Peter B Crino
University Of Pennsylvania
Project start date: 2003-01-01
Project end date: 2012-12-31
Sponsored Links Excellgen http://Excellgen.com
Gene Expression Analysis In Tuberous Sclerosis
Peter B Crino, Professor
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 5R01NS045021-04 from National Institute Of Neurological Disorders And Stroke IRG: ZRG1
Abstract: The tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disorder that affects the brain and results from mutations in one of two genes, TSC1, encoding hamartin, and TSC2, encoding tuberin. Neurological complications of TSC are the most disabling and include epilepsy in over 70-80% of TSC patients, as well as autism and mental retardation in half of TSC patients. These neuropsychiatric abnormalities in TSC result from the effects of cortical tubers, the characteristic brain lesions of TSC, on brain function. Tubers are developmental abnormalities of cerebral cortical cytoarchitecture (a form of cortical dysplasia) characterized histologically by disorganized cortical lamination and cells with aberrant morphologies. The prominent abnormal cell types in tubers are dysplastic neurons (DN), giant cells (GC), and abnormal astrocytes. Tubers are epileptogenic and seizures in TSC patients are often refractory to medical management despite anticonvulsant polytherapy. Surgical resection of tubers may be necessary to achieve adequate seizure control. The number of tubers present in TSC patients seems to correlate with the onset and severity of mental retardation and autism in TSC patients. The broad goal of this grant proposal is to investigate how hamartin and tuberin mutations contribute to tuber formation using 3 experimental paradigms. We will determine whether tubers form as a result of a "second hit" somatic mutation or haploinsufficency using a high resolution analysis of TSC1 and TSC2 genes in single microdissected GCs, DNs, and astrocytes. Second, we define the expression of five candidate gene and protein families that are pivotal in normal corticogenesis including cell adhesion molecules, transcription factors, growth factors, and cytoskeletal elements in single DNs, GCs, and astrocytes and then relate these changes in expression to the mutational state of these cell types. Third, the expression of the five candidate gene and protein families will be determined during distinct epochs of cortical developmental in 3 transgenic mouse strains in which tuberin or hamartin have been completely or conditionally knocked out. These experiments provide a strategy to define the molecular mechanism of tuber formation as a direct consequence of TSC gene mutations and the downstream effects on gene expression within distinct populations of cells at defined developmental timepoints.
Keywords: cerebral cortex, gene expression, gene mutation, neuropathology, tuberous sclerosis, astrocyte, cell adhesion molecule, glia, growth factor, nerve stem cell, transcription factor, dissection, gene targeting, genetically modified animal, human tissue, laboratory mouse, serial analysis of gene expression
Project start date: 2003-01-01
Project end date: 2007-12-31
5R01NS045021-04 (2006): $330832
5R01NS045021-03 (2005): $338794
5R01NS045021-02 (2004): $338794
STRUCTURAL CONSEQUENCES OF TSC GENE MUTATIONS IN BRAIN
Peter B Crino, Associate Professor
University Of Pennsylvania, 3451 Walnut Street, Philadelphia, Pa 19104
Grant 5R01NS045021-07 from National Institute Of Neurological Disorders And Stroke
Keywords: 3-D analysis; 3-dimensional analysis; 3D analysis; Address; Animal Welfare; Anterior; Architecture; Area; Astrocytes; Astrocytus; Astroglia; Astroprotein; Autism; Autism, Early Infantile; Autism, Infantile; Autistic Disorder; Basal Ganglia; Basal Nuclei; Bibliography; Biological Models; Blood Sample; Blood specimen; Brain; Brain region; Cell Nucleus; Cells; Cellular Expansion; Cellular Growth; Cerebellum; Cerebral cortex; Cognitive; Collection; Comment; Comment (PT); Comment [Publication Type]; Commentary; Commentary (PT); Common Rat Strains; Complex; Country; DISSEC; DNA; DNA Alteration; DNA Sequence; DNA mutation; Data; Dendrites; Deoxyribonucleic Acid; Detection; Development; Disease; Disorder; Dissection; Dysplasia; Ecological impact; Editorial Comment; Editorial Comment (PT); Electromagnetic, Laser; Embryo; Embryonic; Encephalon; Encephalons; Engineering / Architecture; Environment; Environmental Impact; Epilepsy; Epileptic Seizures; Epileptics; Equipment; Ethics Committees, Research; Event; Exhibits; Exons; FK506 Binding Protein 12-Rapamycin Associated Protein 1; FK506 