robert F. Kennedy, Jr. “BARDA is terminating 22 mRNA vaccine development investments because the data show these vaccines fail to protect effectively against upper respiratory infections like COVID and flu. We’re shifting that funding toward safer, broader vaccine platforms that remain effective even as viruses mutate.”

Release from HHS: HHS will wind down its development of the mRNA vaccine development activities under the Biomedical Advanced Research and Development Authority (BARDA).

Shout out to the WSJ journalists who reported on Vought’s impoundment by footnote, causing the White House to walk it back. Impact journalism!!

PRMT5 activity sustains histone production to maintain genome integrity Histone proteins package DNA into nucleosomes, forming chromatin and thereby safeguarding genome integrity. Proper histone expression is essential for cell proliferation and chromatin organization, ye...

Why can’t cells live without PRMT5? Our new transformative work inspired and led by
@jacobroth13.bsky.social (who defends his thesis tomorrow!) shows that this arginine methyltransferase is critical for histone production and genome stability.
Full story: www.biorxiv.org/content/10.1...
1/5

PRMT5 activity sustains histone production to maintain genome integrity Histone proteins package DNA into nucleosomes, forming chromatin and thereby safeguarding genome integrity. Proper histone expression is essential for cell proliferation and chromatin organization, ye...

This feedback loop explains why PRMT5 is cell-essential: by coordinating histone supply, PRMT5 ensures proper chromatin assembly, genome integrity & cell proliferation. No PRMT5 = no histones = stalled growth. @JacobRoth13.

Check it out: doi.org/10.1101/2025.07.03.663002

5/5

Mechanistically, soluble histone H4 accumulates at histone locus bodies upon PRMT5 inhibition, and H4 R3 mutants localize more robustly than WT—supporting methylation-driven feedback at histone loci.
4/5

Inhibiting or knocking down PRMT5 triggers rapid histone mRNA depletion, histone protein loss & replication-associated nuclear abnormalities (micronuclei, γH2AX foci), directly linking arginine methylation to genome stability.
3/5

Using time-resolved nascent transcription profiling, quantitative proteomics & imaging, we show that PRMT5 is required to sustain histone mRNA transcription & histone protein synthesis during S-phase—when demand for new histones peaks.
2/5

PRMT5 activity sustains histone production to maintain genome integrity Histone proteins package DNA into nucleosomes, forming chromatin and thereby safeguarding genome integrity. Proper histone expression is essential for cell proliferation and chromatin organization, ye...

Why can’t cells live without PRMT5? Our new transformative work inspired and led by
@jacobroth13.bsky.social (who defends his thesis tomorrow!) shows that this arginine methyltransferase is critical for histone production and genome stability.
Full story: www.biorxiv.org/content/10.1...
1/5

World’s premier cancer institute faces crippling cuts and chaos | CNN The Trump administration’s broadsides against scientific research have caused unprecedented upheaval at the National Cancer Institute, the storied federal government research hub that has spearheaded ...

New hair-raising piece from CNN about the National Cancer Institute...

www.cnn.com/2025/07/08/h...

Powerful statement by Sen. Alex Padilla.

Please notice that anytime senators or representatives try to conduct oversight, they’re blocked.

In this case, a sitting US senator was tackled to the ground and handcuffed—for asking a question.

Where the hell has Chuck Schumer been on this?

For all my NYC Chromatin / Epigenetics / Gene Expression colleagues - the registration and abstract deadline for our Summer '25 symposium is this Friday. Attendance is free (lunch and coffee breaks provided), but we need you to sign up! See here: mailchi.mp/cbee4a4e6267...

Excited for this summer’s NYC Chromatin Club!

Grad students & postdocs: submit your abstracts for a chance to present a poster or talk. Come connect w/ fellow epigenetic New Yorkers!

#NYCChromatinClub
@dshechter.bsky.social @vivrisca.bsky.social @epicypher.bsky.social
@kjarmache.bsky.social

TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia https://www.biorxiv.org/content/10.1101/2025.04.07.647605v1

TTLL4 glutamyltransferase is a therapeutic target for NPM1-mutated acute myeloid leukemia https://www.biorxiv.org/content/10.1101/2025.04.07.647605v1

That foundation of basic science, funded by the NIH and DoD/CDMRP, led us here: to a druggable AML vulnerability.
Basic science matters. So does federal funding. /end

This story began with our curiosity-driven work in Xenopus frogs and proteins—studying glutamate-glutamylation in basic chromatin biology of histone chaperone function. bit.ly/4j7uEnB and and go.nature.com/42GgDXW and bit.ly/3XVCrMJ /7

TTLL4 is a post-translational regulator of leukemia maintenance.
It’s druggable. It’s specific. And it’s a promising new angle in a challenging AML subtype.
This is exactly the kind of science made possible by federal funding. /6

We didn’t stop there:
Through biochemical and virtual screening, we identified TTLL4 inhibitors.
One compound, EN7, selectively impairs NPM1c AML cells—while sparing wildtype cells. /5

In a Npm1c;NrasG12D/+ mouse model, Ttll4 deletion reduced leukemia burden and significantly prolonged survival. /4

TTLL4 adds a glutamyl group to NPM1 at E126.
Without it, NPM1c shifts back to the nucleus—disrupting its ability to sustain leukemia.
Loss of TTLL4 phenocopies NPM1c degradation:
Lower proliferation, more myeloid differentiation, and broad gene expression changes. /3