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One or more keywords matched the following properties of Carroll, Steven
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overview Dr. Steven Carroll is is Professor and Chair of the Department of Pathology and Laboratory Medicine at the Medical University of South Carolina (MUSC), where he holds the Gordon R. Hennigar, Jr., MD, Endowed Chair in Pathology. Dr. Carroll is board certified by the American Board of Pathology in Anatomic Pathology and Neuropathology. Dr. Carroll’s research program, which is funded by the National Institutes of Health, the Department of Defense and the Children’s Tumor Foundation, studies the role that the growth factor neuregulin-1 and its erbB receptors plays in the pathogenesis of neurodegenerative diseases and neurofibromatosis-associated peripheral nerve sheath tumors. Dr. Carroll serves as the Director of the South Carolina Alzheimer’s Disease Research Center at MUSC and as Director of the Carroll A. Campbell Jr. Neuropathology Laboratory (Brain Bank). Dr. Carroll also serves as Director of the Hollings Cancer Center Biorepository & Tissue Analysis Shared Resource. Dr. Carroll is an Associate Editor for the American Journal of Pathology and the Journal of Neuropathology and Experimental Neurology and is a member of the Editorial Board for Neuro-Oncology. He is a founding member of the international Down Syndrome Biobanking Consortium, which includes MUSC, the Barrow Neurological Institute, the University of Colorado Denver, the University of California Irvine, New York University, the Sant Pau Memory Unit (Barcelona, Spain), Cambridge University (UK), the Karolinska Institutet (Stockholm, Sweden) and the University of Calcutta (India). Working with the Children’s Tumor Foundation, Dr. Carroll has established a national network to bank biospecimens from autopsied patients who had neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis. In addition to these research areas, Dr. Carroll participates in the Human Cooperative Tissue Network, a multi-institution network that banks and distributes tumor tissue for research to investigators across the United States and elsewhere. The Biorepository is also an active participant in an effort headed by Dr. Marvella Ford that partners MUSC with South Carolina State University; this project focuses on understanding the basis for disparate outcomes in cancer patients from diverse backgrounds. Dr. Carroll received his B.S. degree from the University of Memphis in 1981. He then attended Baylor College of Medicine, receiving his Ph.D. in Cell Biology in 1986 and his M.D. in 1988. Dr. Carroll’s postdoctoral research fellowship, Anatomic Pathology Residency and Neuropathology Fellowship were performed at the Washington University School of Medicine (1988-1994). Prior to his arrival at MUSC, Dr. Carroll was Professor of Pathology, Neurobiology and Cell Biology at the University of Alabama at Birmingham (UAB) and the Director of the UAB Division of Neuropathology. While at UAB, Dr. Carroll served as an attending neuropathologist at the University of Alabama Hospital, the Birmingham VA, UAB Highlands Hospital and Alabama Children’s Hospital. He was a Scientist in the UAB Alzheimer’s Disease Research Center, the Mental Retardation Research Center, the Center for Aging, the Center for Glial Biology in Medicine, the Civitan International Research Center and the Center for Neurodegeneration and Experimental Therapeutics as well as being as a Member of the Comprehensive Neuroscience Center and a Senior Scientist in the UAB Comprehensive Cancer Center. Dr. Carroll is certified by the American Board of Pathology in Anatomic Pathology and Neuropathology. The Carroll laboratory focuses on identifying the abnormalities that promote the pathogenesis of cancer and neurodegenerative diseases and using this information to develop effective new therapies. We have a particular interest in the role that the growth factor neuregulin-1 (NRG1) and its erbB receptors play in the development of these diseases. Our work in cancer biology is directed towards determining how neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) develop in patients with the multi-system genetic disease neurofibromatosis type 1 (NF1) with therapeutic development being the end goal. We are pursuing a two-pronged approach to achieve this goal. In our first approach, we are using our understanding of the natural history of neurofibromas and MPNSTs to guide us to existing agents that are potentially effective against these tumors. For instance, since aberrant Ras signaling is characteristic of these tumors, we have used phosphoproteomics and other approaches to identify potential druggable targets within the pathways downstream of NF1-regulated Ras proteins as well as upstream activators of Ras in neurofibromas and MPNSTs. This latter group includes receptors for the growth factor neuregulin-1 (NRG1), which led us to create mice in which we can genetically ablate these receptors and examine the effect this has on MPNST pathogenesis. Our second, longer term approach is to identify novel therapeutic targets by comprehensively defining the genomic and epigenetic abnormalities that mediate the pathogenesis of plexiform neurofibromas and MPNSTs. To achieve this, we are using cross-species comparative oncogenomics, a method in which driver mutations are first identified in a mouse cancer model and then validated in human tumors. For these studies, we have created several genetically engineered mouse models which recapitulate the process of neurofibroma-MPNST progression seen