Paul Lombroso, MD
Cards
Appointments
Titles
Director, Laboratory of Molecular Neurobiology
Contact Info
Child Study Center
PO Box 207900, 230 South Frontage Road
New Haven, CT 06520-7900
United States
Appointments
Titles
Director, Laboratory of Molecular Neurobiology
Contact Info
Child Study Center
PO Box 207900, 230 South Frontage Road
New Haven, CT 06520-7900
United States
Appointments
Titles
Director, Laboratory of Molecular Neurobiology
Contact Info
Child Study Center
PO Box 207900, 230 South Frontage Road
New Haven, CT 06520-7900
United States
About
Titles
Professor Emeritus in the Child Study Center
Director, Laboratory of Molecular NeurobiologyAppointments
Child Study Center
EmeritusPrimary
Other Departments & Organizations
- Child & Adolescent Psychiatry Training Program
- Child Study Center
- Lombroso Lab
- Tic Disorder & Obsessive Compulsive Disorder Program
- WHRY Pilot Project Program Investigators
- Women's Health Research at Yale
- Yale Ventures
Education & Training
- NIMH/Merck Postdoctoral Fellow
- Child Study Center, Yale University (1990)
- Research Associate
- Laboratory of Cellular and Molecular Neuroscience, The Rockefeller University (1988)
- Chief
- Chief, Child and Adolescent Outpatient Clinic, St. Vincent's Hospital and Medical Center of New York (1987)
- MD
- Albert Einstein College of Medicine (1975)
- BA
- Harvard College (1972)
- Resident
- Bronx Mental Health Center
- Fellow
- Beth Israel Hospital
Board Certifications
Child & Adolescent Psychiatry
- Certification Organization
- AB of Psychiatry & Neurology
- Original Certification Date
- 1987
Psychiatry
- Certification Organization
- AB of Psychiatry & Neurology
- Original Certification Date
- 1980
Research
Overview
The Lombroso Lab studies how we normally learn and how these processes are disrupted in various neuropsychiatric disorders. We are interested in a number of disorders including Tourette’s syndrome, obsessive-compulsive disorder, autism, as well as drug addiction and Alzheimer’s disease. Our work focuses on a brain-specific protein tyrosine phosphatase called STEP and its role in regulating intracellular signaling.
Studies have shown that STEP expression is disrupted in over 10 different disorders. Some have have elevated levels of STEP while others have lower expression. Thus the current model is that optimal levels of STEP are required for proper synaptic function. Substrates of STEP include the kinases ERK1/2, Pyk2 and Fyn and dephosphorylation inactivates these enzymesem. STEP also regulates the cell surface expression of AMPA and NMDA glutamate receptors, and leads to their endocytosis. Signals that lead to the inactivation of STEP potentiate learning, while signals that lead to the activation of STEP oppose the development of synaptic plasticity. We use biochemical, molecular, immunocytochemical, and behavioral techniques to address the role that STEP plays in regulating aspects of learning.
- Identification and characterization of STEP inhibitors.
- Characterization of the STEP knock-out mouse.
- Regulation of glutamate receptor trafficking by STEP.
- Role of STEP in different disorders
- Phosphorylation of STEP and function of phosphorylation at specific sites.
Medical Subject Headings (MeSH)
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Jian Xu, PhD
Robert King, MD
Michael Bloch, MD, MS
Angus Nairn, PhD
Amy Arnsten, PhD
Euripedes C. Miguel, MD, PhD
Protein Tyrosine Phosphatases, Non-Receptor
Alzheimer Disease
Fragile X Syndrome
Schizophrenia
Publications
2020
Chapter 39 Obsessive–compulsive disorder
Bloch M, Artukoglu B, Lennington J, Szuhay G, Lombroso P. Chapter 39 Obsessive–compulsive disorder. 2020, 663-674. DOI: 10.1016/b978-0-12-813866-3.00039-4.Peer-Reviewed Original ResearchCitationsConceptsObsessive-compulsive disorderEvidence-based treatmentsCognitive behavioral therapyTreatment-refractory obsessive-compulsive disorderSignificant hereditary componentRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationBrain stimulantBehavioral therapyMagnetic stimulationCortico-striatoSelective serotonin reuptake inhibitorsPharmacological treatment strategiesFirst-line treatmentSerotonin reuptake inhibitorsAntipsychotic augmentationGenetic risk factorsReuptake inhibitorsDisordersRisk factorsTreatment strategiesAnimal studiesNeuroimagingModulating agentsHereditary componentChapter 40 Tourette syndrome
Fasching L, Brady M, Bloch M, Lombroso P, Vaccarino F. Chapter 40 Tourette syndrome. 2020, 675-686. DOI: 10.1016/b978-0-12-813866-3.00040-0.ChaptersConceptsTourette syndromeThalamic-cortical circuitryHuman postmortem brain tissueThalamo-cortical circuitryAdult TS patientsStriatal volume lossPostmortem brain tissueEnvironmental risk factorsStriatal interneuronsDopaminergic receptorsRecurrence rateAmeliorate symptomsBasal gangliaRisk factorsFamilial recurrence ratePharmacological strategiesVocal ticsTS patientsAnimal modelsMetabolic hypofunctionComplex neuropsychiatric disorderBrain tissueMolecular abnormalitiesNeuropsychiatric disordersGenetic alterations
2018
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2018, 5188-5203. DOI: 10.1007/978-3-319-67199-4_630.Peer-Reviewed Original Research
2016
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2016, 1-16. DOI: 10.1007/978-1-4614-6438-9_630-1.Peer-Reviewed Original Research
2015
ChemInform Abstract: Synthesis of Benzopentathiepin Analogues and Their Evaluation as Inhibitors of the Phosphatase STEP.
