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Stephen J. Crocker, PhDAssociate Professor, NeuroscienceCo-Associate Director, Neuroscience Graduate Program
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- Education & Training
- Committees & Organizations
- Research
- Research Opportunities
- Lab Rotations
- Publications
Education
Post-Graduate Training
Awards
| Degree | Institution | Major |
|---|---|---|
| BSc | University of King's College | Biology |
| PhD | University of Ottawa | Pharmacology |
| Postdoc | Ottawa Hospital Research Institute | Neurodegeneration |
| Postdoc | The Scripps Research Institute | Neuropharmacology |
| Postdoc | The Scripps Research Institute | Immunology |
Post-Graduate Training
| Training | Institution | Specialty |
|---|---|---|
| Fellowship | Ontario Neurotrauma Foundation | Postdoctoral Fellowship |
| Fellowship | National Multiple Sclerosis | Advanced Postdoctoral Fellowship |
| Postdoctoral | Neuroscience Research Institute | Neuroscience |
| Postdoctoral | The Scripps Research Institute | Neuropharmacology |
| Postdoctoral | The Scripps Research Institute | Immunology |
Awards
| Name of Award/Honor | Awarding Organization |
|---|---|
| Osborn Award for Excellence in Graduate Teaching in Biomedical Science | The Graduate School, UConn Health |
| National Multiple Sclerosis Society Career Transition Award (2007-2011) | National Multiple Sclerosis Society |
| Dale McFarlin Travel Award | National Multiple Sclerosis Society |
| International Outstanding Young Investigator Award | ICCP |
| Bronze Medal | Ottawa Life Sciences Conference |
| Jock Cleghorn Award. | Canadian College of Neuropsychopharmacology (CCNP) |
| Summer Studentship | Parkinson’s Disease Foundation |
| Name & Description | Category | Role | Type | Scope | Start Year | End Year |
|---|---|---|---|---|---|---|
| NIH Study Section - Standing Member Cellular and Molecular Biology of Glia (CMBG) Study Section. 3 year appointment | Study Section | Standing Member | External | National | 2023 | 2026 |
| Congressionally Directed Medical Research Fund (CDMRF) Study Panel for research on Multiple Sclerosis (a.k.a. "DoD") | Study Section | Chair | External | International | 2022 | |
| Animal Services Advisory Committee | Advisory Committee | Chair | UConn Health | University | 2022 | |
| National Multiple Sclerosis Society Biomedical Research Committee A | Study Section | Chair | External | International | 2021 | 2022 |
| Student Behavioral Health Committee | Education Committee | Member | UConn Health | University | 2021 | |
| Neuroscience Graduate Program | Education Committee | Director | UConn Health | University | 2020 | |
| Medical School Admissions Committee | Advisory Committee | Committee Member/Reviewer | UConn Health | University | 2019 | |
| Graduate Programs Committee | Education Committee | Member - Neuroscience AoC Representative | UConn Health | Local | 2018 | |
| Health Center Faculty Review Board | Advisory Committee | Member | UConn Health | Local | 2018 | 2022 |
| Journal of Neuroscience Research | Professional/Scientific Journal | Associate Editor | External | International | 2018 | 2022 |
| Curriculum Committee - UCHC Graduate School | Education Committee | Member | UConn Health | University | 2018 | |
| Neurochemistry International | Editorial Board | Editorial Advisory Board Member | External | International | 2017 | 2022 |
| Institutional Animal Care and Use Committee (IACUC) | Other | Chair | UConn Health | Local | 2016 | 2025 |
| Government Relations Committee (GRC) NMSS | Community Service | Member | External | State | 2016 | 2025 |
| Representative of Connecticut at National Multiple Sclerosis Public Policy Conference | Community Service | Member/Representative | External | National | 2016 | |
| American Association of Neuropathologists | Professional/Scientific Organization | Member | External | National | 2005 | |
| American Society of Neurochemistry | Professional/Scientific Organization | Member | External | National | 2003 | |
| Society for Neuroscience | Professional/Scientific Organization | Member | External | National | 1999 |
My lab is interested in how the immune and nervous systems interact and how this balance is disrupted by disease.
