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Patrick A. Murphy, Ph.D.Associate Professor
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Education
Post-Graduate Training
Awards
| Degree | Institution | Major |
|---|---|---|
| Ph.D. | University of California, San Francisco | Biomedical Sciences |
| B.S., B.A. | Hamilton College | Biology and English |
Post-Graduate Training
| Training | Institution | Specialty |
|---|---|---|
| Postdoctoral | Massachusetts Institute of Technology | Richard Hynes Lab |
Awards
| Name of Award/Honor | Awarding Organization |
|---|---|
| North American Vascular Biology Meeting - Roundtable Discussion of Cell-Matrix Interactions in Vascular Remodeling | North American Vascular Biology Meeting |
| North American Vascular Biology Meeting Co-chair - Session Vascular Matrix Biology and Bioengineering Nano talks | North American Vascular Biology Meeting |
| Paul Dudley White International Scholar Award | American Heart Association |
| Finalist for the Irvine H. Page Junior Faculty Research Award | American Heart Association |
| Lab of the month | North American Vascular Biology Organization (NAVBO) |
| National Institutes of Health Pathway to Independence Award (R00) | National Institutes of Health - NHLBI |
| National Institutes of Health Pathway to Independence Award (K99) | National Institutes of Health - NHLBI |
| Postdoctoral Fellowship | American Heart Association |
| Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship (F32) | National Institutes of Health - NHLBI |
| Predoctoral Fellowship | American Heart Association |
| Name & Description | Category | Role | Type | Scope | Start Year | End Year |
|---|---|---|---|---|---|---|
| ImmunoCardiovascular Meeting | Professional/Scientific Organization | Organizer | UConn Health | Local | 2021 |
Disturbed blood flow patterns can lead to chronic inflammatory conditions in the arterial wall, a precipitating event in cardiovascular components of heart attack and stroke. The Murphy lab is dissecting the interactions between recruited immune cells and the arterial wall using inducible genetic models combined with intravital imaging, and in vitro co-culture models under varying flow regimes. We are endothelial-centric and focused on changes in alternative splicing and the sub-endothelial extracellular matrix induced by innate immune cell recruitment, which our data suggests play an important role in the progression of arterial inflammation. A deeper understanding of how the endothelium interacts with recruited immune cells will reveal ways to intervene with the processes underlying the growth and rupture of aneurysms and atherosclerotic plaques.
Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023
Journal Articles
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Splice factor polypyrimidine tract-binding protein 1 (Ptbp1) primes endothelial inflammation in atherogenic disturbed flow conditions.
Proceedings of the National Academy of Sciences of the United States of America 2022 Jul;119(30):e2122227119
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A method for rapid flow-cytometric isolation of endothelial nuclei and RNA from archived frozen brain tissue.
Laboratory investigation; a journal of technical methods and pathology 2021 Nov;
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Identification of splice regulators of fibronectin-EIIIA and EIIIB by direct measurement of exon usage in a flow-cytometry based CRISPR screen.
Scientific reports 2021 Oct;11(1):19835
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Alternative Splicing of FN (Fibronectin) Regulates the Composition of the Arterial Wall Under Low Flow.
Arteriosclerosis, thrombosis, and vascular biology 2021 Jan;41(1):e18-e32
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Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci.
American journal of physiology. Heart and circulatory physiology 2019 Apr;
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Activated T effector seeds: Cultivating atherosclerotic plaque through alternative activation.
American journal of physiology. Heart and circulatory physiology 2019 Mar;
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Endothelial FN (Fibronectin) Deposition by α5β1 Integrins Drives Atherogenic Inflammation.
Arteriosclerosis, thrombosis, and vascular biology 2018 Nov;38(11):2601-2614
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Alternative RNA splicing in the endothelium mediated in part by Rbfox2 regulates the arterial response to low flow.
eLife 2018 Jan;7
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Mouse Models of Cerebral Arteriovenous Malformation.
Stroke; a journal of cerebral circulation 2016 Jan;47(1):293-300
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Tumor angiogenesis in the absence of fibronectin or its cognate integrin receptors.