in humans. We have performed comprehensive genomic analyses (array comparative genomic hybridization, high density SNP array analyses, whole exome sequencing and whole transcriptome sequencing) of MPNSTs from these mice, together with a reference set of human MPNST tumors and cell lines, to identify the driver mutations responsible for tumor development. We have partnered these genomic analyses with functional (genome-scale shRNA) screens to identify gene products that are essential for proliferation and survival. Ongoing work is directed towards performing preclinical trials with mouse models to test the effectiveness of drugs that target these gene products. Our work in neurobiology focuses on Alzheimer’s disease, frontotemporal dementias and amyotrophic lateral sclerosis (ALS). Our laboratory was the first to show that NRG1, a protein that plays an important role in synaptogenesis, and its receptors are aberrantly distributed in neuritic plaques in humans with Alzheimer’s disease and genetically engineered mouse models of Alzheimer’s disease. After globally identifying the cellular populations expressing erbB receptors in the adult rat brain with immunohistochemistry and in situ hybridization, we additionally showed that NRG1 plays an important role in shaping the dendritic and axonal trees of hippocampal neurons and that this growth factor is an important survival factor for motor neurons in the spinal cord. At present, we are constructing several new genetically engineered mouse models to assess the role that specific erbB mutations play in the pathogenesis of frontotemporal dementias and ALS and to ascertain whether NRG1 can be used to slow the development of Alzheimer’s disease and other dementias. As with our cancer work, we partner mouse and cell culture models of neurodegenerative diseases with studies of brain tissue and other biospecimens collected from patients with dementia. These studies are facilitated by the fact that Dr. Carroll is the Director of the Carroll A. Campbell, Jr. Neuropathology Laboratory, which contains a collection of several hundred brains from patients with Alzheimer’s and related dementias that have been donated for research. In collaboration with Drs. Eric Hamlett, Brad Schulte and Judy Dubno, we are using these specimens to determine whether pathologic changes affecting the brain circuitry responsible for hearing and other senses occurs in Alzheimer’s disease and whether clinical changes in these senses can be used as a biomarker for diagnosing the early stages of Alzheimer’s disease. As noted above, the Carroll A. Campbell, Jr. Neuropathology Laboratory is a founding member of an international consortium of brain banks that collect brain tissue and other research specimens from Down syndrome patients, who almost inevitably develop Alzheimer’s disease in their forties. In collaboration with Dr. Eric Hamlett and Lotta Granholm, we have used specimens from these patients to establish that changes in the protein cargo contained in neuronally-derived exosomes can be used as a biomarker for the early stages in the development of Alzheimer’s disease.
One or more keywords matched the following items that are connected to Carroll, Steven
Item TypeName
Concept Optic Nerve Neoplasms
Concept Receptors, Nerve Growth Factor
Concept Sciatic Nerve
Concept Nerve Fibers, Unmyelinated
Concept Spinal Nerve Roots
Concept Nerve Degeneration
Concept Nerve Sheath Neoplasms
Concept Nerve Fibers, Myelinated
Concept Nerve Growth Factor
Concept Nerve Growth Factors
Concept Receptor, Nerve Growth Factor
Concept Nerve Tissue Proteins
Academic Article Elements in the 5' flanking sequences of the mouse low-affinity NGF receptor gene direct appropriate CNS, but not PNS, expression in transgenic mice.
Academic Article Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia.
Academic Article Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration.
Academic Article Neurotrophin sensitivity of prevertebral and paravertebral rat sympathetic autonomic ganglia.
Academic Article Expression of JE (monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wld(s) mice.
Academic Article Lysophosphatidic acid promotes the proliferation of adult Schwann cells isolated from axotomized sciatic nerve.
Academic Article Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line.
Academic Article Hypertrophic neuropathies and malignant peripheral nerve sheath tumors in transgenic mice overexpressing glial growth factor beta3 in myelinating Schwann cells.
Academic Article Constitutive activation of the neuregulin-1/erbB signaling pathway promotes the proliferation of a human peripheral neuroepithelioma cell line.
Academic Article ErbB transmembrane tyrosine kinase receptors are expressed by sensory and motor neurons projecting into sciatic nerve.
Academic Article Neuregulin-1beta induces neurite extension and arborization in cultured hippocampal neurons.
Academic Article Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors. I. The role of tumor suppressor mutations.
Academic Article Tumor suppressor mutations and growth factor signaling in the pathogenesis of NF1-associated peripheral nerve sheath tumors: II. The role of dysregulated growth factor signaling.
Academic Article Activation of the neuregulin-1/ErbB signaling pathway promotes the proliferation of neoplastic Schwann cells in human malignant peripheral nerve sheath tumors.
Academic Article Neuregulin growth factors and their ErbB receptors form a potential signaling network for schwannoma tumorigenesis.
Academic Article Interactions between beta-neuregulin and neurotrophins in motor neuron apoptosis.