Specifically, my research program has centered around the role of glia in the context of immunity and myelin physiology during development and disease. Several recent studies provide an overview of current research projects in my lab, namely understanding human disease using induced pluripotent stem cells a a disease model (Nicaise et al. 2019 Proc. Natl. Acad. Sci USA), exploring the function of extracellular vesicles in CNS pathophysiology (Willis et al. 2020 Sci Rep; Willis et al. 2019 Proc. Natl. Acad Sci. USA).
We have several projects now exploring the role of cellular senescence, a process associated with aging, on myelin and remyelination in models of multiple sclerosis.
We also also actively studying the contributions of glia and immune cell types to a genetic demyelinating disease, Globoid cell leukodystrophy (Krabbe disease), with a focus on the role of CD8 T cells. We have determined that this fatal genetic disease elicits a profound yet previously undescribed neuroimmunological component, which could lead to novel treatment options for GLD patients.
Most of our studies are translational as we seek to identify fundamental processes related to glial functions and how these may impact the disease and physiology. For instance, we have an active project examining how CNS myelin controls bladder function as the vast majority of MS patients suffer from incontinence and bladder infections are a leading cause of hospitalization in this patient population.
There are research opportunities to study and learn about our projects (as described above), for PhD, MS, MD and MD/PhD candidates.
Accepting Lab Rotation Students: Spring 1 and 2 Block 2025
Journal Articles
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TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis acting on infiltrating CD8+ T cells.
Cancer discovery 2024 Oct;
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C1ql1 expression in oligodendrocyte progenitor cells promotes oligodendrocyte differentiation.
The FEBS journal 2024 Sep;
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Astrocytic TIMP-1 regulates production of Anastellin, an inhibitor of oligodendrocyte differentiation and FTY720 responses.
Proceedings of the National Academy of Sciences of the United States of America 2024 Jan;121(5):e2306816121
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CD8+ T cell depletion prevents neuropathology in a mouse model of globoid cell leukodystrophy.
The Journal of experimental medicine 2023 Sep;220(9):
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Cuprizone-mediated demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex.
Journal of neuroscience research 2022 May;
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Lipidomic analysis identifies age-disease-related changes and potential new biomarkers in brain-derived extracellular vesicles from metachromatic leukodystrophy mice.
Lipids in health and disease 2022 Mar;21(1):32
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Distinct profiles of cellular senescence-associated gene expression in the aged, diseased or injured central nervous system.
Neuroscience letters 2022 Feb;772136480
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The Cellular Senescence Factor Extracellular HMGB1 Directly Inhibits Oligodendrocyte Progenitor Cell Differentiation and Impairs CNS Remyelination.
Frontiers in cellular neuroscience 2022 Jan;16833186
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The Pathogenic Sphingolipid Psychosine is Secreted in Extracellular Vesicles in the Brain of a Mouse Model of Krabbe Disease.
ASN neuro 2022 Jan;1417590914221087817
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Extracellular matrix influences astrocytic extracellular vesicle function in wound repair.
Brain research 2021 Jul;1763147462
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Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease.
Molecular therapy : the journal of the American Society of Gene Therapy 2021 Jan;
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Mesenchyme-specific loss of Dot1L histone methyltransferase leads to skeletal dysplasia phenotype in mice.
Bone 2021 Jan;142115677
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Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age.
Scientific reports 2020 Jan;10(1):828
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Targeted Complement Inhibition at Synapses Prevents Microglial Synaptic Engulfment and Synapse Loss in Demyelinating Disease.
Immunity 2020 Jan;
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The Effects of IL-1β on Astrocytes are Conveyed by Extracellular Vesicles and Influenced by Age.
Neurochemical research 2020 Jan;
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Stem Cells of the Aging Brain.
