Joseph Madri, MD/PhD
Cards
Appointments
Contact Info
About
Titles
Professor Emeritus of Pathology
Appointments
Pathology
EmeritusPrimary
Other Departments & Organizations
Education & Training
- Fellow
- Yale University School of Medicine (1980)
- Resident
- Yale-New Haven Hospital (1977)
- MD/PhD
- Indiana University, Biological Chemistry and Medicine (1975)
Research
Overview
Research Focus: The interests of my laboratory center around investigations of signaling pathways stimulated following endothelial cell-cell and endothelial cell-extracellular interactions and how they influence the processes of vasculogenesis, angiogenesis and transendothelial migration.
Endothelial cells play central roles in the development, growth and maintenance of the vascular system as well as in the processes of inflammation, repair and metastasis. Vascular cell homotypic and heterotypic interactions and vascular cell interactions with the surrounding matrix, soluble factors and circulating blood cells (leukocytes, monocytes and lymphocytes), in part, direct the vascular cells' responses; yet little is known about these complex interactions and the mechanisms involved in information transduction from the extracellular environment to the cell nucleus.
We are currently investigating the roles of selected homotypic and heterotypic cell adhesion molecules (PECAM-1 & CD44), integrins (selected beta1, beta 2 and beta 3 integrins), junction associated molecules (VE-cadherin, ZO-1, Occludin) and extracellular matrix components (MMPs) in modulating vascular cell and T cell behavior (attachment, spreading, proliferation, migration, interactions with mononuclear (T) cells and angiogenesis).
Specific projects in the laboratory currently include:
1) Elucidation of the roles of the cytoplasmic domains of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1/CD31) and CD44 in modulating endothelial and T cell behavior, vascular development and dermal wound healing as well as the signaling mechanisms involved. We are investigating how differential tyrosine and serine phosphorylation of the PECAM-1 cytoplasmic domain modulates associations with specific proteins including beta- and gamma-catenin; STAT3&5, c-src, SHP-2 and small G proteins. We are also investigating the dynamic interactions between CD44 and CD31.
2) Identification and elucidation of the signal transduction pathways activated following T cell-endothelial cell binding and subsequent CD44 and PECAM-1 signaling prior to, during and following T cell transmigration into tissues. We are investigating the mechanisms of induction, clustering and activation of T cell and endothelial cell matrix metalloproteinase-2 [MMP-2 ], membrane type matrix metalloproteinase [MT1-MMP/MMP-14], matrix metalloproteinases [MMP-9] and CD44. Selected knock out mouse strains (CD44 KO) are also utilized in animal models of autoimmune encephalomyelitis.
3) Elucidation of the mechanisms of hypoxia-driven cerebral angiogenic responses noted in the premature infant population and their association with neurodevelopmental handicaps. Animal, organ and tissue culture models of chronic hypoxia, coupled with cDNA array analysis, are used to investigate the responses of the cerebral microvascular endothelial cells and the roles of the vasculature in causing resultant neurodevelopmental handicaps. The dynamic roles of HIF-1alpha and Sox10 in endothelial and neural stem cell responses to, and recovery from, hypoxic insult are being investigated.
1) Elucidation of the mechanisms involved in the recovery of neurodevelopmental handicaps incurred during and following premature birth and recovery from spinal cord injury.
3) Elucidation of the mechanisms involved in lymphocyte transmigration through endothelial cells during inflammation.
