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Hiten Madhani

@hitenmadhani.bsky.social

Gene regulation in health and disease | Professor/Vice-Chair @UCSF Dept. of Biochemistry and Biophysic | via Stanford, UCSF and MIT | https://madhanilab.ucsf.edu

5,216 Followers  |  5,497 Following  |  438 Posts  |  Joined: 18.08.2023
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Posts by Hiten Madhani (@hitenmadhani.bsky.social)

Flyer for symposium: https://ctrlepiedit.sciencesconf.org/

Flyer for symposium: https://ctrlepiedit.sciencesconf.org/

Very excited to announce the FIRST symposium on epigenome editing! These tools are becoming widely used in mol bio, ag & therapy. It's time to bring leaders together to discuss this rapidly growing and exciting field. And why not in Paris! Please register & share! (1/2) ctrlepiedit.sciencesconf.org

09.03.2026 13:15 β€” πŸ‘ 59    πŸ” 35    πŸ’¬ 3    πŸ“Œ 5
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a cartoon says hey everybody an old man 's talking while bart simpson looks on ALT: a cartoon says hey everybody an old man 's talking while bart simpson looks on

A short Bluetorial on plots of NIH application success rates as a function of percentile.

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09.03.2026 14:56 β€” πŸ‘ 102    πŸ” 47    πŸ’¬ 1    πŸ“Œ 2
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Nice day for a stroll!

07.03.2026 18:15 β€” πŸ‘ 6    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

Current NIH leadership want you to think they are using rigorous, consistent & scientific processes to screen studies to align them with agency priorities.

But the process that they have put down on paper is a sham.

It’s important to know NIH is not following its own guidance. Here’s why:

🧡1/

06.03.2026 14:35 β€” πŸ‘ 197    πŸ” 125    πŸ’¬ 4    πŸ“Œ 10
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Self-clustering of three CBX2 molecules drives PRC2 to promote facultative heterochromatinization of Polycomb target genes Ingersoll et al. uncover that approximately three CBX2 molecules drive PRC2 clustering and H3K27me3 deposition in mESCs. This process supports a model in which few CBX2 molecules self-cluster on chrom...

Nice work in Mol. Cell that mirrors our work in Cryptococcus neoformans from a few years back (authors are seemingly not aware of it) : www.nature.com/articles/s41...

www.cell.com/molecular-ce...

05.03.2026 20:18 β€” πŸ‘ 9    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
A photo of Doc Brown from Back to the Future holding jumper cables labelled "Deranged Activist" with a grant of NIH funding curves below it.

A photo of Doc Brown from Back to the Future holding jumper cables labelled "Deranged Activist" with a grant of NIH funding curves below it.

My weekly update on NIH funding

This includes awards made through 2/27/26

Warning: This thread contains data compiled by a known deranged_activistβ„’. Do not read while operating heavy machinery.

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05.03.2026 16:38 β€” πŸ‘ 101    πŸ” 38    πŸ’¬ 2    πŸ“Œ 7
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Sequence-specific RNA recognition drives Restrictor-mediated termination of extragenic transcription Polizzese et al. show that the C3H1 zinc fingers (ZNFs) of ZC3H4 confer sequence-specific RNA binding to Restrictor. These ZNFs recognize a degenerate A/UGUA motif at ncRNA 5β€² ends and are required fo...

A remarkably similar motif was found in this paper to the motif (UGUA) for Nrd1-dependent termination of cryptic unstable transcripts in S. cerevisiae, but with a completely different RNA-binding protein. Convergent evolution or re-wiring?

www.cell.com/molecular-ce...

03.03.2026 16:43 β€” πŸ‘ 6    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0

Some shit is about to go down with NIH study sections, friends. Keep your eyes peeled for change that may affect your grant submissions.

03.03.2026 02:30 β€” πŸ‘ 80    πŸ” 39    πŸ’¬ 7    πŸ“Œ 7
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White House stalls release of approved US science budgets The US Congress rejected sweeping cuts to science agencies. But the NIH, the NSF and NASA have had their spending slowed.

Congress rejected massive cuts to US science budgets for 2026, but much of the money still isn’t flowing to researchers.

