ErbB Signaling in Liver Ontogeny and Regeneration
ErbB Signaling in Liver Ontogeny and Regeneration
批准号:
7895278
负责人:
WILLIAM E RUSSELL
金额:
$5.22万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2009
资助国家:
美国
项目状态:
已结题
起止时间:
2009-07-17 至 2012-06-30
关键词:
AdultAnimalsArtificial LiverBiological ProcessBiologyCarcinogensCell LineCell ProliferationCell TransplantationCellsChemical InjuryChemicalsComplexDataDevelopmentDifferentiation and GrowthDisseminated Malignant NeoplasmERBB2 geneEpidermal Growth FactorEpidermal Growth Factor ReceptorExcisionFamily memberGene TargetingGenerationsGenesGeneticGoalsGrantGrowthGrowth FactorHepatectomyHepatic MassHepatocyteHepatocyte Growth FactorHomologous GeneHypertrophyIn VitroKnockout MiceLaboratoriesLigandsLiverLiver RegenerationMalignant NeoplasmsMediatingMetabolicMitogensModelingMusNatural regenerationNormal tissue morphologyPharmaceutical PreparationsPhenotypePhosphorylationPlayProtein FamilyProtein Tyrosine KinaseProtein Tyrosine PhosphataseProteinsProteolytic ProcessingProto-Oncogene Protein c-metRecruitment ActivityRegulationRoleSignal TransductionSignaling MoleculeStimulation of Cell ProliferationStressSystemTestingTissuesTransducersTyrosine PhosphorylationTyrphostinsUndifferentiatedWound Healingautocrinecarcinogenesiscell motilitycombinatorialimprovedinjuredknock-downknockout animalmeetingsmigrationoval cellpolypeptidereceptorresponserestorationtumorigenesis
中文摘要
我们的长期目标是了解控制生长的机制,
英文摘要
Our long-term goal is to understand the mechanisms that control the growth,
differentiation, and regeneration of the liver. Epidermal growth factor (EGF) and its
homologs are the most thoroughly studied growth factors in the control of liver growth,
regeneration and carcinogenesis. However, the relationship of EGF to the liver is
complex, since we now know that there are multiple EGF-like molecules and that they
act through four different receptors, the ErbB proteins. Signaling by ErbB tyrosine
kinases depends on not only which ligands are present, but also which combinations of
receptors are recruited into signaling complexes. There are also negative regulators of
ErbB signaling, such as tyrosine phosphatases and proteins, such as Ralt, that complex
directly with the ErbB proteins. This analysis is also complicated by the role of other
receptors that interact with the ErbB proteins, including c-met, the receptor for HGF. We
and others have shown that c-met requires a functional EGF receptor to elicit its effects
on motility and mitogenesis. This grant focuses on the role played by the ErbB receptors
as regulators of growth and differentiation in the liver. We have created hepatocytespecific
EGFr, ErbB2, and ErbB3 deficient mice by gene targeting, and have obtained
liver-specific cMet gene deleted mice. The specific aims of this proposal are to: 1) To
define the interactions among the ErbB proteins and c-met in the mitogenic signaling of
the normal and regenerating liver; 2) To evaluate the central role of the ErbB proteins as
signal tansducers of HGF. Progress toward these aims will improve our understanding
of how EGF-like molecules signal in a normal tissue, how the liver differentiates into its
adult functional form, and how these potent mitogens regulate the dramatic restoration of
liver mass during regeneration. Liver regeneration is a paradigm for other conditions of
normal or altered growth regulation, including tissue hypertrophy, wound healing, and
cancer. In addition to elucidating the mechanisms of growth control in the liver, our
studies may ultimately aid in the generation of mature hepatocytes from undifferentiated
cells for transplantation and for the generation of artificial livers.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Hepatocyte Clock Genes in Alcohol and High Fat Diet - Induced Liver Injury
-
批准号:8512169
-
项目类别:
-
资助金额:$22.56万
-
财政年份:2014
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Hepatocyte Clock Genes in Alcohol and High Fat Diet - Induced Liver Injury
-
批准号:9293725
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项目类别:
-
资助金额:$0.36万
-
财政年份:2014
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Hepatocyte Clock Genes in Alcohol and High Fat Diet - Induced Liver Injury
-
批准号:8854000
-
项目类别:
-
资助金额:$17.73万
-
财政年份:2014
-
负责人:WILLIAM E RUSSELL
-
依托单位:
ErbB Receptor Signaling in DEN-induced Murine Hepatocarcinogenesis
-
批准号:7876518
-
项目类别:
-
资助金额:$19.72万
-
财政年份:2010
-
负责人:WILLIAM E RUSSELL
-
依托单位:
ErbB Receptor Signaling in DEN-induced Murine Hepatocarcinogenesis
-
批准号:8043654
-
项目类别:
-
资助金额:$16.43万
-
财政年份:2010
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:8913146
-
项目类别:
-
资助金额:$49.99万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:7938050
-
项目类别:
-
资助金额:$52.22万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:8074357
-
项目类别:
-
资助金额:$49.94万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:8288277
-
项目类别:
-
资助金额:$28.27万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:8468691
-
项目类别:
-
资助金额:$48.46万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:7786671
-
项目类别:
-
资助金额:$49.49万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Vanderbilt University: Clinical Center Application, Type 1 Diabetes TrialNet
-
批准号:8776482
-
项目类别:
-
资助金额:$51.57万
-
财政年份:2009
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Receptor Guanylyl Cyclases in Regenerating Liver
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批准号:7221944
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项目类别:
-
资助金额:$27.62万
-
财政年份:2003
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Receptor Guanylyl Cyclases in Regenerating Liver
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批准号:6579495
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项目类别:
-
资助金额:$32.96万
-
财政年份:2003
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Receptor Guanylyl Cyclases in Regenerating Liver
-
批准号:6911745
-
项目类别:
-
资助金额:$29.13万
-
财政年份:2003
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Receptor Guanylyl Cyclases in Regenerating Liver
-
批准号:6740845
-
项目类别:
-
资助金额:$29.13万
-
财政年份:2003
-
负责人:WILLIAM E RUSSELL
-
依托单位:
Receptor Guanylyl Cyclases in Regenerating Liver
-
批准号:7080387
-
项目类别:
-
资助金额:$28.45万
-
财政年份:2003
-
负责人:WILLIAM E RUSSELL
-
依托单位:
ErbB Signaling in Liver Ontogeny and Regeneration
-
批准号:6936675
-
项目类别:
-
资助金额:$35.06万
-
财政年份:1998
-
负责人:WILLIAM E RUSSELL
-
依托单位:
ErbB Signaling in Liver Ontogeny and Regeneration
-
批准号:7102585
-
项目类别:
-
资助金额:$34.24万
-
财政年份:1998
-
负责人:WILLIAM E RUSSELL
-
依托单位:
ErbB Signaling in Liver Ontogeny and Regeneration
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批准号:7770850
-
项目类别:
-
资助金额:$36.47万
-
财政年份:1998
-
负责人:WILLIAM E RUSSELL
-
依托单位:
海外基金