4) Elucidation of the roles of PECAM-1 (CD31) and CD44 in vasculo- and angiogenesis, permeability, inflammation, directed migration, hemostasis and hematopoiesis and bone metabolism.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Bauer Sumpio, MD, PhD, FACS
Sandra Canosa, MSc, CCRP
Michael Schwartz, PhD
Roland Assi, MD, MMS
David Schoenfeld, MD, PhD
Mehran M Sadeghi, MD
Endothelial Cells
Inflammation
T-Lymphocytes
Connective Tissue Diseases
Publications
2023
CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer’s disease
Zhang Z, Gan Q, Han J, Tao Q, Qiu W, Madri J. CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer’s disease. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 1027-1041. PMID: 37051650, PMCID: PMC10291450, DOI: 10.1177/0271678x231170041.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPlatelet endothelial cell adhesion moleculeImmune cellsDisease riskBlood-brain barrier permeabilityMajor genetic risk factorBlood-brain barrierNeuronal cell injuryEndothelial cell adhesion moleculesAlzheimer's disease riskGenetic risk factorsPeripheral inflammationBrain axisAPOE4 carriersAD pathogenesisRisk factorsBarrier permeabilityAD developmentCell adhesion moleculeCell injuryImmune systemAlzheimer's diseaseCD31Transendothelial migrationPotential drug targetsAdhesion molecules
2020
Glycocalyx‐Like Hydrogel Coatings for Small Diameter Vascular Grafts
Dimitrievska S, Wang J, Lin T, Weyers A, Bai H, Qin L, Li G, Cai C, Kypson A, Kristofik N, Gard A, Sundaram S, Yamamoto K, Wu W, Zhao L, Kural M, Yuan Y, Madri J, Kyriakides T, Linhardt R, Niklason L. Glycocalyx‐Like Hydrogel Coatings for Small Diameter Vascular Grafts. Advanced Functional Materials 2020, 30 DOI: 10.1002/adfm.201908963.Peer-Reviewed Original ResearchCitationsA Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells
Boisvert E, Means R, Michaud M, Thomson J, Madri J, Katz S. A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells. Journal Of Visualized Experiments 2020 DOI: 10.3791/60379-v.Peer-Reviewed Case Reports and Technical NotesA Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells.
Boisvert EM, Means RE, Michaud M, Thomson JJ, Madri JA, Katz SG. A Static Self-Directed Method for Generating Brain Organoids from Human Embryonic Stem Cells. Journal Of Visualized Experiments 2020 PMID: 32202516, PMCID: PMC7245934, DOI: 10.3791/60379.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsEmbryonic stem cellsCell typesStem cellsIntrinsic developmental cuesHuman embryonic stem cellsHuman pluripotent stem cellsBrain organoidsBrain cell typesPluripotent stem cellsBasement membrane matrixMultiple cell typesDevelopmental cuesUse of organoidsExogenous growth factorsQuantitative reverse transcription polymerase chain reactionMultitude of diseasesHuman brain organoidsOrganoid growthSingle cellsReal-time quantitative reverse transcription polymerase chain reactionSpatial organizationOrganoidsGenetic disordersGrowth factorReverse transcription-polymerase chain reaction
2019
Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report
Roque A, Kimbrough T, Traner C, Baehring JM, Huttner A, Adams J, Canosa S, Sklar J, Madri JA. Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report. Journal Of Medical Case Reports 2019, 13: 389. PMID: 31874650, PMCID: PMC6930684, DOI: 10.1186/s13256-019-2317-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsBrain NeoplasmsCarney ComplexChemoradiotherapyCyclic AMP-Dependent Protein Kinase RIalpha SubunitDopamine AgentsExome SequencingFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorGerm-Line MutationHeart NeoplasmsHumansIntracranial HemorrhagesMemantineMiddle AgedMyxomaTreatment OutcomeConceptsAtrial myxomaSporadic tumorsExtra-cardiac complicationsMetastatic cardiac myxomaMajority of tumorsDissemination of tumorsIntracranial hemorrhagic lesionsWhole-exome sequencingAutosomal dominant conditionConclusionsOur patientsSporadic myxomasInvasive tumor cellsParenchymal metastasesCardiac myxomaCase reportClinical behaviorHemorrhagic lesionsAneurysm formationBenign neoplasmsMyxomaSporadic lesionsVascular wallCarney complexTumorsGermline mutationsMinocycline mitigates the effect of neonatal hypoxic insult on human brain organoids