Frontiers in aging neuroscience 2020 Jan;12247
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Systemic TLR2 tolerance enhances central nervous system remyelination.
Journal of neuroinflammation 2019 Jul;16(1):158
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Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis.
Proceedings of the National Academy of Sciences of the United States of America 2019 May;116(21):10488-10493
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Cellular senescence in progenitor cells contributes to diminished remyelination potential in progressive multiple sclerosis.
Proceedings of the National Academy of Sciences of the United States of America 2019 Mar;
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TIMP-1 Attenuates the Development of Inflammatory Pain Through MMP-Dependent and Receptor-Mediated Cell Signaling Mechanisms.
Frontiers in molecular neuroscience 2019 Jan;
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TIMP-1 Promotes Oligodendrocyte Differentiation Through Receptor-Mediated Signaling.
Molecular neurobiology 2018 Aug;
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Long-Term Improvement of Neurological Signs and Metabolic Dysfunction in a Mouse Model of Krabbe's Disease after Global Gene Therapy.
Molecular therapy : the journal of the American Society of Gene Therapy 2018 Jan;26874-889
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A Refined Bead-Free Method to Identify Astrocytic Exosomes in Primary Glial Cultures and Blood Plasma.
Frontiers in neuroscience 2017 Jan;11335
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iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response.
Experimental neurology 2016 Nov;288114-121
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TIMP-1 couples RhoK activation to IL-1β-induced astrocyte responses.
Neuroscience letters 2015 Oct;609165-170
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Extracellular matrix composition determines astrocyte responses to mechanical and inflammatory stimuli.
Neuroscience letters 2015 Jun;600104-9
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Aberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.
Journal of neuropathology and experimental neurology 2014 Sep;73(10):964-74
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Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis.
Stem cell reports 2014 Jul;3(1):115-30
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An in vitro model for the study of cellular pathophysiology in globoid cell leukodystrophy.
Journal of visualized experiments : JoVE 2014 Jan;(92):e51903
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MMP-3 mediates psychosine-induced globoid cell formation: implications for leukodystrophy pathology.
Glia 2013 May;61(5):765-77
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An alternate perspective on the roles of TIMPs and MMPs in pathology.
The American journal of pathology 2012 Jan;180(1):12-6
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Stomatin inhibits pannexin-1-mediated whole-cell currents by interacting with its carboxyl terminal.
PloS one 2012 Jan;7(6):e39489
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Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination.
Neuropathology and applied neurobiology 2011 Oct;37(6):643-53
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Coxsackievirus preferentially replicates and induces cytopathic effects in undifferentiated neural progenitor cells.
Journal of virology 2011 Jun;85(12):5718-32
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Astrocytic tissue inhibitor of metalloproteinase-1 (TIMP-1) promotes oligodendrocyte differentiation and enhances CNS myelination.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2011 Apr;31(16):6247-54
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A dual role for microglia in promoting tissue inhibitor of metalloproteinase (TIMP) expression in glial cells in response to neuroinflammatory stimuli.
Journal of neuroinflammation 2011 Jan;861
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How factors secreted from astrocytes impact myelin repair.
Journal of neuroscience research 2011 Jan;89(1):13-21
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Viral persistence and chronic immunopathology in the adult central nervous system following Coxsackievirus infection during the neonatal period.
Journal of virology 2009 Sep;83(18):9356-69
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Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis.
Autophagy 2009 Feb;5(2):152-8
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Effects of calpain inhibition on dopaminergic markers and motor function following intrastriatal 6-hydroxydopamine administration in rats.
Neuroscience 2009 Jan;158(2):558-69
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A novel method to establish microglia-free astrocyte cultures: comparison of matrix metalloproteinase expression profiles in pure cultures of astrocytes and microglia.
Glia 2008 Aug;56(11):1187-98
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Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination.
Multiple sclerosis (Houndmills, Basingstoke, England) 2008 Jun;14(5):577-94
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Amelioration of coxsackievirus B3-mediated myocarditis by inhibition of tissue inhibitors of matrix metalloproteinase-1.
