iiinova — where your digital self keeps evolving

Chad Weldy, MD, PhD @chadweldy.bsky.social · 20/04/2026

I am thrilled to say that I have accepted a position as Assistant Prof at @stanforduniversity.bsky.social CV Medicine and am launching the Weldy Lab at Stanford! My work integrates genetics, epigenetics, RNA biology, and cardiovascular disease. Check it out: weldylab.org Recruiting!

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Reposted by Chad Weldy, MD, PhD

Jeremy Berg @jeremymberg.bsky.social · 01/03/2026

NSF Update (Awards through 2/27/26) Directorates to follow 1/10

A line graph showing NSF grant awards made through 2/27/26 for fiscal year 2026 compared with grant awards for fiscal years 2021-2025.

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 26/02/2026

Great to see our review on ADAR1 and dsRNA sensing out in ATVB @ahascience.bsky.social today! Our understanding of the ADAR1-dsRNA-MDA5 axis in complex and rare disease is changing rapidly with important implications for therapy --> worth a read. #RNAsky www.ahajournals.org/doi/10.1161/...

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Reposted by Chad Weldy, MD, PhD

Jenna Norton @jenna-m-norton.bsky.social · 20/02/2026

Check this out straight from the NIH website, acknowledging that multiyear funding was likely responsible for a 20% decrease in early stage investigators. And that it was expected. A strange approach for someone so committed to the next generation of scientists. grants.nih.gov/news-events/...

Screenshot from an NIH website reading: "Table 1 shows the number of principal investigators (PIs) applying for or receiving an R01-equivalent grant in FYs 2021 to 2025, disaggregated by career stage. NIH supported 1,423 and 1,144 ESIs in FYs 2024 and 2025, respectively. The decrease seen in FY 2025 may likely be due in part to NIH implementing a requirement to use 50% of its remaining competing Research Project Grant (RPG) funds (starting in June 2025) for full-year funded competing RPGs, which was expected to lead to fewer awards and support fewer researchers overall."

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Reposted by Chad Weldy, MD, PhD

Qianru Wang @qianru.bsky.social · 30/01/2026

Thrilled that @stanfordmedicine.bsky.social Comms highlighted our work on epistasis in their Insights channel! 🧬💛🌟 Grateful to work with an incredible team: my postdoc advisor @euanashley.bsky.social, co-corresponding author Bin Yu, and co–first author Tiffany Tang. med.stanford.edu/news/insight...

med.stanford.edu

Behind the Science: Epistasis, the sly genetic tag team behind some heart disease

Euan Ashley’s lab uncovers the workings of epistasis, a type of interaction between gene variants, that could possibly transform our understanding of inherited heart diseases and much more.

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Reposted by Chad Weldy, MD, PhD

Jeremy Berg @jeremymberg.bsky.social · 27/12/2025

A relatively random thread about the degrees of NIH Directors. Not surprisingly, almost all NIH Directors have been straight MD holders. However, there have been two MD-PhD holders (actually one PhD, MD and one MD, PhD, but no combined MD-PhD holders) 1/13

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 15/10/2025

Super excited we made the cover of @natcardiovascres.nature.com! Work represents ADAR1 RNA editing within the vascular wall

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Reposted by Chad Weldy, MD, PhD

Jesse Engreitz @jengreitz.bsky.social · 18/09/2025

Excited for a major milestone in our efforts to map enhancers and interpret variants in the human genome: The E2G Portal! e2g.stanford.edu This collates our predictions of enhancer-gene regulatory interactions across >1,600 cell types and tissues. Uses cases 👇 1/

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 17/09/2025

Hey thanks! Hope you’re doing well!

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

There's a lot here and a lot more in the paper. But I get excited thinking about the potential. From rare to complex disease to novel mechanisms with real potential for a precision guided approach to therapy. A lot to do! @stanfordmedicine.bsky.social @stanforddeptmed.bsky.social

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

To then connect this back to humans, entirely grateful for collaborators @clintomics.bsky.social & Sander van der Laan where we investigated ISG activation and SMC modulation and plaque phenotype in the Athero-Express cohort, showing distinct relationships between ISG induction and calcification

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

Importantly, we define the cellular trajectory of MDA5 activation leading to vascular calcification and disease progression, an effect that can be entirely inhibited with simply haploinsufficiency of MDA5.

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

This MDA5 activation leads to increased plaque size due to increased SMC migration into the plaque with markedly increased vascular calcification.