PloS one 2015 Jan;10(3):e0120872
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Constitutively active Notch4 receptor elicits brain arteriovenous malformations through enlargement of capillary-like vessels.
Proceedings of the National Academy of Sciences of the United States of America 2014 Dec;111(50):18007-12
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Alternative splicing of endothelial fibronectin is induced by disturbed hemodynamics and protects against hemorrhage of the vessel wall.
Arteriosclerosis, thrombosis, and vascular biology 2014 Sep;34(9):2042-50
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Notch4 normalization reduces blood vessel size in arteriovenous malformations.
Science translational medicine 2012 Jan;4(117):117ra8
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Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease.
Laboratory investigation; a journal of technical methods and pathology 2009 Sep;89(9):971-82
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Endothelial Notch4 signaling induces hallmarks of brain arteriovenous malformations in mice.
Proceedings of the National Academy of Sciences of the United States of America 2008 Aug;105(31):10901-6
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Splice Factor Polypyrimidine tract-binding protein 1 (Ptbp1) is Required for Immune Priming of the Endothelium in Atherogenic Disturbed Flow Conditions
| Title or Abstract | Type | Sponsor/Event | Date/Year | Location |
|---|---|---|---|---|
| Splice Factor Polypyrimidine tract-binding protein 1 (Ptbp1) is Required for Immune Priming of the Endothelium in Atherogenic Disturbed Flow Conditions | Poster | North American Vascular Biology Meeting | 2021 | Virtual |
| A Method for Rapid Flow-cytometric Isolation of Endothelial Nuclei and RNA from Archived Frozen Brain Tissue | Poster | North American Vascular Biology Meeting | 2021 | Virtual |
| Alternative Splicing in the Endothelium: Post-transcriptional Regulation in Arterial Inflammation | Talk | Albany Medical College | 2018 | Albany, NY |
| Alternative Splicing in the Endothelium: Post-transcriptional Regulation in Arterial Inflammation | Talk | Harvard | 2018 | Boston, MA |
| Dangerous Current: Genetic Dissection of Alternative Splicing Mechanisms in Flow-induced Arterial Inflammation | Talk | University of California, San Francisco | 2017 | San Francisco, CA |
| A Splice in Time: Alternative Splicing Regulation and Functions in Flow-induced Arterial Inflammation | Talk | Center for Excellence in Vascular Biology at Brigham and Women's Hospital | 2015 | Boston, MA |
| A Splice Odyssey : Alternative RNA Splicing Regulates Arterial Response to Innate Immune Cell Recruitment under Altered Flow | Talk | Boston Angiogenesis Meeting | 2015 | Boston, MA |
| Endothelial Regulation of the Arterial Subendothelial Matrix by Disturbed Flow: A Quantitative Transcriptomic and Proteomic Characterization | Talk | North American Vascular Biology Organization : Matrix Biology | 2015 | Hyannis, MA |
| A Splice Odyssey: an epic drama of alternative splicing in vascular inflammation | Talk | Massachusetts Institute of Technology | 2015 | Cambridge, MA |
| Macrophages induce an alternative splicing program in arterial endothelium exposed to disturbed flow | Talk | North American Vascular Biology Organization : Vascular Inflammation | 2014 | Monterey, CA |
| Alternative splicing of fibronectin protects against dissecting aneurysm | Talk | North American Vascular Biology Organization : Matrix Biology | 2013 | Hyannis, MA |
| Alternative splicing in the vascular response to pathological shear stress | Poster | NAVBO : International Vascular Biology Meeting | 2012 | Wiesbaden, GER |
| Notch reversibly converts veins to arteries and regulates arteriovenous hierarchy in mice | Talk | Cold Spring Harbor : Blood Brain Barrier | 2010 | Cold Spring Harbor, NY |
| Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease | Talk | North American Vascular Biology Organization : Genetics and Genomics | 2009 | Hyannis, MA |
| Endothelial expression of constitutively activated Notch4 promotes Brain Arterio-Venous Malformations (BAVM) and characteristics of stroke in mice | Talk | Gordon Research Conference : Angiogenesis and Microcirculation | 2007 | Newport, RI |