2023
A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension
Gunawardhana K, Hong L, Rugira T, Uebbing S, Kucharczak J, Mehta S, Karunamuni D, Cabera-Mendoza B, Gandotra N, Scharfe C, Polimanti R, Noonan J, Mani A. A systems biology approach identifies the role of dysregulated PRDM6 in the development of hypertension. Journal Of Clinical Investigation 2023, 133: e160036. PMID: 36602864, PMCID: PMC9927944, DOI: 10.1172/jci160036.Peer-Reviewed Original ResearchConceptsDevelopment of hypertensionParallel reporter assaysRenin inhibitor aliskirenNeural crest-derived cellsRenin-producing cellsSystems biology approachRNA-seq analysisCell-specific disruptionCrest-derived cellsSmooth muscle cellsMuscle cell proteinsSystemic hypertensionBlood pressureWT miceAntihypertensive drugsBiology approachSuper enhancersFine mappingWT littermatesThird intronMultiple GWASCollagen depositionMouse aortaReporter assaysFate mapping
2020
Massively parallel discovery of human-specific substitutions that alter enhancer activity
Uebbing S, Gockley J, Reilly SK, Kocher AA, Geller E, Gandotra N, Scharfe C, Cotney J, Noonan JP. Massively parallel discovery of human-specific substitutions that alter enhancer activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 118: e2007049118. PMID: 33372131, PMCID: PMC7812811, DOI: 10.1073/pnas.2007049118.Peer-Reviewed Original ResearchConceptsHuman-specific substitutionsHuman-gained enhancersGenetic changesEnhancer functionEnhancer activityHuman-specific genetic changesHuman evolutionGene regulatory elementsBackground genetic variationAncestral functionRegulatory evolutionEnhancer assaysGenetic variationRegulatory elementsNeural stem cellsHuman traitsNovel activityNonadditive wayRegulatory activityStem cellsFunctional impactDifferential activityParallel discoveryEnhancerEvolution
2012
Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism
St.Onge R, Schlecht U, Scharfe C, Evangelista M. Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism. Molecules 2012, 17: 13098-13115. PMID: 23128089, PMCID: PMC3539408, DOI: 10.3390/molecules171113098.Peer-Reviewed Original ResearchConceptsChemical geneticsChemical probesCellular metabolismDominant model organismChemical genetic screeningForward chemical geneticsHigh-throughput phenotypicDrug target identificationNormal cellular metabolismNew chemical probesHigher eukaryotesExperimental tractabilityModel organismsYeast SaccharomycesCellular processesIdeal organismNew druggable targetsMolecular biologyYeastDruggable targetsGeneticsDiseased statesOrganismsGenetic screeningMetabolism
2006
MitoP2: the mitochondrial proteome database—now including mouse data
Prokisch H, Andreoli C, Ahting U, Heiss K, Ruepp A, Scharfe C, Meitinger T. MitoP2: the mitochondrial proteome database—now including mouse data. Nucleic Acids Research 2006, 34: d705-d711. PMID: 16381964, PMCID: PMC1347489, DOI: 10.1093/nar/gkj127.Peer-Reviewed Original ResearchConceptsMitochondrial proteinsSystematic genome-wide studiesMitochondrial proteome databaseNovel mitochondrial proteinGenome-wide studiesSystems biology approachOrthologous proteinsMolecular functionsBiology approachProteome databaseRare mitochondrial diseaseMitochondrial diseasePhenotype screeningMitochondrial dysfunctionReference proteinProteinMitochondriaMouse dataMitoP2ProteomicsIntegration of dataYeastGenesSpeciesPathway
2005
Identifying new candidate genes for hereditary facial paresis on chromosome 3q21–q22 by RNA in situ hybridization in mouse