Binding Protein 12-Rapamycin Associated Protein 2; FK506 binding protein 12-rapamycin associated protein 1, human; FKBP-Rapamycin Associated Protein; FKBP-rapamycin associated protein, human; FKBP12 Rapamycin Complex Associated Protein 1; FRAP1 protein, human; Functional RNA; GFA-Protein; GFAP; Gene Alteration; Gene Inactivation; Gene Mutation; Gene Silencing; Genes; Genetic Alteration; Genetic Change; Genetic Polymorphism; Genetic defect; Genetic mutation; Genomics; Genotype; Germ-Line Mutation; Germline Mutation; Giant Cells; Glial Fibrillary Acid Protein; Glial Fibrillary Acidic Protein; Glial Intermediate Filament Protein; Globus Pallidus; Grant; Hereditary Mutation; Human; Human, General; IACUC; IQ Deficit; IRBs; Impact, Environmental; In Vitro; Individual; Institutional Animal Care and Use Committee; Institutional Review Boards; International; Investigation; KIAA0243; Kanner`s Syndrome; Label; Lasers; Lateral; Lead; Lesion; MR Imaging; MR Tomography; MRI; Magnetic Resonance Imaging; Magnetic Resonance Imaging Scan; Mammals, Mice; Mammals, Rats; Man (Taxonomy); Man, Modern; Medial; Mediating; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; Messenger RNA; Methods; Mice; Micro RNA; MicroRNAs; Microscopic; Missense Mutation; Model System; Modeling; Models, Biologic; Molecular; Molecular Analysis; Mouse Strains; Multinucleated Giant Cells; Murine; Mus; Mutation; Mutation, Missense; NMR Imaging; NMR Tomography; Nerve Cells; Nerve Unit; Nervous System, Brain; Neural Cell; Neurocognitive; Neurocognitive Deficit; Neurocyte; Neurons; Non-Coding; Non-Coding RNA; Nonsense Mutation; Nuclear Magnetic Resonance Imaging; Nucleus; Pathology; Patients; Pb element; Phosphorylation; Play; Polykaryocytes; Polymorphism (Genetics); Polymorphism, Genetic; Principal Investigator; Programs (PT); Programs [Publication Type]; Protein Phosphorylation; Proteins; Published Comment; Purkinje Cells; Purkinje`s Corpuscles; Putamen; RAFT1 protein, human; RAPT1 protein, human; RNA, Messenger; Radiation, Laser; Rapamycin Target Protein; Rat; Rattus; Research; Research Ethics Committees; Research Resources; Research Specimen; Resected; Resources; Ribosomal Protein S6; Role; STAT3; STAT3 gene; Sampling; Seizure Disorder; Sequence Alteration; Somatic Mutation; Specimen; Structure; Structure of putamen; Synapsins; Syncytium; System; System, LOINC Axis 4; TSC1; TSC1 gene; TSC1/2; TSC1/2 gene; TSC1/TSC2; TSC2; TSC2 Gene Inactivation; TSC2 Tumor-Suppressor Gene Inactivation; TSC2 gene; TSC2/TSC1; Testing; Thalamic structure; Thalamus; Three-dimensional analysis; Time; Translational Regulation; Tsc1 [{C0694894}]; Tuberous sclerosis protein complex; Vertebrate Animals; Vertebrates; Viewpoint; Viewpoint (PT); Work; Zeugmatography; ing; brain control; cell growth; cerebellar Purkinje cell; cohort; disability; disease/disorder; dyscrasia; epilepsia; epileptiform; epileptogenic; experiment; experimental research; experimental study; expiration; gene function; gene product; genome mutation; heavy metal Pb; heavy metal lead; human FRAP1 protein; human subject; interest; mRNA; mTOR; miRNA; mind control; neocortical; neuronal; pallidum; polymorphism; precursor cell; programs; protein expression; putamen; rapamycin and FKBP12 target 1 protein, human; research study; response; shRNA; short hairpin RNA; small hairpin RNA; social role; substantia alba; thalamic; tuberous sclerosis complex; vertebrata; white matter
Project start date: 2003-01-01
Project end date: 2012-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
PFA/PA: PAS-07-190
5R01NS045021-07 (2010): $306977
Grants awarded to Peter B Crino
Molecular Pathogenesis Of Focal Cortical Dysplasias
Peter B Crino, Professor
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 5R01NS048557-02 from National Institute Of Neurological Disorders And Stroke IRG: DBD
Abstract: Malformations of cortical development (MOD) are the most common cause of intractable epilepsy in children. Focal cortical dysplasia (FCD) and hemimegalencephaly (HMEG) affect restricted brain regions. FCD and HMEG are sporadic disorders and have no identified cause. FCD and HMEG share similar histological features including cells exhibiting cytomegaly and abnormal morphology called balloon cells (BCs). We have shown that there is cell selective activation of the PI3K-AKT-TOR-p70S6kinase-ribosomal S6 pathway in FCD and HMEG as evidenced by expression of phosphorylated ribosomal S6 protein (phospho-S6) only in BCs. We have also identified increased activity of the Wnt/beta-catenin pathway in FCD and HMEG. We propose that FCD and HMEG result from