@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
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...
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...
They are in good hands - but I can’t agree to root for the 3-peat. Let’s go Red Sox!
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...
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...
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/...
Considerations in the Use of Mouse Models of Vascular and Valvular Calcification
Our new article is now published in ATVB @ahascience.bsky.social
www.ahajournals.org/doi/10.1161/...
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
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...
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-...
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 🧪
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
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.
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.
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.
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.
Indeed, Chris found that deletion of PTBP1 in human ECs cells limited hypoxia induced mitochondrial fragmentation and loss.
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.
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.
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.
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.
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 .
Chris Pathoulas, an incoming MD/PhD student in the lab, dedicated himself to isolating nuclei from the very small biopsy remnants.
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.
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 :
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.
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.
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.