Boisvert EM, Means RE, Michaud M, Madri JA, Katz SG. Minocycline mitigates the effect of neonatal hypoxic insult on human brain organoids. Cell Death & Disease 2019, 10: 325. PMID: 30975982, PMCID: PMC6459920, DOI: 10.1038/s41419-019-1553-x.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNeonatal hypoxic injuryBrain developmentEfficacy of minocyclineLow birth weightUse of minocyclineEffects of hypoxiaNormal brain developmentCerebral organoid modelHuman brain organoidsLater time pointsAnimal model systemsNeonatal hypoxicDevastating causeCerebral palsySignificant morbidityHuman brain developmentNeurological consequencesBirth weightHypoxic injuryNeuronal deathCortical neuronsInjury resultsGlial cellsForebrain markersPotential treatment
2018
Immunocytochemical Techniques in Connective Tissue Research
Roll F, Madri J. Immunocytochemical Techniques in Connective Tissue Research. 2018, 49-88. DOI: 10.1201/9781351073424-3.Peer-Reviewed Original ResearchCitationsThe Immunobiology and Immunogenetics of the Collagens*
Kemp J, Madri J. The Immunobiology and Immunogenetics of the Collagens*. 2018, 175-186. DOI: 10.1201/9781351073424-7.Peer-Reviewed Original Research
2017
MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors
Li Q, Michaud M, Shankar R, Canosa S, Schwartz M, Madri JA. MMP-2: A modulator of neuronal precursor activity and cognitive and motor behaviors. Behavioural Brain Research 2017, 333: 74-82. PMID: 28666838, DOI: 10.1016/j.bbr.2017.06.041.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAnimalsAnimals, NewbornCell MovementCell ProliferationCells, CulturedCognitionExploratory BehaviorGene Expression RegulationMatrix Metalloproteinase 2MiceMice, Inbred C57BLMice, KnockoutMotor ActivityNerve Tissue ProteinsNeural Stem CellsNeurogenesisOncogene Protein v-aktProliferating Cell Nuclear AntigenReceptors, CXCR4Spatial LearningConceptsNeural precursor cellsBroad substrate specificityNeurosphere formationAdherent neurospheresSecondary neurosphere formationNPC activitySubstrate specificityNPC numberCell surface moleculesZinc-containing enzymesAkt activationAbsence of MMP2Cell typesExtracellular matrixActivity assaysPrecursor cellsImportant roleNPC migrationMatrix metalloproteinase2Surface moleculesExpressionKO miceBioactive moleculesNestin expressionMMP2CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation
Kuwahara G, Hashimoto T, Tsuneki M, Yamamoto K, Assi R, Foster TR, Hanisch JJ, Bai H, Hu H, Protack CD, Hall MR, Schardt JS, Jay SM, Madri JA, Kodama S, Dardik A. CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1147-1156. PMID: 28450292, PMCID: PMC5467640, DOI: 10.1161/atvbaha.117.309385.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsExtracellular matrix depositionKnockout miceExtracellular matrix componentsExtracellular matrix productionMatrix depositionAdhesion molecule-1 expressionM2 macrophagesProtein 1Matrix productionCell adhesion molecule-1 expressionMolecule-1 expressionProtein expressionMatrix componentsCD44 knockout miceProtein-1 expressionMajor receptorCD44 activityMaturationVascular cell adhesion molecule-1 expressionAdhesion moleculesExpressionCD44 mRNAChemoattractant protein-1 expressionWild-type C57BL/6JArteriovenous fistula
Academic Achievements and Community Involvement
activity Cardiovascular Research
ResearchDetails01/01/2011 - PresentUnited KingdomAbstract/SynopsisYale-Cambridge Program in Cardiovascular Research that focuses on arteriosclerosis, angiogenesis, vascular injury, and transplantation.
honor Chugai Award for Meritorious Mentorship & Scholarship from the
National AwardAmerican Society for Investigative PathologyDetails04/20/2001United Stateshonor NIH MERIT Award
National AwardNIHDetails01/01/1999United States
Links & Media
News
- June 24, 2024
Foundation Created by Joseph Madri, MD/PhD, Professor Emeritus of Pathology, Supports Many Causes
- April 12, 2022
Yale Pathology Meets in Madison for Department Retreat; First In-Person Gathering Since Pandemic Began
- January 31, 2017
New endowed professorship established in experimental pathology
- November 12, 2014
Can resilience be engineered?
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