Patrick Murphy
@1patrickmurphy.bsky.social
Associate Professor @ UConn Medical School. Endothelial cells, RNA biology, extracellular matrix, leukocyte-endothelial interactions.
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.
April 22, 2026 at 1:36 PM
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.
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.
April 22, 2026 at 1:36 PM
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.
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.
April 22, 2026 at 1:36 PM
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.
Elavl1 is enriched in the 5'UTR of transcripts at the ribosome (along with Zc3h10, which is known to regulate mRNA translation).
April 22, 2026 at 1:36 PM
Elavl1 is enriched in the 5'UTR of transcripts at the ribosome (along with Zc3h10, which is known to regulate mRNA translation).
Changes in mRNA at translating ribosomes (an important step to protein production) are very different for some mRNA than total mRNA levels.
April 22, 2026 at 1:36 PM
Changes in mRNA at translating ribosomes (an important step to protein production) are very different for some mRNA than total mRNA levels.
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.
February 20, 2026 at 3:58 PM
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.
February 20, 2026 at 3:58 PM
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.
February 20, 2026 at 3:58 PM
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.
February 20, 2026 at 3:58 PM
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.
Chris Pathoulas, an incoming MD/PhD student in the lab, dedicated himself to isolating nuclei from the very small biopsy remnants.
February 20, 2026 at 3:58 PM
Chris Pathoulas, an incoming MD/PhD student in the lab, dedicated himself to isolating nuclei from the very small biopsy remnants.
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 :
February 20, 2026 at 3:58 PM
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.
February 20, 2026 at 3:58 PM
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.
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.
November 14, 2025 at 12:14 AM
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.
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.
April 17, 2025 at 1:32 AM
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.
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.
April 17, 2025 at 1:32 AM
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.
What Ashok was able to show, by isolating and culturing brain endothelial cells, is that a single allele ALS-FTD mutation in TDP-43 disrupts formation of VE-cadherin junctions, cytoskeletal organization and barrier integrity.
April 17, 2025 at 1:32 AM
What Ashok was able to show, by isolating and culturing brain endothelial cells, is that a single allele ALS-FTD mutation in TDP-43 disrupts formation of VE-cadherin junctions, cytoskeletal organization and barrier integrity.
We then took advantage of the seq data in both projects, to examine the overlap in pathways affected in the TDP-43 low population of human capillary endothelial cells and cells with targeted TDP-43 disruption - and found many of the same pathways were hit.
December 14, 2023 at 8:59 PM
We then took advantage of the seq data in both projects, to examine the overlap in pathways affected in the TDP-43 low population of human capillary endothelial cells and cells with targeted TDP-43 disruption - and found many of the same pathways were hit.
This appears to allow canonical NF-kB transcription, as we find large changes in RNA transcript level in high NF-kB nuclei in AD, ALS and FTD, but not in cognitively healthy donors.
December 14, 2023 at 8:58 PM
This appears to allow canonical NF-kB transcription, as we find large changes in RNA transcript level in high NF-kB nuclei in AD, ALS and FTD, but not in cognitively healthy donors.
The combined analysis of TDP-43 and NF-kB showed a striking pattern. The two followed almost exactly the same pattern in endothelial cells from cognitively normal donors, with TDP-43 rising with NF-kB. However, in AD, ALS and FTD, there was a precipitous drop in nuclear TDP-43.
December 14, 2023 at 8:57 PM
The combined analysis of TDP-43 and NF-kB showed a striking pattern. The two followed almost exactly the same pattern in endothelial cells from cognitively normal donors, with TDP-43 rising with NF-kB. However, in AD, ALS and FTD, there was a precipitous drop in nuclear TDP-43.
However, we noticed a very different pattern of cell clustering in the data, and that the NF-kB high nuclei in the disease cluster were tightly packed, suggesting a unique transcriptional signature in these cells not apparent in the endothelial nuclei from unaffected donors.
December 14, 2023 at 8:57 PM
However, we noticed a very different pattern of cell clustering in the data, and that the NF-kB high nuclei in the disease cluster were tightly packed, suggesting a unique transcriptional signature in these cells not apparent in the endothelial nuclei from unaffected donors.
Oddly, however nuclear p65/NF-kB was not altered, although transcriptional analysis of this cluster showed that the NF-kB pathway was the most upregulated pathway in the cluster.
December 14, 2023 at 8:57 PM
Oddly, however nuclear p65/NF-kB was not altered, although transcriptional analysis of this cluster showed that the NF-kB pathway was the most upregulated pathway in the cluster.
Things became much more interesting when looking at the ECs. He found that there was disease associated cluster of capillary EC nuclei, with reduced TDP-43 and b-Catenin, a downstream transcription factor in the Wnt pathway criticial for BBB maintenance.
December 14, 2023 at 8:56 PM
Things became much more interesting when looking at the ECs. He found that there was disease associated cluster of capillary EC nuclei, with reduced TDP-43 and b-Catenin, a downstream transcription factor in the Wnt pathway criticial for BBB maintenance.
Then he showed in microglia that a previously described DAM population was NF-kB+ (and also ID’d an intermediate NF-kB population new to our knowledge).
December 14, 2023 at 8:55 PM
Then he showed in microglia that a previously described DAM population was NF-kB+ (and also ID’d an intermediate NF-kB population new to our knowledge).
Omar labeled several other antibodies for this inCITEseq approach to track levels of transcription factors key to BBB homeostasis, including NF-kB and b-Catenin. First, he validated the approach in siRNA treated cells, and in neurons where nuclear TDP-43 levels are known to drop.
December 14, 2023 at 8:55 PM
Omar labeled several other antibodies for this inCITEseq approach to track levels of transcription factors key to BBB homeostasis, including NF-kB and b-Catenin. First, he validated the approach in siRNA treated cells, and in neurons where nuclear TDP-43 levels are known to drop.
We wondered, if TDP-43 loss could have this large an impact, are EC levels altered in neurodegenerative disease. MD/PhD candidate
@omaruximab
led this, by combining a technique for EC nuclei enrichment we developed with a method to measure nuclear proteins and RNA #SingleCell
@omaruximab
led this, by combining a technique for EC nuclei enrichment we developed with a method to measure nuclear proteins and RNA #SingleCell
December 14, 2023 at 8:54 PM
We wondered, if TDP-43 loss could have this large an impact, are EC levels altered in neurodegenerative disease. MD/PhD candidate
@omaruximab
led this, by combining a technique for EC nuclei enrichment we developed with a method to measure nuclear proteins and RNA #SingleCell
@omaruximab
led this, by combining a technique for EC nuclei enrichment we developed with a method to measure nuclear proteins and RNA #SingleCell