iiinova — where your digital self keeps evolving

Reposted by Patrick Murphy

Naba Lab UIC @nabalabuic.bsky.social · 27/04/2026

The newly redesigned #Matrisome Portal is now live: matrisome.org. Built to meet #ADA standards, the new site improves accessibility, usability, and overall experience for all. Big shout-out to Tali for leading this effort! Take a look and let us know what you think! #Accessibility #ADACompliance

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

And funding from @ahajournals.bsky.social, NIH-NHLBI and the Marlene L. Cohen and Jerome H. Fleisch Chair among other funding sources.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Very proud of the work of Sarah-Anne Nicholas, the first author and a AHA predoctoral awardee, and the excellent team of immunologists (Tony Vella, Beiyan Zhou, Maria Xu) Annabelle Rodriguez-Oquendo and members of our own lab, including Chris Pathoulas @uconnhealth.bsky.social

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Thus, endothelial Elavl1 is induced in atherogenesis and allows CD8 T cell persistence in lesions. Since CD8 T cell accumulation and activation is linked to plaque growth and rupture, and a wide range of viral responses and autoimmune conditions, Elavl1 can locally regulate these activities.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

In vitro, a novel tri-cell coculture assay (ECs + antigen presenting cells + CD8 T cells) revealed major defects in the survival of CD8 T cells and their persistence.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Pathways affected in these altered mRNA transcripts are highly enriched for the regulation of T cell interactions and mitochondrial activity. Remarkably, the deletion of Elavl1 from the endothelium nearly ablated the increase in CD8 T cells seen in carotid artery, with less effect on other cells.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Elavl1 deletion exhibited a large effect on ribosomal associated mRNA compared to total mRNA in the same system, suggesting specific effects on this translation process.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Elavl1 is enriched in the 5'UTR of transcripts at the ribosome (along with Zc3h10, which is known to regulate mRNA translation).

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Changes in mRNA at translating ribosomes (an important step to protein production) are very different for some mRNA than total mRNA levels.

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Patrick Murphy @1patrickmurphy.bsky.social · 22/04/2026

Newly published work from our lab out now #ATVB @ahajournals.bsky.social showing changes in ribosome associated mRNA in chronic conditions of disturbed flow and circulating blood lipids : www.ahajournals.org/doi/10.1161/...

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Reposted by Patrick Murphy

Harmit Singh Malik @harmitmalik.bsky.social · 16/04/2026

@hhmi-science.bsky.social's #FreemanHrabowski Scholars Program offers early career faculty up to $10M over 10 yrs, plus salary & benefits Stable, sustained support can transform your career: Senior Postdoc? This year's competition has a program for you too. Applications open 11/3! bit.ly/4vhC0LA

bit.ly

Early Career Faculty Program | Freeman Hrabowski Scholars | HHMI

The Freeman Hrabowski Scholars Program offers comprehensive support to outstanding early career faculty committed to scientific excellence in their own research, and to fostering labs that expand the ...

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Reposted by Patrick Murphy

Wayne Orr @a-wayne-orr.bsky.social · 15/04/2026

We’re hiring! Tenure-track faculty position in cancer research at LSU Health Shreveport (Pathology & Translational Pathobiology). Looking for investigators building programs at the interface of cancer, metabolism, inflammation, and vascular biology. www.lsuhsc.edu/shv/CareerOp...

lsuhsc.edu

LSUHSC Career Opportunities - Assistant/Associate/Full Professor (Tenure-Track) – Cancer Research

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Patrick Murphy @1patrickmurphy.bsky.social · 04/04/2026

Very interesting mouse model of preeclampsia - based on maternal, not fetal loss of KLF4 - where hypertension does not develop after gene deletion, but does with pregnancy: www.biorxiv.org/content/10.6...

biorxiv.org

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Patrick Murphy @1patrickmurphy.bsky.social · 25/03/2026

They are in good hands - but I can’t agree to root for the 3-peat. Let’s go Red Sox!

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Reposted by Patrick Murphy

Naba Lab UIC @nabalabuic.bsky.social · 20/03/2026

Today I would like to share a publication that is particularly meaningful to me. Our tribute to my late mentor, Richard Hynes, has just been published in Matrix Biology. I hope you will take a moment to read and celebrate the legacy of an extraordinary scientist and mentor. doi.org/10.1016/j.ma...

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Reposted by Patrick Murphy

Hiten Madhani @hitenmadhani.bsky.social · 21/03/2026

Very sad to hear of the passing today of our UCSF colleague Mike Bishop at the age of 90. A legendary and inspiring figure. He also led UCSF as Chancellor. Have a listen to his Nobel lecture. youtube.com/watch?v=CDv7...

youtube.com

Michael Bishop, Nobel Prize in Physiology or Medicine 1989: Official Lecture

YouTube video by Nobel Prize

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Reposted by Patrick Murphy

Hao Yin @haoyin.bsky.social · 15/03/2026

A mouse model of Nose bleeding #HereditaryHemorrhagicTelangiectasia Bmx+ Endothelial Cell ALK1 KO🐭 +🧠microhemorrhage Arterial tortuosity, ectasia Arteriolar smooth muscle cell wrapping defects ⏬pial/mesenteric arterial tone @mfnavedo.bsky.social #CircRes 2026 www.ahajournals.org/doi/10.1161/...

