Karen Hirschi, PhD
Professor AdjunctCards
About
Research
Publications
2024
Endothelial-adipocyte Cx43 mediated gap junctions can regulate adiposity
Luse M, Dunaway L, Nyshadham S, Carvalho A, Sedovy M, Ruddiman C, Tessema R, Hirschi K, Johnstone S, Isakson B. Endothelial-adipocyte Cx43 mediated gap junctions can regulate adiposity. Function 2024, zqae029. PMID: 38984993, DOI: 10.1093/function/zqae029.Peer-Reviewed Original ResearchHigh-fat dietHigh-fat diet miceGap junctionsIncreased risk of cardiovascular diseaseUpregulation of fatty acid-binding protein 4Co-culture transwell systemPhosphorylation of Cx43Adipose endothelial cellsRisk of cardiovascular diseaseImproved lipid profileFatty acid binding protein 4Endothelial Cx43Adipocytes in vitroAdipose tissue functionBinding protein 4Post-translational modificationsEpididymal fat padsHeterocellular contactsSingle-cell RNA sequencingEndothelial dysfunctionSerine 368Cx43Heterocellular communicationLipid profileGenetic deletionDisruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure
Horitani K, Chavkin N, Arai Y, Wang Y, Ogawa H, Yura Y, Evans M, Cochran J, Thel M, Polizio A, Sano M, Miura-Yura E, Arai Y, Doviak H, Arnold A, Gelfand B, Hirschi K, Sano S, Walsh K. Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure. Nature Cardiovascular Research 2024, 3: 343-355. DOI: 10.1038/s44161-024-00441-z.Peer-Reviewed Original ResearchHeart failureHigher incidence of heart failureHigher incidenceProgression of heart failureIncidence of heart failureY chromosome lossCardiac fibroblast activationProfibrotic macrophagesDilated cardiomyopathyHematopoietic cellsMale miceFailing heartIncreased riskEpigenetic alterationsFibroblast activationMosaic lossLeukocytesUTIMacrophagesHearts of humansAccelerated progressionRegulator locusHeartGene expressionY chromosome
2023
Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Genet G, Genet N, Paila U, Cain S, Cwiek A, Chavkin N, Serbulea V, Figueras A, Cerdà P, McDonnell S, Sankaranarayanan D, Huba M, Nelson E, Riera-Mestre A, Hirschi K. Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. Circulation 2023, 149: 944-962. PMID: 38126211, PMCID: PMC10954087, DOI: 10.1161/circulationaha.122.062952.Peer-Reviewed Original ResearchHereditary hemorrhagic telangiectasiaArteriovenous malformationsVascular malformationsHemorrhagic telangiectasiaCDK 4/6 inhibitor palbociclibCell cycle G1 arrestCell cycle stateG1 arrestEndothelial-specific deletionInhibitor palbociclibLate G1 arrestPalbociclib treatmentArteriovenous shuntsDrug AdministrationTherapeutic potentialGenetic deletionType 1Cell cycle controlEndothelial cell cycleMalformationsArteriovenous identityEndothelial cell migrationAVM developmentPalbociclibCycle controlObesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium
Dunaway L, Luse M, Nyshadham S, Bulut G, Alencar G, Chavkin N, Cortese-Krott M, Hirschi K, Isakson B. Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium. Physiological Genomics 2023, 56: 113-127. PMID: 37982169, PMCID: PMC11281809, DOI: 10.1152/physiolgenomics.00109.2023.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingMitochondrial gene expressionGene expressionRNA sequencingOxidative phosphorylation gene expressionHigh-fat dietTranscription factor analysisSingle-nucleus RNAEndothelial cellsCapillary endothelial cellsAdipose endothelial cellsMitochondrial genesPhenotypic convergenceMesenteric endothelial cellsTranscriptional phenotypeBulk RNALipid homeostasisPeroxisome proliferator-activated receptorDistinct rolesPhenotypic shiftNovel mechanismMouse AdiposeProliferator-activated receptorResident tissuesDownregulation of PPAR
Links & Media
News
- February 10, 2022
Yale Scientists Identify a Gene That Can Repair Congenital Heart Defects
- January 25, 2021Source: CBS News
UVA Health blood discoveries help efforts to grow organs, fight cancer
- December 03, 2020Source: Nature
A sugary coating tells cells it’s time to make blood
- December 02, 2020
Yale Scientists Unlock “Sugar Code” to Regulate in vivo and ex-vivo Blood Stem Cell Production