The American journal of pathology 2007 Dec;171(6):1762-73
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Myelin oligodendrocyte glycoprotein peptide-induced experimental allergic encephalomyelitis and T cell responses are unaffected by immunoproteasome deficiency.
Journal of neuroimmunology 2007 Dec;192(1-2):124-33
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Fibronectin- and vitronectin-induced microglial activation and matrix metalloproteinase-9 expression is mediated by integrins alpha5beta1 and alphavbeta5.
Journal of immunology (Baltimore, Md. : 1950) 2007 Jun;178(12):8158-67
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Persistent macrophage/microglial activation and myelin disruption after experimental autoimmune encephalomyelitis in tissue inhibitor of metalloproteinase-1-deficient mice.
The American journal of pathology 2006 Dec;169(6):2104-16
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Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells.
Journal of neurochemistry 2006 Aug;98(3):812-23
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Regulation of axotomy-induced dopaminergic neuron death and c-Jun phosphorylation by targeted inhibition of cdc42 or mixed lineage kinase.
Journal of neurochemistry 2006 Jan;96(2):489-99
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BAG5 inhibits parkin and enhances dopaminergic neuron degeneration.
Neuron 2004 Dec;44(6):931-45
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Regulation of dopaminergic loss by Fas in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2004 Feb;24(8):2045-53
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The TIMPs tango with MMPs and more in the central nervous system.
Journal of neuroscience research 2004 Jan;75(1):1-11
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Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease.
Proceedings of the National Academy of Sciences of the United States of America 2003 Nov;100(23):13650-5
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Inhibition of calpains prevents neuronal and behavioral deficits in an MPTP mouse model of Parkinson's disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience 2003 May;23(10):4081-91
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Attenuation of MPTP-induced neurotoxicity and behavioural impairment in NSE-XIAP transgenic mice.
Neurobiology of disease 2003 Mar;12(2):150-61
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Endogenous expression of inhibitor of apoptosis proteins in facial motoneurons of neonatal and adult rats following axotomy.
Neuroscience 2003 Jan;117(3):567-75
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c-Jun mediates axotomy-induced dopamine neuron death in vivo.
Proceedings of the National Academy of Sciences of the United States of America 2001 Nov;98(23):13385-90
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NAIP protects the nigrostriatal dopamine pathway in an intrastriatal 6-OHDA rat model of Parkinson's disease.
The European journal of neuroscience 2001 Jul;14(2):391-400
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Neuroprotection by the inhibition of apoptosis.
Brain pathology (Zurich, Switzerland) 2000 Apr;10(2):283-92
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Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus.
The Journal of neuroscience : the official journal of the Society for Neuroscience 1999 Jun;19(12):5026-33
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D1-Receptor-related priming is attenuated by antisense-meditated 'knockdown' of fosB expression.
Brain research. Molecular brain research 1998 Jan;53(1-2):69-77
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Elevation of neuronal expression of NAIP reduces ischemic damage in the rat hippocampus.
Nature medicine 1997 Sep;3(9):997-1004
Reviews
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Emerging Role of Astrocyte-Derived Extracellular Vesicles as Active Participants in CNS Neuroimmune Responses.
Immunological investigations 2023 Nov;1-14
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Glia as antigen-presenting cells in the central nervous system.
Current opinion in neurobiology 2022 Dec;77102646
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Therapeutic opportunities for targeting cellular senescence in progressive multiple sclerosis.
Current opinion in pharmacology 2022 Feb;63102184
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Astrocyte-Derived Extracellular Vesicles (ADEVs): Deciphering their Influences in Aging.
Aging and disease 2021 Sep;12(6):1462-1475
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A microglial hypothesis of globoid cell leukodystrophy pathology.
Journal of neuroscience research 2016 Nov;94(11):1049-61
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Transition from identity to bioactivity-guided proteomics for biomarker discovery with focus on the PF2D platform.
Proteomics. Clinical applications 2016 Jan;10(1):8-24