related pathogenic mechanisms and that BCs are specifically generated by somatic gene mutations leading to activation of PI3K-AKT-TOR- p70S6kinase-ribosomal S6 or Wnt/beta-catenin cascades. To test this hypothesis, we will first demonstrate immunohistochemically that the PI3K-AKT-TOR-p70S6kinase-ribosomal S6 and Wnt/beta-catenin cascades are activated in BCs compared with cytomegalic neurons and astrocytes in FCD and HMEG. Second, we will use single cell gene expression analysis to identify altered expression of candidate genes that modulate the TOR and Wnt pathways as well as to investigate other candidate gene pathways that may contribute to increased cell size in FCD and HMEG. Third, we will use 4 mutation analysis strategies to define whole gene, multi-exon, single exon, or point mutations that may be causative in FCD and HMEG. Single nucleotide polymorphism (SNP) array analysis will permit a whole genome approach to define candidate gene loci. Loss of heterozygosity and multiplex-ligation dependent probe analysis (MLPA) assays will detect whole gene and exonic deletions. We have developed a technique to sequence genes from cDNA isolated from single microdissected cells or from genomic DNA isolated from pooled cells so that we can directly sequence at least 20 candidate genes that modulate the PI3K-AKT-TOR-p70S6kinase-ribosomal S6 and Wnt/beta-catenin pathways. These studies provide a targeted, pathway directed strategy to identify altered protein expression, gene transcription, and gene sequence that lead to the formation of FCD and HMEG during brain development.
Keywords: gene, antibody, astrocyte, brain, cell, cell cycle, cell membrane, cell morphology, cell proliferation, cell sorting, children, choice, computer, cyclin, emotion, epilepsy, gene expression, gene mutation, gene targeting, genome, glycogen synthase, high throughput technology, human, insight, lead, loss of heterozygosity, membrane, mitogen activated protein kinase, morphology, neuron, nucleotide, phosphorylation, play, point mutation, protein, protein isoform, receptor, ribosomal protein, role, sectioning, single nucleotide polymorphism, tissue, clinical research
Project start date: 2006-01-01
Project end date: 2010-12-31
5R01NS048557-02 (2007): $240869
1R01NS048557-01A2 (2006): $248063
Cellular Proliferation And Epileptogenesis
Peter B Crino, Professor
University Of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
Grant 5R21NS042334-03 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: Epilepsy is a neurologic disorder that effects between 1-4% of the population and is associated with significant morbidity and even mortality. The birth of new neurons and astrocytes (cellular proliferation) is a unique and central pathologic process that occurs in the hippocampus of patients with epilepsy that likely contributes to epileptogenesis and may be accentuated by recurrent seizures. The genes that regulate cell proliferation in epilepsy have not been identified and understanding why cell proliferation occurs in epilepsy will yield insight into seizure initiation in select patients. Indeed, the molecular pharmacologic phenotype of new cells may be distinct from existing hippocampal astrocytes and neurons ad thus, may provide critical changes in receptor or ion channel expression that fosters seizure initiation. Thus, one term goal of the proposed studies is to identify select cell populations in epilepsy that can be targeted for cell specific therapeutic modulation. The objective of this proposal is to study the molecular basis of neuronal and glial proliferation in human epilepsy and to define the molecular pharmacologic phenotype of newly born neurons and astrocytes. The goals of our proposal match well with the mission statement of the RFA and provide an intensive plan to investigate the mechanisms that modulate cellular proliferation in epilepsy. To accomplish these goals, we will assay cellular proliferation in a well-characterized rodent seizure model system and then in human epilepsy samples. The experiments in the proposal will 1) identify select populations of newly divided neurons and astrocytes in the dentate gyrus by BrdU and immunohistochemical approaches, 2) determine the electrophysiologic properties of these proliferating cells so they can be readily identified in human epilepsy samples, 3) use a targeted strategy to define altered expression of several candidate gene families in experimental and human epilepsy, and 4) corroborate the changes in gene expression with protein assays including Western analysis and immunohistochemistry.