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Reposted by Patrick Murphy

Michael D. Green, PhD @michaeldgreen.phd · 26/02/2026

I had to renegotiate my F99/K00 award twice in 6 months, and on both occasions I asked what specifically “DEI activities” means. I didn’t get clear answers, so I was hopeful the person that directive came from could specify (the NIH Director). I asked the on @whyshoulditrustyou.bsky.social podcast

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Reposted by Patrick Murphy

Gan Lab @liganlab.bsky.social · 26/02/2026

Excited to share our new preprint showing cGAS mediates innate immune activity in TDP-43 proteinopathy. Pharmacological inhibition of cGAS restores microglial function, corrects RNA mis-splicing, & protects motor neurons across human iPSC & mouse models of ALS www.biorxiv.org/content/10.6...

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Reposted by Patrick Murphy

Timothy Hla @hlatim.bsky.social · 22/02/2026

Upcoming Gordon Research Conference on ENDOTHELIAL CELLS Spain (July 5-10, 2026).The latest breaking topics in vascular biology focused on endothelial cells will be featured. Open slots reserved for oral presentations. Register early to reserve your spot. www.grc.org/endothelial-...

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Reposted by Patrick Murphy

NAVBO @navbo.bsky.social · 20/02/2026

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Reposted by Patrick Murphy

Mark Peifer (He, him) @peiferlabunc.bsky.social · 21/02/2026

This is perhaps the most tragic of the consequences of the attack by Trump and colleagues on NIH. Gutting the next generation of American science 🧪

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Finally, and most importantly, the work has been spearheaded though the hard work and unwavering effort of Chris Pathoulas, with help from Amy Kimble in my own lab, and support from NHLBI and NIH, and @americanheart.bsky.social

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

We thank the patients who have donated tissue, our collaborators at UCLA, Harvard/MGH and Duke, and our local collaborators Antoine Menoret and Anthony Vella, who provided expertise in immune cell analysis, and Bing Hao and Yungfeng Li, who aided in antibody conjugations.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

ECs are ~1/3 of all of the cells in the heart, and directly accessible to perfusion systems prior to transplant - making them a powerful and still overlooked target for future therapeutics.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Thus, ECs can limit the immune response in transplanted tissues as effectively as broad immunosuppression. This means that these cells could be targeted to limit long term transplant damage – without requiring systemic suppression and its secondary consequences, increased infection and cancer.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

By CITE-seq analysis (<100 surface markers, together with mRNA levels) in mouse heart transplant +/- EC PTBP1, we find that although the total number of immune cells is not altered, that the nature of the response is. It becomes less activated, with lower activation of both T and NK subsets.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Indeed, Chris found that deletion of PTBP1 in human ECs cells limited hypoxia induced mitochondrial fragmentation and loss.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Computational analysis of the PTBP1 deficient ECs in the mouse transplants revealed transcriptional similarities to protected (no CAV) human transplant ECs. Transcripts were closely tied with cellular metabolism, suggesting that PTBP1 may limit metabolic dysfunction in the transplanted heart ECs.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Strikingly, hearts deleted for EC PTBP1 exhibited little development of CAV, fibrosis or hypoxia. These were reduced to the level of antibody mediated depletion of all NK and CD8 T cells in the same model.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Nicole introduced us to Drs. Joren Madsen and Alessandro Alessandrini at the Cardiothoracic Transplantation Lab @harvard.edu @massgeneralbrigham.bsky.social . With the help of Sandro, we used our PTBP1 EC-KO model to directly test importance in CAV in their mouse model.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

It became apparent that PTBP1, a splice factor we had identified as critical for EC activation through in vitro CRISPR KO screens, and in vivo in atherogenesis (www.pnas.org/doi/10.1073/...) was linked to CAV EC dysfunction, but lacked mechanistic insight.

pnas.org

Splice factor polypyrimidine tract-binding protein 1 (Ptbp1) primes endothelial inflammation in atherogenic disturbed flow conditions | PNAS

NF-κB–mediated endothelial activation drives leukocyte recruitment and atherosclerosis, in part through adhesion molecules Icam1 and Vcam1. The end...

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

As the project gained speed, through Chris’ dedicated efforts, we expanded the work to examine end stave cardiac allograft vasculopathy as well, and found a tremendous resources and collaborators in @jeffhsumd.bsky.social at UCLA and Dawn Bowles at @dukevascular.bsky.social .