Academic Article Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia.
Academic Article Neuregulin-1 beta and neuregulin-1 alpha differentially affect the migration and invasion of malignant peripheral nerve sheath tumor cells.
Academic Article Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen receptor-independent manner.
Academic Article Orthotopic xenografting of human luciferase-tagged malignant peripheral nerve sheath tumor cells for in vivo testing of candidate therapeutic agents.
Academic Article Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.
Academic Article Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms.
Academic Article The pan erbB inhibitor PD168393 enhances lysosomal dysfunction-induced apoptotic death in malignant peripheral nerve sheath tumor cells.
Academic Article Transgenic mice overexpressing neuregulin-1 model neurofibroma-malignant peripheral nerve sheath tumor progression and implicate specific chromosomal copy number variations in tumorigenesis.
Academic Article Malignant peripheral nerve sheath tumor invasion requires aberrantly expressed EGF receptors and is variably enhanced by multiple EGF family ligands.
Academic Article 4-Hydroxytamoxifen induces autophagic death through K-Ras degradation.
Academic Article Neuregulin-1 overexpression and Trp53 haploinsufficiency cooperatively promote de novo malignant peripheral nerve sheath tumor pathogenesis.
Academic Article BNIP3 regulates AT101 [(-)-gossypol] induced death in malignant peripheral nerve sheath tumor cells.
Academic Article Combinatorial therapy with tamoxifen and trifluoperazine effectively inhibits malignant peripheral nerve sheath tumor growth by targeting complementary signaling cascades.
Academic Article Assessment of oncolytic HSV efficacy following increased entry-receptor expression in malignant peripheral nerve sheath tumor cell lines.
Academic Article Classic Ras Proteins Promote Proliferation and Survival via Distinct Phosphoproteome Alterations in Neurofibromin-Null Malignant Peripheral Nerve Sheath Tumor Cells.
Academic Article Correction: BNIP3 Regulates AT101 [(-)-Gossypol] Induced Death in Malignant Peripheral Nerve Sheath Tumor Cells.
Academic Article The Challenge of Cancer Genomics in Rare Nervous System Neoplasms: Malignant Peripheral Nerve Sheath Tumors as a Paradigm for Cross-Species Comparative Oncogenomics.
Academic Article STAT1 and NF-?B Inhibitors Diminish Basal Interferon-Stimulated Gene Expression and Improve the Productive Infection of Oncolytic HSV in MPNST Cells.
Academic Article BH3 mimetics suppress CXCL12 expression in human malignant peripheral nerve sheath tumor cells.
Academic Article The Molecular and Morphologic Structures That Make Saltatory Conduction Possible in Peripheral Nerve.
Academic Article Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF deprivation in utero.
Academic Article The NGFI-B protein, an inducible member of the thyroid/steroid receptor family, is rapidly modified posttranslationally.
Academic Article Usp9X Regulates Cell Death in Malignant Peripheral Nerve Sheath Tumors.
Academic Article The evolution and multi-molecular properties of NF1 cutaneous neurofibromas originating from C-fiber sensory endings and terminal Schwann cells at normal sites of sensory terminations in the skin.
Academic Article ErbB4 promotes malignant peripheral nerve sheath tumor pathogenesis via Ras-independent mechanisms.
Grant NEUREGULINS AND THE PATHOLOGY OF NERVE INJURY
Grant Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors
Grant Evaluating the role of NRG-1 receptors in MPNST tumorigenesis
Grant Novel Treatment of NF-1 Associated Malignant Peripheral Nerve Sheath Tumors
Grant Evaluation of the Effectiveness of Calmodulin Inhibitors for the Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors
Grant Malignant Peripheral Nerve Sheath Tumors' Achilles Heel: Combinatorial Targeting of ERBB3 and Calcium Signaling
Grant Engineered Herpes Siumplex Viruses for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Grant Regulation of Ras isoforms in malignant peripheral nerve sheath tumors
Grant Multi-Modal Lysosomotropic Death Therapy for Malignant Peripheral Nerve Sheath Tu
Grant The Role of HER3 and IGF1R, through Non-Classical Ras Signaling, on Malignant Peripheral Nerve Sheath Tumor Progression
Grant Comparative Oncogenomics for Peripheral Nerve Sheath Cancer Gene Discovery
Grant Role of Neuregulin-1 in Schwann Cell Neoplasia
Academic Article Independent and epistatic effects of variants in VPS10-d receptors on Alzheimer disease risk and processing of the amyloid precursor protein (APP).
Academic Article A rare mutation in UNC5C predisposes to late-onset Alzheimer's disease and increases neuronal cell death.
Academic Article Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line.
Academic Article Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells.
Academic Article LPAR1 and aberrantly expressed LPAR3 differentially promote the migration and proliferation of malignant peripheral nerve sheath tumor cells.
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