Keywords: dentate gyrus, developmental neurobiology, generalized seizure, neurogenesis, astrocyte, cell proliferation, developmental genetics, gene expression, granule cell, neurogenetics, neuron, neurotoxicology, pilocarpine, laboratory rat, voltage /patch clamp, western blotting
Project start date: 2002-03-20
Project end date: 2005-02-28
5R21NS042334-03 (2004): $166184
DEVELOPMENTAL PATHOGENESIS OF HUMAN CORTICAL DYSPLASIA
Peter B Crino, Professor
Neurologyuniversity Of Pennsylvania
3451 Walnut Street
philadelphia, Pa 19104
Grant 5K08MH001658-03 from National Institute Of Mental Health IRG: ZRG1
Abstract: applicant´s ) Human focal cortical dysplasia (FCD) is a developmental brain malformation characterized histologically by disorganized cerebral cortical cytoarchitecture and lamination. FCD is associated with several mental disorders including mental retardation (MR) and autism. FCD likely results from abnormal neuronal migration during corticoneogenesis although the molecular events that culminate in aberrant cortical lamination are unknown. Previous work has suggested that FCD neurons may have failed to terminally differentiate prior to migration since these cells express proteins, such as the intermediate filament nestin, that are typically identified in immature neuronal precursor cells. These, dysplastic neurons may not express other developmentally appropriate genes necessary to complete migration and lamination. This proposal will describe three approaches to study the developmental and molecular pathogenesis of FCD. First, expression of transcription factors, neurotrophic factors/receptors and cell adhesion molecules mRNAs will be assayed in single nestin- or MAP1B-immunolabeled cells in human FCD specimens and compared with normal cortical neurons, and neuronal precursors in the ventricular zone. Because expression of these candidate genes varies during early development and because they have been implicated in corticogenesis, coordinate change in their relative abundance will provide insights into molecular pathways altered in FCD. Second, developmentally inappropriate genes such as s nestin or MAP1B will be overexpressed in cortical slice cultures and effects on migration will be assayed. Finally, dynamic changes in gene expression will be assayed in actively migrating neurons in animal models of FCD including administration of exogenous neurotrophins or antisense oligonucleotides. It is anticipated that these studies will provide for the first time a view of altered gene expression in FCD, which will shed light on the pathogenesis of these lesions. Furthermore, in identifying alterations in specific genes, the relationship between FCD and mental disorders can be rendered. These analyses may point toward new avenues for therapy
Keywords: congenital brain disorder, developmental genetics, developmental neurobiology, molecular pathology, neuropathology cell adhesion molecule, cell differentiation, gene amplification, gene expression, genetic regulation, messenger RNA, neurofilament protein, neurotrophic factor, transcription factor antisense nucleic acid, complementary DNA, human tissue, immunocytochemistry, polymerase chain reaction, tissue /cell culture
Project start date: 1998-12-01
Project end date: 2003-11-30
5K08MH001658-03 (2001): $154238
5K08MH001658-02 (2000): $149891
1K08MH001658-01 (1999): $158670
GENE EXPRESSION AND CLONALITY IN DYSPLASTIC CORTICAL NEU
Peter B Crino, Professor
Neurologyuniversity Of Pennsylvania
3451 Walnut Street
philadelphia, Pa 19104
Grant 5R21NS039938-02 from National Institute Of Neurological Disorders And Stroke IRG: ZNS1