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Chris Pathoulas, an incoming MD/PhD student in the lab, dedicated himself to isolating nuclei from the very small biopsy remnants.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Nicole, to her great credit, leaned into this, as we worked out how to apply inCITE-seq approaches (www.nature.com/articles/s41...) to assess alterations in biopsy. Protein levels are key, since mRNA levels of splice factors autoregulate (though “poison exons”), so mRNA often oppose protein level.

nature.com

Endothelial TDP-43 depletion disrupts core blood–brain barrier pathways in neurodegeneration - Nature Neuroscience

Targeting the endothelium across ages and neurodegenerative diseases in 92 donors with single-cell inCITE-seq reveals similar alterations in ~40% of capillaries in AD, ALS and FTD. Endothelial TDP-43 ...

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

For us, it was an exciting possibility to observe changes in the endothelium over time in humans, in their adaptation to immune responses. Our email correspondence at the time :

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

It began at an @ahajournals.bsky.social poster in 2018, when I met Dr. Nicole Valenzuela (UCLA then, now Maine Health). I was astounded to learn that it was routine for transplant heart tissues to be biopsied over time, and that she had been seeing EC prediction of dysfunction in these.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

Well-known for acute recruitment of immune and inflammatory cells from blood to tissue (via ICAM1, VCAM, selectins), their role in the instruction of immune and inflammatory cells after arrival remains much less understood.

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Patrick Murphy @1patrickmurphy.bsky.social · 20/02/2026

We are excited to share a new discovery in heart transplant www.biorxiv.org/cgi/content/..., which shows a critical role for the endothelium in organizing long term immune responses, and cardiac allograft vasculopathy.

biorxiv.org

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Patrick Murphy @1patrickmurphy.bsky.social · 14/11/2025

Noor can, and it was an amazing and inspirational learning experience to hear about her work. Thanks for your visit, and best of luck in continuing to develop your really exciting and powerful delivery system to cancer environment. Only afterwards did I realize I had forgotten to get a photo!

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Patrick Murphy @1patrickmurphy.bsky.social · 14/11/2025

It was pleasure to host my former lab mate Noor Jailkhani from Matrisome Bio yesterday at The University of Connecticut School of Medicine. Not many can say that they both developed a new technology hands on, and then led this into the market as the CEO of a successful company.

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Reposted by Patrick Murphy

Payam Gammage @mito-oncogene.bsky.social · 03/11/2025

Excited to share our latest work in collaboration with the @edreznik.bsky.social lab @mskcancercenter.bsky.social, where we describe functionally dominant mitochondrial DNA mutations in patient tumors. So, what is functional dominance in mitochondrial genetics, I hear you ask? rdcu.be/eN1jm

rdcu.be

Functionally dominant hotspot mutations of mitochondrial ribosomal RNA genes in cancer

Nature Genetics - Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and...

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Patrick Murphy @1patrickmurphy.bsky.social · 05/06/2025

Happy to share an exciting paper from my former lab mate, Jess Hebert, showing Cas12 efficacy and use in somatic screening. Take a look if you are considering the approach! www.nature.com/articles/s41...

nature.com

Efficient and multiplexed somatic genome editing with Cas12a mice - Nature Biomedical Engineering

Multiplexed editing using Cas12a transgenic mice facilitates the study of disease models with complex genotypes.

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Patrick Murphy @1patrickmurphy.bsky.social · 17/04/2025

Congratulations to Ashok, an exceptionally talented scientist who would be a tremendous junior faculty hire. Thank you to collaborators Riqiang Yan, Cat Lutz and Aamir at JAX, members of the Murphy lab, thoughtful input from reviewers and at CSH and Gordons Brain Barriers Meetings, and the NIH.

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Patrick Murphy @1patrickmurphy.bsky.social · 17/04/2025

Future questions: - Does endothelial TDP-43 dysfunction initiate motor neuron impairment in ALS? - Why is endothelial TDP-43 lost in AD and ALS-FTD without TDP-43 mutation (and vice versa how do some with familial mutation avoid disease)? - How does loss of TDP-43 lead to barrier defects?

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Patrick Murphy @1patrickmurphy.bsky.social · 17/04/2025

Moreover, Ashok observed changes in pathways that resembled those we had observed in capillary endothelial cells in ALS-FTD and AD of human donors. Together, this work suggests that brain endothelial TDP-43 dysfunction contributes to cognitive dysfunction.

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Patrick Murphy @1patrickmurphy.bsky.social · 17/04/2025

To more carefully examine brain endothelial function, Ashok used Slco1a1-CreERT2, and found acute BBB leak, and chronic fibrin deposition, basement membrane changes, gliosis, and pTau accumulation in neurons that ultimately lead to behaviors (social and memory) resembling a mouse model of FTD.

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Patrick Murphy @1patrickmurphy.bsky.social · 17/04/2025

Despite similar levels of the Tardbp mRNA, nuclear TDP-43 protein was reduced. Endothelial function was tested in Cdh5-CreERT2; Tardbp floxed mice, but systemic endothelial dysfunction limited understanding of organ specific functions.

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