Caleb Lareau

Trump Administration Puts New Chokehold on Billions in Health-Research Funding The National Institutes of Health can’t award grants to outside researchers under a new White House restriction.

The NIH can’t award ANY grants to outside researchers under new WH restriction, reports @wsj.com.

The pause came in the form of a footnote from OMB Director Vought, in a document that doles out federal funds to the NIH.

Prelude to rescissions, especially after his comments over the weekend?

CAR-engineered lymphocyte persistence is governed by a FAS ligand–FAS autoregulatory circuit Nature Cancer - Klebanoff and colleagues report that survival and persistence of CAR-T and CAR-NK cells are regulated by a FAS ligand–FAS autoregulatory circuit, showing that disabling FAS...

🚨Today, in #NatureCancer, we show that #CAR-T cells and #CAR-NK cells contain the seeds of their own self-destruction. Disruption of a FAS-L/FAS enhances CAR potency against liquid and solid cancers. rdcu.be/exjEy. @mskcancercenter.bsky.social @parkerici.bsky.social

We're excited to announce major upgrades to the HCR™ platform!

🧬 HiFi Architecture enables miRNA/siRNA detection with unmatched clarity.

🧪 RTU Dispensers now ship for DISCOVERY ULTRA, enabling scalable, low-variability workflows.

Explore the full announcement: tinyurl.com/39je4x8x

Must read! Super exciting work and innovative approach.

a blue sign says downloading virus please wait ALT: a blue sign says downloading virus please wait

Thanks to the many friends and colleagues at @astra-zeneca.bsky.social and @mskcancercenter.bsky.social for making this massive, petabyte-scale data science project happen.

Please drop @ryandhindsa.bsky.social and me any feedback on this exciting new direction!! 16/16

Gratifyingly, @kuludwig.bsky.social and colleagues showed highly similar results despite a different bioinformatics route, overall showing that this logic of finding viruses in WGS is a robust biological signal that can be exploited for EBV and other viruses! bsky.app/profile/kulu... 15/

Ultimately, our data reflect a clear pattern-- the outcomes of infections are highly heterogeneous, and for herpesviruses, the persistence of the viral genome is driven by MHC II variation. 14/

Reanalyzing ~30 EBV variants of unknown significance linked to nasopharyngeal carcinoma (NPC), we saw high allele freq. for all but 4 muts. Reasoning that circulating strains of EBV (infecting but not causing NPC), it is unlikely that these EBV SNVs contribute to carcinogenesis directly. 13/

For another fun side-quest, we asked if our reconstruction of EBV contained useful information about the genetic diversity of the virus itself. The logic being-- maybe it's the viral strain that is responsible for the heterogenous phenotypic consequences of infection? 12/

Borrowing from the immunotherapy literature, we then scored each individual based on their predicted best peptide to derive a per-allele, per-person score of EBV presentation ability. This measure was strongly predictive for class II alleles and reproducible in both cohorts! 11/

HLA was by far and away the strongest association, so we sought to dig in deeper. In our GWAS, we had the distinct advantage of knowing what peptides were presented on class I&II (i.e., the EBV proteome)--we scored all participants for predicted EBV peptide presentation strength via NetMHCpan. 10/

Overall, this genetic architecture of EBV DNAemia covaried with various autoimmune conditions, including SLE & RA (known EBV-linked conditions) with an opposite effect for IBD. This demonstrates that GWAS signal for these autoimmune traits is pleiotropic with EBV DNAemia. 9/

Next, we used EBV DNAemia as an outcome in a GWAS, identifying 20+ independent loci near many notable immune-associated genes such as HLA, CTLA4, EOMES, etc. The effects were strongly concordant between UKB and All of Us, a replication cohort. 8/

With EBV DNAemia as a biomarker, we then performed a phenome-wide association study, looking to identify what complex traits are linked to persistence of the viral infection. Many known and novel hits were significant, from respiratory disease to autoimmunity! 7/

By removing these regions, our measure of EBV DNAemia (i.e., persistent DNA in peripheral blood via WGS) could be derived for ~750,000 individuals. For a subset of the UKB where serology was available, our corrected measure was highly concordant only after masking these biased regions. 6/