Abstract: Applicant´s ) Focal regions of disorganized cortical lamination and abnormal neuronal cytoarchitecture (focal cortical dysplasia, FCD) are in utero developmental brain malformations which have been identified in many neuropsychiatric disorders including mental retardation syndromes (MR), autism, and epilepsy. FCD likely results from abnormal neural migration during corticogenesis although the molecular events leading to aberrant cortical lamination in these divergent conditions are unknown. The major difficulty in addressing the molecular pathogenesis of FCD is that many epilepsy and mental retardation syndromes are of unclear inheritance pattern rendering a genetic or pedigree analysis complicated. Thus, novel strategies must be implemented to address two compelling questions regarding the pathogenesis of FCD 1) what is the phenotype of dysplastic cells and 2) what mechanisms are responsible for disorganized cortical lamination during corticogenesis. Answers to these questions will shed light on the practical question of how altered laminar and cellular cytoarchitecture in FCD contributes to the neurological manifestations such as seizures, MR, and behavioral abnormalities in such a wide variety of neurological disorders. Three sets of experiments will investigate the phenotype of dysplastic cells in human FCD specimens and assess the expression of developmentally regulated genes necessary for cortical lamination in an experimental model of FCD. Because of the heterogeneous cell types within FCD, a central feature of the proposed experiments is the use of single cell mRNA amplification technology. This novel approach permits quantification of mRNA abundance in individual immunolabeled or live neurons that are of similar or distinct phenotype. Analysis of human FCD specimens will provide a direct avenue to investigate the developmental phenotype of FCD neurons. The model FCD system will permit assessment of gene regulation during the dynamic phases of cortical migration. The overall objective of the proposal is to determine the molecular pathways that lead to disorganized cortical cytoarchitecture in FCD. Furthermore, by identifying altered expression of select genes, the relationship between FCD and various mental disorders can be discerned. These analyses may point toward new avenues for therapy
Keywords: brain disorder, cerebral cortex, epilepsy, gene expression, mental retardation cell adhesion molecule, cell migration, developmental neurobiology, disease /disorder model, growth factor receptor, messenger RNA, neurogenesis, neurogenetics, neuron, neuropathology, neuropharmacology, neurotrophic factor, transcription factor biotechnology, clinical research, human subject, immunocytochemistry, laboratory rat, northern blotting, polymerase chain reaction
Project start date: 2000-05-15
Project end date: 2003-04-30
5R21NS039938-02 (2001): $152650
1R21NS039938-01 (2000): $152650
MOLECULAR PATHOGENESIS OF FOCAL CORTICAL DYSPLASIAS
Peter B Crino, Associate Professor
University Of Pennsylvania, 3451 Walnut Street, Philadelphia, Pa 19104
Grant 5R01NS048557-05 from National Institute Of Neurological Disorders And Stroke
Keywords: 0-11 years old; Affect; Allelic Loss; Antibodies; Assay; Astrocytes; Astrocytus; Astroglia; BZS; Bioassay; Biologic Assays; Biological Assay; Body Tissues; Brain; Brain region; CTNNB1; CUL-2; Cadherin-Associated Protein, Beta; Cadherin-Associated Protein, Beta 1 (88kD); Candidate Disease Gene; Candidate Gene; Catenin, Beta-1; Cell Communication and Signaling; Cell Count; Cell Cycle; Cell Division Cycle; Cell Growth in Number; Cell Multiplication; Cell Number; Cell Proliferation; Cell Signaling; Cell Size; Cell surface; Cells; Cellular Proliferation; Child; Child Youth; Children (0-21); Chimp; Chimpanzee; Closure by Ligation; Complementary DNA; Computer Assisted; Cortical Dysplasia; Cortical Malformation; Cyclins; Cytomegalic Cell; DNA Alteration; DNA mutation; DNA, Complementary; Data; Development; Disease; Disorder; EC 2.7; Encephalon; Encephalons; Event; Exhibits; Exons; Extracellular