The culprit? The White House Office of Management and Budget (OMB) is quietly slow-walking the release of funds. πŸ§΅πŸ‘‡

27.02.2026 16:06 β€” πŸ‘ 1054    πŸ” 711    πŸ’¬ 20    πŸ“Œ 75

If you want a science cleanse today, read and celebrate the accomplishments of these amazing young scientists

26.02.2026 21:32 β€” πŸ‘ 29    πŸ” 9    πŸ’¬ 0    πŸ“Œ 0

Great stuff! Fun factβ€”my baymate in grad school, Anne de Bruyn Kops, isolated the original brr6-1 mutation in a nuclear export, cloned it, and stayed on to work on it. Same cs library that Suzanne Noble cloned the splicing factors Brr1and Brr2 out of via a Northern blot/Primer-extension screen!

25.02.2026 18:23 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0
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Voices: Medical research saved my daughter’s life. We must protect the funding that makes that research possible. β€œScientists are seeking new treatments and cures for many diseases, common and rare,” writes Lateishia Curtis in an op-ed. β€œTalk to friends, neighbors and policymakers about medical research. The next...

Wonderful op-ed by a mother who explains how NIH-funded research at U of U Health saved her daughter's life.

"That research β€” and Briar’s life β€” demonstrate just how critical federal support is to scientists, doctors and, especially, the patients they help."
www.sltrib.com/opinion/comm...

17.02.2026 22:30 β€” πŸ‘ 63    πŸ” 35    πŸ’¬ 0    πŸ“Œ 2

Would add to this thorough list of harms at NIH:

1) multiyear funding, Vought’s trick to fund less new research with the same amount of $

2) presidentializing of NIH, shifting toward a political agenda rather than science. More on that from @markhisted.org: open.substack.com/pub/donmoyni...

18.02.2026 05:53 β€” πŸ‘ 50    πŸ” 16    πŸ’¬ 1    πŸ“Œ 0
Dear Director Bhattacharya and Deputy Director Lorsch: I saw a post Director Bhattacharya retweeted about replication in economics. This begins with:

Between 1974 and 2014, only 0.1% of publications in the top 50 economics journals were replication studies.
That's 40 years. Thousands of papers. Almost none replicated.
We've built careers on findings no one has verified.
When economists finally replicate studies, 40-67% fail depending on the study.

Dear Director Bhattacharya and Deputy Director Lorsch: I saw a post Director Bhattacharya retweeted about replication in economics. This begins with: Between 1974 and 2014, only 0.1% of publications in the top 50 economics journals were replication studies. That's 40 years. Thousands of papers. Almost none replicated. We've built careers on findings no one has verified. When economists finally replicate studies, 40-67% fail depending on the study.

A second email, this with a more substantial insight about "The Replication Crisis"...

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21.02.2026 17:12 β€” πŸ‘ 74    πŸ” 27    πŸ’¬ 6    πŸ“Œ 4

Thank your NIH POs: they are working under challenging dictates, including being required to multi-year fund (and therefore cut) grants. Congress caving on MYF means that the NIH budget has been effectively cut significantly. There’s no sugar-coating this.

21.02.2026 15:39 β€” πŸ‘ 10    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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UCSD, facing federal cuts, will no longer guarantee funding for incoming grad students The school warns admitted first-year students that their support packages are contingent on state and federal funding.

It’s PhD admission season in the US and elsewhere. Is anyone collecting and sharing info about what admissions letters are saying this year, especially in the neuro/psych/bio space? Last year there were some (unfortunate) changes at some Unis, eg
www.sandiegouniontribune.com/2025/03/08/u....

21.02.2026 09:51 β€” πŸ‘ 40    πŸ” 27    πŸ’¬ 3    πŸ“Œ 1
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a cartoon of stitch covering his eyes with his hands and the words uggg !! below him . ALT: a cartoon of stitch covering his eyes with his hands and the words uggg !! below him .

One of my pet peeves is people calling proteins "metazoan-specific splicing factors" just because they aren't found in S. cerevisiae. Please take a look at this paper from @hitenmadhani.bsky.social and Scott Roy!

pubmed.ncbi.nlm.nih.gov/34555349/

18.02.2026 16:48 β€” πŸ‘ 7    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0

The first centromeres to be cloned (by chromosome walking) by Clarke and Carbon (should have won them a Nobel) were mysterious in their origin. Max et al have solved the mystery.