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

But importantly, we show that with SMC ADAR1 haploinsufficiency, atherosclerosis studies reveal that MDA5 activation occurs in a cell type and context specific mechanism. MDA5 activation drives a distinct SMC cell state change.

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

In atherosclerosis - we show that SMCs appear to be enriched for these immunogenic RNA, and that as SMC undergo phenotypic modulation in both human and mouse there is significant activation of ISG genes, potentially suggestive of MDA5 activation

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

With homozygous deletion of ADAR1 in SMC, there is a loss of vascular integrity. Further single cell RNA sequencing reveals distinct ISG activation and cellular infiltration with critical receptor ligand interaction

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

Our work here gets at this mechanism. We reveal a fundamental observation, that vascular SMC have a unique requirement for ADAR1 editing to prevent MDA5 activation. SMC deletion of ADAR1 leads to severe phenotype within days and is entirely blocked with deletion of MDA5

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

In addition, rare LOF variants in MDA5 (IFIH1) have been found to be protective against CAD as well as other inflammatory disorders. This provides quite strong human genetic evidence to support ADAR1-dsRNA-MDA5 axis in CAD, but through what mechanism?

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

The big finding in 2022 by my colleagues Qin Li (now @upenn.edu and Billy Li @stanforduniversity.bsky.social) was that beyond rare disease, common variants appear to regulate RNA editing (edQTLs), and these edQTLs predict numerous common inflammatory disorders, including CAD! t.co/t1i47lPlGG

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

Amazingly, mice that are deficient in ADAR1 are embryonic lethal, but dual knock out of ADAR1 and MDA5 essentially rescues the phenotype. In this case, the role of ADAR1 seems to be nearly entirely based on preventing MDA5 activation, less so the actual edit of the transcript

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

In rare disease, loss of ADAR1 causes a severe interferonopathy due to the build up of dsRNA and activation of the dsRNA receptor MDA5 (gene symbol IFIH1). Similarly, gain of function variants in MDA5 (IFIH1) cause the same disorders, including severe vascular calcification

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

RNA has the peculiar pattern of having long repetitive elements on either end, where these strands fold over on each other to make double strand RNA structures -> turns out this looks a lot like a dsRNA virus! So why doesn't this dsRNA induce an antiviral response? ADAR1!

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

When ADAR editing occurs in the coding region of a transcript, it serves as an A -> G edit and can change protein function. Even in coral and octopus in response to temperature changes of the ocean, whoa! Although amazingly, the majority of editing sites are non-coding (hmm)

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 16/09/2025

What is RNA editing and how does this relate to coronary artery disease?? There's a lot here but it's fascinating. A to I editing is an under appreciated area of biology, where ADAR enzymes deaminate adenosine to inosine. Thousands of RNA molecules are edited all the time!

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

This work is exciting in that it defines an important area of vascular biology with key relevance to understanding genetic drivers of disease risk, couldn't have been done with out the amazing support of Tom Quertermous and all our amazing collaborators and team @stanfordmedicine.bsky.social

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Through ChromBPNet analysis, by identifying the variants that affect chromatin accessibility in a vascular site specific manner, we identified that many of these variants land in key developmental TF motifs such as MEF2A, HAND2, as well as other regulatory TFs important in disease risk such as SMAD3

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Not only can we reveal and predict variant effect on chromatin accessibility, but we define that effect varies by vascular site even within cell type

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

But how does this relate to human disease?? Through an awesome collaboration with the @anshulkundaje.bsky.social lab, we trained ChromBPNet models with scATACseq datasets for each cell type and vascular site, and predict human variant effect on a cell type/site basis @soumyakundu.bsky.social

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Gene regulatory network analysis through integrated RNA and ATAC datasets across cell types and vascular sites reveal cell type and vascular site specific GRNs, this highlighted ascending fibroblast specific MEOX1

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Vascular site specific epigenomic patterns are distinct for SMCs, fibroblasts, as well as endothelial cells, but importantly not macrophage cells. While developmental TFs a enriched there are thousands of distinct enhancer elements across vascular sites

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Many enhancers correspond to developmental origin and highlight specific developmental transcription factors such as HAND2, GATA4, and HOX family members, suggestive of an epigenetic 'memory' of developmental origin

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

In our work, by performing single cell RNA and ATAC sequencing across different vascular sites in mice, we reveal that the epigenomic landscape is distinct to not only cell type, but vascular site, defining vascular site specific enhancers

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

A critical element of complex genetics is that the majority of GWAS SNPs that influence disease regulate non-coding enhancer elements in the genome — where variants can influence disease risk through regulating cell type specific enhancers, but what about for the vasculature??