Signal-Regulated Kinase Gene; FK506 Binding Protein 12-Rapamycin Associated Protein 1; FK506 Binding Protein 12-Rapamycin Associated Protein 2; FK506 binding protein 12-rapamycin associated protein 1, human; FKBP-Rapamycin Associated Protein; FKBP-rapamycin associated protein, human; FKBP12 Rapamycin Complex Associated Protein 1; FRAP1 protein, human; Gene Alteration; Gene Components; Gene Deletion; Gene Expression; Gene Mutation; Gene Transcription; Genes; Genetic Alteration; Genetic Change; Genetic Transcription; Genetic defect; Genetic mutation; Genome; Genomics; Glycogen Synthase Kinases; Goals; High Throughput Assay; Human; Human, Child; Human, General; IGF-1; IGF-I; IGF-I-SmC; IGF1; Individual; Insertion Mutation; Insulin-Like Growth Factor 1; Insulin-Like Growth Factor I; Insulin-Like Somatomedin Peptide I; Intracellular Communication and Signaling; Intracellular Second Messengers; Intractable Epilepsy; Isoforms; JN Kinase; JNK; JNK Mitogen-Activated Protein Kinases; JNK1; JNK1 Kinase; JNK1 protein; JNK1A2; JNK21B1/2; Kinases; Label; Lead; Ligation; Loss of Heterozygosity; MAP Kinase 8; MAP Kinase 8 Gene; MAP Kinase Gene; MAPK; MAPK8; MAPK8 Mitogen-Activated Protein Kinase; MAPK8 gene; MHAM; MMAC1; Man (Taxonomy); Man, Modern; Membrane; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase Gene; Molecular; Morphology; Mutation; Mutation Analysis; Nerve Cells; Nerve Unit; Nervous System, Brain; Neural Cell; Neurocyte; Neurons; PRKM8; PRO2286; PTEN; PTEN gene; PTEN1; Pan; Pan Genus; Pan Species; Pathogenesis; Pathway interactions; Pb element; Phosphatase and Tensin Homolog; Phosphoprotein Phosphatase; Phosphoprotein Phosphatase-2C; Phosphoprotein Phosphohydrolase; Phosphorylation; Phosphotransferases; Play; Point Mutation; Polymorphism, Single Base; Principal Investigator; Programs (PT); Programs [Publication Type]; Protein Isoforms; Protein Phosphatase C; Protein Phosphatase-1; Protein Phosphatase-2A; Protein Phosphorylation; Protein phosphatase; Proteins; RAFT1 protein, human; RAPT1 protein, human; RNA Expression; Rapamycin Target Protein; Receptor Protein; Research Specimen; Ribosomal Protein S6; Role; SAP Kinase-1; SAPK/JNK; SAPK1; SAPK1 Mitogen-Activated Protein Kinase; SAPK1/JNK; SNP; SNPs; Second Messenger Systems; Second Messengers; Sequence Alteration; Signal Transduction; Signal Transduction Systems; Signaling; Single Nucleotide Polymorphism; Somatic Mutation; Somatomedin C; Specimen; Stress-Activated Protein Kinase JNK1; Stress-Activated Protein Kinase gamma; Testing; Tissues; Transcription; Transcription Activation; Transcription Activator; Transcription Coactivator; Transcription Factor Coactivator; Transcription, Genetic; Transcriptional Activation; Transcriptional Activator; Transcriptional Activator/Coactivator; Transcriptional Coactivator; Transphosphorylases; Up-Regulation; beta catenin; biological signal transduction; brain tissue; c-jun Amino-Terminal Kinase; c-jun Kinase-1; c-jun N-Terminal Kinase; c-jun N-Terminal Kinase 1; cDNA; cDNA Arrays; cDNA Microarray; children; computer aided; disease/disorder; experiment; experimental research; experimental study; gene deletion mutation; gene function; gene product; genome mutation; genome-wide; heavy metal Pb; heavy metal lead; high throughput screening; human FRAP1 protein; in vitro Assay; insight; jun-NH2-Terminal Kinase; loss of function mutation; mTOR; malformation; membrane structure; neuronal; pathway; programs; protein expression; rapamycin and FKBP12 target 1 protein, human; receptor; research study; second messenger; selective expression; selectively expressed; social role; stress-activated protein kinase 1; youngster
Project start date: 2006-01-01
Project end date: 2010-12-31
Budget start date: 1-JAN-2010
Budget end date: 31-DEC-2010
5R01NS048557-05 (2010): $272525
Sponsored Links Excellgen http://Excellgen.com