18.02.2026 16:19 β€” πŸ‘ 17    πŸ” 2    πŸ’¬ 1    πŸ“Œ 1

*complexity

18.02.2026 15:00 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

I argued in a piece I wrote in 2013 called β€˜the frustrated gene’ that caps are an antiviral defense. Hence some viruses steal caps, other have their own capping enzymes, while others evolved IRESs. Here’s a virus that captured the entire cap recognition machinery. Conflicts begets comlexity.

18.02.2026 07:08 β€” πŸ‘ 21    πŸ” 7    πŸ’¬ 3    πŸ“Œ 0
A line graph shown the number of NIH new and competitive awards funded for fiscal year 2026 (through 2/13/26) compared with fiscal years 2021-2025. The fiscal year 2026 is lagging well behind with only 569 awards made through 2/13/26 compared to >2000 for previous fiscal years.

A line graph shown the number of NIH new and competitive awards funded for fiscal year 2026 (through 2/13/26) compared with fiscal years 2021-2025. The fiscal year 2026 is lagging well behind with only 569 awards made through 2/13/26 compared to >2000 for previous fiscal years.

New and competitive renewal awards.

The number of awards is 569 compared with more than 2200 through the same date in earlier fiscal years.

All ICs have now made awards except for NIAAA, NCCIH, NLM, FIC, and OD. NEI (Eye Institute) made its first award during the new period.

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17.02.2026 16:55 β€” πŸ‘ 32    πŸ” 43    πŸ’¬ 6    πŸ“Œ 6

I would ask people to call or message their senators about this and specifically that Vinay Prasad needs to be out at FDA. Even the Wall Street Journal has said as much. There is push back. Companies won’t fund clinical trials if they can’t trust the FDA.

13.02.2026 01:52 β€” πŸ‘ 89    πŸ” 46    πŸ’¬ 0    πŸ“Œ 1

NIH, CDC, HHS, and all of US cancer research and public health needed and still needs protection from Russell Vought and the P2025 White House.

The defining feature of 2025 at NIH was not merely grant changes.
It was unprecedented levels of presidential interference with NIH decision-making.
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12.02.2026 22:58 β€” πŸ‘ 109    πŸ” 64    πŸ’¬ 2    πŸ“Œ 2
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Opinion | I Just Returned From China. We Are Not Winning.

β€œFor starters, we need to reverse the cuts that Mr. Trump has made to investments in science and other areas. β€œ

I Just Returned From China. We Are Not Winning. www.nytimes.com/2026/02/10/o...

11.02.2026 05:39 β€” πŸ‘ 3    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0

I don’t understand. If a R01 funding period is over, how does MYF help? Would NCE be the dilution? Or are you saying carry over from another grant would be allowed depending on whether the type 4 award allows it? My understanding is that some type 4 awards allow flexibility but others don’t.

08.02.2026 19:06 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0
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Nice day for a pre-Super Bowl stroll!

07.02.2026 19:55 β€” πŸ‘ 4    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

The original language was to limit MYF to 2023 levels. Last fiscal year it was used to β€˜use up’ the budget so that many fewer awards happened. Same will be true the next yr. Either they will trim awards, shrink new award amounts, or award fewer grants. Meanwhile 70B increase for DHS.

07.02.2026 05:21 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

But the impact of MYF will make paylines crater nonetheless.

07.02.2026 00:38 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 2    πŸ“Œ 0
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A non-catalytic role for RFC in PCNA-mediated processive DNA synthesis The RFC clamp loader remains associated with PCNA beyond the loading step, supporting processive DNA replication by stabilizing the inherently unstable PCNA-polymerase ẟ complex.

Nice to see some yeast genetics in a Cell paper, where the authors test models based on single-molecule in vitro analysis. The combination of genetics and biochemistry often addresses questions most effectively.
www.cell.com/cell/fulltex...

06.02.2026 18:06 β€” πŸ‘ 20    πŸ” 7    πŸ’¬ 0    πŸ“Œ 0

Meanwhile in China…

06.02.2026 07:04 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0