van der Zwaag B, Burbach JP, Scharfe C, Oefner PJ, Brunner HG, Padberg GW, van Bokhoven H. Identifying new candidate genes for hereditary facial paresis on chromosome 3q21–q22 by RNA in situ hybridization in mouse. Genomics 2005, 86: 55-67. PMID: 15953540, DOI: 10.1016/j.ygeno.2005.03.007.Peer-Reviewed Original ResearchConceptsHereditary congenital facial paresisNew candidate genesMouse developmentCandidate genesSitu hybridizationTranscription-PCR analysisUndetectable expression levelsMouse embryogenesisPositional candidatesExpression analysisUbiquitous expressionGenesMeans of RNAExpression levelsGenetic defectsRNADisease familiesHybridizationCongenital cranial dysinnervation disordersExpressionFacial paresisCranial dysinnervation disordersEmbryogenesisChromosomesFamily
2000
MITOP, the mitochondrial proteome database: 2000 update
Scharfe C, Zaccaria P, Hoertnagel K, Jaksch M, Klopstock T, Dembowski M, Lill R, Prokisch H, Gerbitz KD, Neupert W, Mewes HW, Meitinger T. MITOP, the mitochondrial proteome database: 2000 update. Nucleic Acids Research 2000, 28: 155-158. PMID: 10592209, PMCID: PMC102491, DOI: 10.1093/nar/28.1.155.Peer-Reviewed Original ResearchConceptsGene catalogProtein entriesComplete yeast genomeHuman diseasesMitochondrial-encoded proteinsMitochondrial proteome databaseNew mitochondrial proteinsMitochondrial proteomeYeast genomeCaenorhabditis elegansProtein catalogueMitochondrial proteinsEST hitsNeurospora crassaProteome databaseHomology searchSpecies FileMitoPSInterspecies relationshipsFASTA searchGenetic characterizationMus musculusReference sequenceEscherichia coliHomo sapiens
1999
MITOP: database for mitochondria-related proteins, genes and diseases
Scharfe C, Zaccaria P, Hoertnagel K, Jaksch M, Klopstock T, Lill R, Prokisch H, Gerbitz K, Mewes HW, Meitinger T. MITOP: database for mitochondria-related proteins, genes and diseases. Nucleic Acids Research 1999, 27: 153-155. PMID: 9847163, PMCID: PMC148118, DOI: 10.1093/nar/27.1.153.Peer-Reviewed Original ResearchConceptsGene catalogProtein entriesMitochondrial-encoded genesMitochondria-related proteinsCaenorhabditis elegansProtein catalogueEST hitsMitochondrial processesNeurospora crassaFASTA searchInterspecies homologyMus musculusReference sequenceHomologyGenesProteinFacilitate investigationProtein abnormalitiesSequenceElegansCrassaCerevisiaeMusculusSpeciesPathway
1998
Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD) Caused by Mutations in a Novel Gene (Wolframin) Coding for a Predicted Transmembrane Protein
Strom T, Hörtnagel K, Hofmann S, Gekeler F, Scharfe C, Rabl W, Gerbitz K, Meitinger T. Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (DIDMOAD) Caused by Mutations in a Novel Gene (Wolframin) Coding for a Predicted Transmembrane Protein. Human Molecular Genetics 1998, 7: 2021-2028. PMID: 9817917, DOI: 10.1093/hmg/7.13.2021.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid SequenceAnimalsChildChromosomes, Human, Pair 4DNAExonsFamily HealthFemaleGenesGenetic MarkersHumansIntronsMaleMembrane ProteinsMiceMolecular Sequence DataMutationPedigreePhysical Chromosome MappingPolymorphism, Single-Stranded ConformationalSequence AlignmentSequence Analysis, DNASequence Homology, Amino AcidWolfram SyndromeConceptsOptic atrophyWolfram syndrome patientsJuvenile diabetes mellitusWolfram syndrome familiesAutosomal recessive disorderMitochondrial DNA deletionsDiabetes mellitusPeripheral neuropathyNeurological symptomsDiabetes insipidusPsychiatric illnessSyndrome patientsWolfram syndromeHeterozygous carriersRecessive disorderSyndrome familiesAffected individualsMellitusPatientsAtrophyInsipidusFunction mutationsDeafnessDNA deletionsTransmembrane protein