Andrew Wells

Congrats Gerd, well-deserved!

Congratulations to the 3 @pennmedicine.bsky.social honorees elected to the National Academy of Medicine! Election to @nam.edu is considered one of the highest honors in the field of health & medicine. Check back this week as we profile each new member tinyurl.com/ysjzdrbk

Large-scale multiomic analysis identifies non-coding somatic driver mutations and nominates ZFP36L2 as a driver gene for pancreatic ductal adenocarcinoma Background The identification and characterisation of somatic cancer driver mutations in the non-coding genome remains challenging. Objective To broadly characterise non-coding driver mutations for p...

Congratulations to the @amundadottir.bsky.social team for their #Gut paper reporting a large-scale multiomic analysis of pancreatic ductal adenocarcinoma. Delighted to contribute along with @adwellspenn.bsky.social. @chopresearch.bsky.social @penngenetics.bsky.social

gut.bmj.com/content/earl...

My husband was detained by ICE today

Juan Muñoz, an American citizen, father of 2, and local government official, was peacefully protesting w. other elected officials. He was assaulted and taken away

I have had zero contact or updates since

#SOS
@duckworth.senate.gov @durbin.senate.gov

A little thread: Science is defiantly anti-fascist because it pursues truth, is necessarily collaborative, and relies on open communication. And because its falsifiability is incompatible with the cultism, faith-based belief systems, disinformation, and propaganda of Christian nationalism.

GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density - Genome Biology Background Over 1100 independent signals have been identified with genome-wide association studies (GWAS) for bone mineral density (BMD), a key risk factor for mortality-increasing fragility fractures; however, the effector gene(s) for most remain unknown. Results We execute a CRISPRi screen in human fetal osteoblasts (hFOBs) with single-cell RNA-seq read-out for 89 non-coding elements predicted to regulate osteoblast gene expression at BMD GWAS loci. The BMD relevance of hFOBs is supported by heritability enrichment from stratified LD-score regression involving 98 cell types grouped into 15 tissues. Twenty-three genes show perturbation in the screen, with four (ARID5B, CC2D1B, EIF4G2, and NCOA3) exhibiting consistent effects upon siRNA knockdown on three measures of osteoblast maturation and mineralization. Lastly, additional heritability enrichments, genetic correlations, and multi-trait fine-mapping unexpectedly reveal that many BMD GWAS signals are pleiotropic and likely mediate their effects via non-bone tissues. Conclusions Our results provide a roadmap for how single-cell CRISPRi screens may be applied to the challenging task of resolving effector gene identities at all BMD GWAS loci. Extending our CRISPRi screening approach to other tissues could play a key role in fully elucidating the etiology of BMD.

Our latest paper, just out in #GenomeBiology: "GWAS-informed data integration and non-coding CRISPRi screen illuminate genetic etiology of bone mineral density". @chopresearch.bsky.social @penngenetics.bsky.social
genomebiology.biomedcentral.com/articles/10....

Super excited to share my final postdoc paper from Rabinowitz lab- on how whole-body and tissue metabolism changes in viral infection!
pubmed.ncbi.nlm.nih.gov/40581045/

Here's the NIH's proposed budget - from $48 billion to $27 billion. NIAID, current ~$7 billion cut to ~$4.2 billion.

The proposed 15% cap on indirect costs remains.

Again, these budgets are passed, and our leadership in science, technology, and innovation is gone.

www.hhs.gov/sites/defaul...

NSF, NASA and NIH budgets per year, inflation adjusted from 2000-2025 along with the proposed cuts. NSF includes research component only. Massive cuts across all sectors, well below support spanning 25 years.

How bad will it be? Catastrophic.

Proposed cuts to #NSF, #NIH, and #NASA will set the US R&D landscape back 25 yrs+, cause economic and job loss now, and undermine innovations to come.

But, this is the WH's *proposed* budget.

Speak up now before it is too late.

(inflation adjusted $-s below)

“Maybe we need to treat more diabetes with cooking classes, not just throwing insulin at people,” FDA Commissioner Marty Makary said on Fox News’ Sunday Futures. “You know, scientists have been waving the flag for years, saying you’ve got to look at this body of scientific data, and the modern medical establishment really has been disconnected.”

As the parent of a type-I diabetic, I would like to invite the ignorant piece of shit currently directing the FDA to kiss my ass.

To my fellow colleagues at institutions denied federal funding by the current administration, will you serve on NIH study section panels when requested??

Trump Has Cut Science Funding to Its Lowest Level in Decades (Gift Article) The lag in funding extends far beyond D.E.I. initiatives, affecting almost every area of science: chemistry, computing, engineering, materials and more.

The @upshot.nytimes.com has put together a vivid illustration of how the Trump administration has hollowed out American science. Gift link: nyti.ms/4kBTVql

🚨 A new rule would let career scientists like NSF/NIH program officers be replaced by political appointees

Already 14,000+ public comments, deadline is Friday

📣 Comments can be short. Courts consider them—and scientists with NSF/NIH experience are especially impactful

Speak up! shorturl.at/WKuBj

All of NIH funding to Northwestern University is frozen. This pause includes noncompeting approved funding, new and competing grants with fundable scores. No reimbursements for money already spent have been received since March. This situation is rarely reported so please Please get the word out!