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

However we know that the genetic drivers of complex vascular traits vary based on vascular site, a beautiful example is the exceptional work by @jamespirruccello.com in 2022 showing the different genetic variants that impact ascending versus descending aortic dimension

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

Beautiful work in developmental biology going back decades has revealed that vascular diversity has a developmental basis, and that these vascular territories have distinct biology

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Chad Weldy, MD, PhD @chadweldy.bsky.social · 10/09/2025

A fascinating observation going back nearly 60 years is that different vascular territories have distinct susceptibility to disease, and vascular disease is uniquely site specific, but why??

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Reposted by Chad Weldy, MD, PhD

Carmen Guerra, MD, MSCE @guerraviswanath.bsky.social · 29/06/2025

www.cbsnews.com/video/saving.... This video shows the real and devastating impact of the cuts to the NIH funding. My heart aches from hearing the story of Natalie Phelps who has stage 4 colorectal cancer and how she and her family are being impacted.

cbsnews.com

Saving money vs. saving lives

Scientists conducting medical research are facing an existential crisis: Layoffs and budget cuts pushed by President Trump that, they say, jeopardize finding a cure for cancer. They tell "Sunday Morni...

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Reposted by Chad Weldy, MD, PhD

James Priest @jamesrpriestmd.bsky.social · 19/07/2025

This is the stupidity of it all—carve outs for AK make no sense for the people of Alaska when the UW/Harborview/Seattle Children’s system is the referral destination for anything too complicated for Anchorage

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Reposted by Chad Weldy, MD, PhD

Carl Zimmer @carlzimmer.com · 26/06/2025

National Science Foundation staff were notified that their office space will be taken over by Department of Housing and Urban Development. It's unclear where the 1,800+ NSF employees will work. Renovation plans apparently include a personal gym for the HUD secretary & family eos.org/research-and...

eos.org

National Science Foundation Staff Booted From Headquarters - Eos

Staff at the National Science Foundation (NSF) were notified on 25 June that the agency’s office space, located in Alexandria, Va., will be taken over by Department of Housing and Urban Development (H...

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Reposted by Chad Weldy, MD, PhD

euanashley @euanashley.bsky.social · 14/06/2025

Atul Butte died yesterday. The world lost a giant. A big bear of a man. With a huge smile. With love for everyone. With energy that could power a room. I loved everything about Atul. I loved how he was always happy. I loved how excited he was about science and helping people.

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Reposted by Chad Weldy, MD, PhD

Jeremy Berg @jeremymberg.bsky.social · 09/06/2025

If you weren't angry enough already, here are the rates of non-competitive renewals through May. 4008 Non-competitive renewals were due to be funded in May. The total funded was 99! Some is due to terminations, but most is due to slow grant making due to DOGE review and other impediments. 1/2

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euanashley @euanashley.bsky.social · 29/05/2025

The NIH represents incredible value for the US economy and for the people of the world. We need to safeguard its future and that of our students and trainees. @rachelkeranen.bsky.social and I share our thoughts in today’s LA Times. www.latimes.com/opinion/stor...

latimes.com

Contributor: Slashing NIH research guarantees a less healthy, less wealthy America

The administration's cuts at the National Institutes of Health will obliterate billions in economic gains, America's scientific predominance and untold human lives.

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Reposted by Chad Weldy, MD, PhD

Jeremy Berg @jeremymberg.bsky.social · 23/05/2025

Senator Durbin noted that some (I believe Republican Senators) had indicated the US had been doing more than its share of biomedical research and it was time for other countries take a turn. I felt I had to interrupt to respond...

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Selin Jessa @selinjessa.com · 03/05/2025

Delighted to share our latest work deciphering the landscape of chromatin accessibility and modeling the DNA sequence syntax rules underlying gene regulation during human fetal development! www.biorxiv.org/content/10.1... Read on for more: 🧵 1/16 #GeneReg 🧬🖥️

biorxiv.org

Dissecting regulatory syntax in human development with scalable multiomics and deep learning

Transcription factors (TFs) establish cell identity during development by binding regulatory DNA in a sequence-specific manner, often promoting local chromatin accessibility, and regulating gene expre...

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Reposted by Chad Weldy, MD, PhD

Shoa Clarke @shoaclarke.bsky.social · 28/04/2025

Even as someone who has followed everything going on at the NIH very closely, this story made my heart sink. I hope Americans watch this and see the impact of shutting down science. This effects everyone.

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