Baguley T, Nairn A, Lombroso P, Ellman J. ChemInform Abstract: Synthesis of Benzopentathiepin Analogues and Their Evaluation as Inhibitors of the Phosphatase STEP. ChemInform 2015, 46: no-no. DOI: 10.1002/chin.201526245.Peer-Reviewed Original ResearchChapter 106 Obsessive–Compulsive Disorder
Bloch M, Lennington J, Szuhay G, Lombroso P. Chapter 106 Obsessive–Compulsive Disorder. 2015, 1301-1310. DOI: 10.1016/b978-0-12-410529-4.00106-6.Peer-Reviewed Original ResearchCitationsConceptsObsessive-compulsive disorderEvidence-based treatmentsTreatment-refractory obsessive-compulsive disorderSignificant hereditary componentRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationThalamo-cortical circuitsMagnetic stimulationCortico-striatoSelective serotonin reuptake inhibitorsPharmacological treatment strategiesSerotonin reuptake inhibitorsAntipsychotic augmentationGenetic risk factorsReuptake inhibitorsDisordersRisk factorsTreatment strategiesAnimal studiesModulating agentsNeuroimagingHereditary componentCompulsionDeep brainObsessionChapter 107 Tourette Syndrome
Lennington J, Bloch M, Scahill L, Szuhay G, Lombroso P, Vaccarino F. Chapter 107 Tourette Syndrome. 2015, 1311-1320. DOI: 10.1016/b978-0-12-410529-4.00107-8.ChaptersCitationsConceptsTourette syndromeThalamic-cortical circuitryChildhood-onset neuropsychiatric disorderBasal ganglia circuitryStriatal interneuronsAmeliorate symptomsBasal gangliaPharmacological strategiesVocal ticsAnimal modelsPostmortem tissueNeuropsychiatric disordersSyndromeContemporary treatmentHeterogeneous disorderLarge genome-wide association studiesRecent screeningDysfunctionPotential target sitesStereotypic behaviorDisordersGenome-wide association studiesAssociation studiesChemical disruptionDopaminergic
2014
Correction to Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase
Baguley T, Xu H, Chatterjee M, Nairn A, Lombroso P, Ellman J. Correction to Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase. Journal Of Medicinal Chemistry 2014, 57: 10564-10564. PMCID: PMC4364512, DOI: 10.1021/jm5018847.Peer-Reviewed Original ResearchCitationsAltmetricInhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLOS Biology 2014, 12: e1001923. PMID: 25093460, PMCID: PMC4122355, DOI: 10.1371/journal.pbio.1001923.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsMeSH KeywordsAlzheimer DiseaseAmino Acid SequenceAnimalsBenzothiepinsCatalytic DomainCell DeathCerebral CortexCognition DisordersCysteineDisease Models, AnimalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronsPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsInhibitors of stepsSpecificity of inhibitorsIsoxazolepropionic acid receptor (AMPAR) traffickingCatalytic cysteinePTP inhibitorsTyrosine phosphataseTyrosine phosphorylationSecondary assaysSTEP KO miceReceptor traffickingFirst large-scale effortN-methyl-D-aspartate receptorsPyk2 activitySTEP inhibitorLarge-scale effortsNovel therapeutic targetSynaptic functionAlzheimer's diseaseNeurodegenerative disordersCortical cellsTherapeutic targetERK1/2Specificity experimentsPhosphataseInhibitors
2013
Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia
Deb I, Manhas N, Poddar R, Rajagopal S, Allan AM, Lombroso PJ, Rosenberg GA, Candelario-Jalil E, Paul S. Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia. Journal Of Neuroscience 2013, 33: 17814-17826. PMID: 24198371, PMCID: PMC3818554, DOI: 10.1523/jneurosci.2346-12.2013.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIschemic brain damageStriatal-enriched phosphataseBrain damageNeuroprotective roleBrain injuryP38 MAPK activationSustained p38 MAPK activationIschemic brain injuryFocal cerebral ischemiaOnset of reperfusionHypoxia-reoxygenation injuryP38 MAPKMAPK activationIschemic strokeNeurological deficitsCerebral ischemiaStroke therapyKO miceRat modelP38 MAPK pathwayCultured neuronsNeuronal culturesGenetic deletionSecondary activationInjury
Academic Achievements and Community Involvement
honor NARSAD Distinguished Investigator Award
UnknownNARSADDetails07/01/2006United States
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Child Study Center
PO Box 207900, 230 South Frontage Road
New Haven, CT 06520-7900
United States