The workflow wasn't as straightforward as we originally thought. Due to highly repetitive regions of the EBV contig, low-quality alignments gave a pervasive false-positive signal, which we were able to ultimately mitigate. 5/

In a cool twist of fate, the EBV contig is in hg38 to mop up unscrupulous EBV reads, a by-product of immortalizing lymphoblastic cell lines (used in 1000 Genomes Project, etc.). Hence, a simple `samtools view` could get a measure of persistent EBV DNA in large WGS cohorts, e.g., UK Biobank. 4/

Given the marked variation in response to a common infection, we hypothesized that a host (i.e., human) genetic variation could help explain why we have such variable responses. As we've learned from decades of GWAS, the bigger the sample size, the more one can discover, motivating our approach. 3/

Epstein Barr Virus and causes of disease

In this work, we focus on Epstein-Barr virus-- an enigma in many ways. While >90% of us have been infected by this endemic virus, most of us will live just fine. However, for a subset of the population, this infection can be a trigger of disease-- from MS to cancer to autoimmunity. 2/

the treasure trove of all sequencing datasets

Excited to share a new preprint from the lab with @ryandhindsa.bsky.social ! www.biorxiv.org/content/10.1...

Led by @sherrynyeo.bsky.social, @erinmayc.bsky.social, and friends, we continue our journey to find viral DNA in our favorite place-- the overlooked and discarded reads in existing data! 1/

AlphaFold developer Google DeepMind to fund CASP as NIH funding falls short Protein structure prediction contest CASP gets temporary funding from Google DeepMind as NIH grant runs out.

NEW from me at STAT:

We've learned that DeepMind is going to fund CASP, the protein structure competition that brought Google DeepMind's #AlphaFold to prominence (and a Nobel Prize), as its NIH funding runs out.

More @statnews.com:
www.statnews.com/2025/07/21/c...

🖥️🩺🧪🧬 #bioML

holy shit lmao

A big day for preventing mitochondrial diseases from transmitting to the next generation
www.nature.com/articles/d41...
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....

There is currently an NWS flash flood warning in effect for all five boroughs of NYC.

But no City agency has posted it on this platform.

Please help spread the word.

“If you live in a basement apartment or low-lying area, be ready to move to higher ground.”

US senators poised to reject Trump’s proposed massive science cuts Committee gives first hint that policymakers might preserve, rather than slash, funding for US National Science Foundation and other agencies.

A key US Senate committee has indicated that it will reject the huge budget cuts that President Donald Trump proposed for some science agencies, including the US National Science Foundation and NASA.

go.nature.com/40H0XST

Key numbers in cell biology

Having a sense of scale helps to think more rigorously and realistically about biological systems.

they tried to "un-woke a robot and it went full nazi" is something out of a 30 Rock TV show

Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis The transition from benign to malignant growth is a pivotal yet poorly understood step in cancer progression that marks the shift from a pathologically inert condition to a clinically lethal disease. ...

I am thrilled to share with the world a new preprint, spearheaded by the truly amazing Jose Reyes in partnership with the Lowe lab. The paper sheds light on benign to malignant transition in PDAC, uncovering roles of plasticity, tissue remodeling and P53. -> www.biorxiv.org/content/10.1...

My First Substantial Independent Research Award Was Terminated Early. Can My ESI Status Be Reinstated? June 12, 2025 Investigators lose their Early Stage Investigator (ESI) eligibility when they successfully compete for and receive a substantial independent research award. In the event an investigator’s first substantial independent research award is terminated within the first three years of the project period, and this was not due to scientific misconduct or other disqualifying events, the investigator can request the reinstatement of ESI status, using the ESI Extensions request tool in eRA commons. See Requesting an Extension for instructions. For more, see the Early Stage Investigators FAQ page.

For ESIs dealing with grants being rescinded: if an investigator’s 1st substantial independent research award is terminated within the first 3 years of the project period (not due to scientific misconduct ) they can request the reinstatement of ESI status

grants.nih.gov/news-events/...

When history marks the point where we lost the future to China, this will be it.