NIH Budget (2025 Dollars) Presidential Proposal -- Congressional Appropriation FY2026 Presidential Proposal Fiscal Year

Check this chart.
Purple line: NIH actual budget (as passed by Congress) after 2000.
This is in real (inflation-adjusted) dollars.

The Trump/Vought proposal for 2026 (yellow) is catastrophic, for US science and medical cures for Americans. That's a massive drop.

The Babadoo

Trump proposes unprecedented budget cuts to US science Huge reductions, if enacted, could have ‘catastrophic’ effects on US competitiveness and the scientific pipeline, critics say.

This would decimate academic science

www.nature.com/articles/d41...

Characterization of non-coding variants associated with transcription-factor binding through ATAC-seq-defined footprint QTLs in liver Dudek et al. use chromatin accessibility data in liver from 170 human donors to measure transcription factor binding at genetic variants. They observed 809 variants associated with binding. Given bind...

@maxdudek.bsky.social applied a deep learning algorithm to ATAC-seq from 170 livers to measure TF binding at non-coding variants. We show "footprint QTLs" (#fpQTLs) can fine-map causal variants. @ajhgnews.bsky.social @penngenetics.bsky.social @chopresearch.bsky.social
www.cell.com/ajhg/abstrac...

Characterization of non-coding variants associated with transcription-factor binding through ATAC-seq-defined footprint QTLs in liver Dudek et al. use chromatin accessibility data in liver from 170 human donors to measure transcription factor binding at genetic variants. They observed 809 variants associated with binding. Given bind...

Our new paper is out today in AJHG! We applied a "footprinting" algorithm to ATAC-seq data from 170 livers to find non-coding variants associated with TF binding. We show that these "footprint QTLs" (#fpQTLs) can fine-map GWAS loci at base-pair resolution.
www.cell.com/ajhg/fulltex...

Internal budget document reveals extent of Trump’s proposed health cuts HHS would be asked to absorb a $40 billion cut, about one third of its discretionary budget.

SCOOP: Internal budget doc reveals extent of Trump’s proposed health cuts. About 1/3 of HHS discretionary budget. Our story w @carolynyjohnson.bsky.social @rachelroubein.bsky.social @joelachenbach.bsky.social @laurenweberhp.bsky.social www.washingtonpost.com/health/2025/...

Five things to know if your federal grant is terminated If you want to appeal the decision, know the rules that govern terminations, as well as the specific rationale given in your notice, science policy experts say.

www.thetransmitter.org/funding/five...

Images of protests and crowds across the country. HANDSOFF APRIL 5TH 2025 BOSTON NEW YORK CHICAGO PORTLAND SAN FRANCISCO SAN DIEGO IDAHO UTAH OAKLAND (AND SOOOO MANY MORE!)

They are now estimating 2.3 million across the country. Keep it going folks.

#handsoff #50501protests

Another Child Dies from Measles RFK Jr. plans to attend the funeral. He should apologize to the parents for his actions during a measles epidemic that likely involves thousands of children.

open.substack.com/pub/pauloffi...
RFK Jr. should apologize to parents for his inaction during this measles epidemic.

NIH Grants Fueled $95 Billion In FY 2024 Economic Activity, Finds New Report National Institutes of Health grants generated almost $95 billion in economic activity nationwide in FY 2024 according to a new report by United for Medical Research.

New report shows that NIH grants fueled $95 billion in economic activity and 407,782 jobs in 2024.

That's not to mention the countless lives that biomedical research has saved.

Show me a better investment than that.
www.forbes.com/sites/michae...

I am somehow for the first time ever reviewing for PNAS and their reviewer instructions include this BANGER of a line:

"The purpose of peer review is not to demonstrate proficiency in identifying flaws"

Print it in eleventy point font and hang it from the hillside. Scream it from the rooftops.

Currently there are many more children with measles (a disease that was thought eradicated in 2000) in this country than trans athletes

Trump credit card freeze sparks alarm at health agencies “Cost efficiency” order could block travel, supplies for labs and patient care

A new White House freeze on using government-issued credit cards is the latest shock for federal scientists, potentially affecting everything from conference travel to needed purchases for clinical care or lab work. scim.ag/4hV9oRb

Trump Places Freeze On Federal Credit Cards In Newest DOGE Executive Order The order gives the Department of Government Efficiency more power over federal funds and spending practices.

This is a straight ban on purchasing at #NIH — for cancer trials, treating patients, and developing cures. @chrislhayes.bsky.social

Almost all purchases at NIH are made on govt credit cards.

It’s clear what’s happening: Trump/Musk are blowing up the govt using devious… 1/
www.forbes.com/sites...

UPDATE ON FUNDING

These are data through 2/21/25. The lag in Reporter really does appear to be about a week.

There was a second mini-pause as suspected from internal reports, but grants are being awarded.

About 21% new or competitive renewals (compared to 29% in 2017, and 22% in 2021