Michael Rubinstein, MD
About
Research
Publications
2024
The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences
Caporale A, Cinalli A, Rubinstein M, Franchini L. The Human Accelerated Region HAR202 Controls NPAS3 Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences. Molecular Biology And Evolution 2024, 41: msae186. PMID: 39241178, PMCID: PMC11461159, DOI: 10.1093/molbev/msae186.Peer-Reviewed Original ResearchArchaic humansHuman lineageLiving relativesNPAS3 expressionComparative functional analysisMouse developing brainNervous systemEnhancer reporter assaysZebrafish nervous systemOrthologous sequencesTransgenic miceDeveloping brainNucleotide substitutionsPhenotypic evolutionTranscriptional enhancersHuman sequenceChimpanzeesNeurodevelopmental genesCognitive abilitiesMiceHumansPhenotypic differencesHOMOReporter expressionExpression patternsThe homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice
Yu H, Chiang A, Rubinstein M, Low M. The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice. Molecular Metabolism 2024, 87: 101993. PMID: 39025297, PMCID: PMC11327434, DOI: 10.1016/j.molmet.2024.101993.Peer-Reviewed Original ResearchHypothalamic POMC expressionPOMC neuronsPOMC expressionFood intakeMild obesityDaily food intakeFemale micePOMC immunoreactivityAdult micePOMC-expressing neuronsSuppress food intakeMaintenance of physiological levelsPOMC mRNA levelsReduced POMC expressionBody weightKnockout mouse modelMouse hypothalamic neuronsIncreased daily food intakeCentral melanocortinEnhanced energy expenditureExpression of Six3Functional significanceMelanocortin neuronsHypothalamic neuronsAnorexigenic neuropeptidesAccelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus
Berasain L, Beati P, Trigila A, Rubinstein M, Franchini L. Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus. Science Advances 2024, 10: eadl1049. PMID: 38924416, PMCID: PMC11204294, DOI: 10.1126/sciadv.adl1049.Peer-Reviewed Original ResearchConceptsTranscriptional enhancersGoal of evolutionary biologyHuman lineageZebrafish reporter assayGene regulatory networksPotential regulatory elementsHuman-specific traitsChimpanzee sequencesRBFOX1 locusRegulatory elementsRegulatory networksRegulatory modificationsEvolutionary biologyAccelerated evolutionTarget genesGene expressionGenesDevelopmental stagesLociLineagesReporter assayExpressionRBFOX1SplicingTemporal changesA mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight
Rojo D, Hael C, Soria A, de Souza F, Low M, Franchini L, Rubinstein M. A mammalian tripartite enhancer cluster controls hypothalamic Pomc expression, food intake, and body weight. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2322692121. PMID: 38652744, PMCID: PMC11067048, DOI: 10.1073/pnas.2322692121.Peer-Reviewed Original ResearchConceptsFood intakeControl of food intakeHypothalamic POMC expressionBody weight homeostasisHypothalamic arcuate neuronsConvergent evolutionary processesReporter gene expressionPurifying selectionArcuate neuronsDeletion eventsMouse genomeMolecular evolutionWeight homeostasisFemale miceAdult micePOMC expressionTranscriptional enhancersMutant miceEnhancer mutantsTranscription factorsPlacental mammalsMammalian ordersGene expressionMiceEvolutionary processHumanized dopamine D4.7 receptor male mice display risk‐taking behavior and deficits of social recognition and working memory in light/dark‐dependent manner
Alachkar A, Phan A, Dabbous T, Alhassen S, Alhassen W, Reynolds B, Rubinstein M, Ferré S, Civelli O. Humanized dopamine D4.7 receptor male mice display risk‐taking behavior and deficits of social recognition and working memory in light/dark‐dependent manner. Journal Of Neuroscience Research 2024, 102: e25299. PMID: 38361407, PMCID: PMC11503891, DOI: 10.1002/jnr.25299.Peer-Reviewed Original ResearchConceptsPsychiatric disordersBehavioral phenotypesImpaired social recognition memoryEtiology of psychiatric disordersAttention-deficit hyperactivity disorderDopamine D<sub>4</sub> receptor (DWorking memory deficitsSocial recognition memoryDark phaseRisk-taking behaviorRecognition memoryWorking memoryMemory deficitsR miceIncreased risk behaviorSocial recognitionSpecific behaviorsBehavioral featuresDisordersMale miceDopaminePotential causal relationshipRisk behaviorsLight phaseDeficits
2016
Hypothalamic Pomc ‐deficiency Impairs the Function of Leptin to Decrease Food Intake and Bodyweight
Chhabra K, Adams J, Jones G, Rubinstein M, Low M. Hypothalamic Pomc ‐deficiency Impairs the Function of Leptin to Decrease Food Intake and Bodyweight. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.1293.4.Peer-Reviewed Original ResearchFunction of leptinHistory of obesityNormal body weightPlasma leptin levelsKO miceFood intakeHypothalamic POMCBody weightLeptin levelsLeptin administrationLeptin sensitivityHigher plasma leptin levelsLeptin receptor gene expressionIntracerebroventricular leptin administrationMagnitude of obesityPomc knockout miceReversal of obesityWeight-matched miceDiabetes Research CenterNormal energy homeostasisWeight-matched groupsLongitudinal studyReceptor gene expressionARC POMCPrevents obesity
2002
Thrittene, Homologous with Somatostatin-28(1–13), Is a Novel Peptide in Mammalian Gut and Circulation
Ensinck J, Baskin D, Vahl T, Vogel R, Laschansky E, Francis B, Hoffman R, Krakover J, Stamm M, Low M, Rubinstein M, Otero-Corchon V, D’Alessio D. Thrittene, Homologous with Somatostatin-28(1–13), Is a Novel Peptide in Mammalian Gut and Circulation. Endocrinology 2002, 143: 2599-2609. DOI: 10.1210/en.143.7.2599.Peer-Reviewed Original ResearchMammalian gutS-28(1-12C-terminal domainAmino acid sequenceN-terminal regionC-terminal productGI endocrine cellsSite of synthesisEndocrine cellsPROS geneS-28Acid sequenceRatios of peptidesPreprosomatostatin genesC-terminusMolecular massDistal gutGenesS-14Proximal regionGutTract of ratsGut neuronsMyenteric neuronsMammalian neuronsDisruption of the D2 Dopamine Receptor Alters GH and IGF-I Secretion and Causes Dwarfism in Male Mice
Díaz-Torga G, Feierstein C, Libertun C, Gelman D, Kelly M, Low M, Rubinstein M, Becú-Villalobos D. Disruption of the D2 Dopamine Receptor Alters GH and IGF-I Secretion and Causes Dwarfism in Male Mice. Endocrinology 2002, 143: 1270-1279. DOI: 10.1210/en.143.4.1270.Peer-Reviewed Original ResearchKnockout miceMale miceD2 receptorsIGF-IGHRH-GH-IGF-I axisIGF-binding protein-3 levelsLoss of D2 receptorsGH-IGF-I axisD2R antagonist sulpirideD2R-/- miceBasal GH releaseKnockout male miceDopamine D2 receptorsIGF-I secretionSerum GH concentrationsWild-type miceAdult knockout miceImpaired body growthRate of skeletal maturationMonths of lifeMonths of ageD2R-/-Somatotrope populationAntagonist sulpirideGH release