ABC Transporters in Human Disease and Multidrug Resistance
ABC Transporters in Human Disease and Multidrug Resistance
批准号:
7732898
负责人:
MICHAEL DEAN
金额:
$77.22万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
ABCC1 geneABCG2 geneATP phosphohydrolaseATP-Binding Cassette TransportersAnimal ModelAntibodiesArthropodsBindingBiological ModelsCarrier ProteinsCell membraneCellsCellular biologyClassCodeComplementComplexCrustaceaDaphniaDefectDevelopmentDiseaseDrug resistanceEcologyEvolutionFailureGene FamilyGenesGenetic PolymorphismGoalsHereditary DiseaseIn VitroInsectaInvertebratesLifeMarinesMulti-Drug ResistanceMusMutateMutationNumbersOrganismOrthologous GenePatientsPharmaceutical PreparationsPoriferaProtein OverexpressionProteinsPseudoxanthoma ElasticumPumpResistanceSea UrchinsStem cellsStructure-Activity RelationshipStudy of serumTissuesToxinUrineYeastscancer stem cellcancer therapychemotherapygene functiongenome sequencinghuman diseaseinhibitor/antagonistmalemelanomametabolomicsresistance factorstumor
中文摘要
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英文摘要
The transport of molecules into and out of the cell is one of the most critical functions of living organisms. A large reason for the failure of chemotherapy in many cases is drug resistance. Pumps that remove toxins from cells are critically important in the resistance of tumors. In addition a number of genetic diseases are caused by defects in transport proteins. The ATP-binding cassette (ABC) gene family codes for transporter proteins pumping a variety of compounds across the membranes of cells and tissues. Overexpression of ABC transporters is an important cause of multidrug resistance to chemotherapy agents and these genes are mutated in diverse human diseases. ABC genes in cancer stem cells Several ABC genes are expressed in cancer stem cells allowing for an innate resistance to cancer therapy. ABCG2 is an important drug resistance gene and we have screened for and identified new inhibitors to the protein encoded by this gene. One of these is a new class of compounds known as botrylamides. The botrylamides are found in marine sponges and are simple enough chemically that derivatives can be synthesized and a structure/function relationship determined. ABCG2 is an important marker and resistance factor in cancer stem cells. Several of these compounds can be shown to inhibit substrate binding and/or ATPase activity of the protein. The ABCB5 gene, that we identified over 10 years ago has been shown to be a marker for melanoma stem cells. We are developing antibodies against this protein and are expressing the protein in culture to further study its function. Metabolomics to study ABC gene Function To understand the function of the ABCC6 gene causing pseudoxanthoma elasticum we have initiated a metabolomics study. Urine from male patients has been used to generate metabolite profiles. We have also initiated studies of serum and urine from Abcc6 -/- mice and from yeast cell deficient in an ABCC subfamily gene. These studies should aid us in identifying the substrate of this transporter. The complete complement of ABC genes was characterized in the sea urchin, a major model organism for development and cell biology. Animal models We find that the sea urchin has a dramatically expanded complement of drug transporter genes as well as orthologs of many human disease genes. In addition we have characterized the complement of ABC genes in the planktic crustacean Daphnia a globally distributed organism of central importance for the ecology of lakes and ponds. Daphnia is not only the first crustacean, but also the first non-insect arthropod to have its genome sequence determined.
期刊论文(21)
专著(0)
科研奖励(0)
会议论文
DOI:
--
发表时间:
1999
期刊:
Cancer research
影响因子:
11.2
作者:
[K. Miyake;L. Mickley;T. Litman;Z. Zhan;R. Robey;Barbara Cristensen;Mariafiorella Brangi;L. Greenberger-L.]
通讯作者:
K. Miyake;L. Mickley;T. Litman;Z. Zhan;R. Robey;Barbara Cristensen;Mariafiorella Brangi;L. Greenberger-L.
The ABCR gene in recessive and dominant Stargardt diseases: a genetic pathway in macular degeneration.
隐性和显性 Stargardt 疾病中的 ABCR 基因:黄斑变性的遗传途径。
DOI:
10.1006/geno.1999.5896
发表时间:
1999
期刊:
Genomics
影响因子:
4.4
作者:
[Zhang,K, Kniazeva,M, Hutchinson,A, Han,M, Dean,M, Allikmets,R]
通讯作者:
Allikmets,R
What can we learn about age-related macular degeneration from other retinal diseases?
关于年龄相关性黄斑变性,我们可以从其他视网膜疾病中了解到什么?
DOI:
--
发表时间:
1999
期刊:
Molecular vision
影响因子:
2.2
作者:
[Zack,DJ, Dean,M, Molday,RS, Nathans,J, Redmond,TM, Stone,EM, Swaroop,A, Valle,D, Weber,BH]
通讯作者:
Weber,BH
ABC Transporters in Human Disease & Multidrug Resistance
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批准号:6950131
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
CANCER AND INFLAMMATION: FUNCTION AND THERAPY
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批准号:8553090
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项目类别:
-
资助金额:$87.94万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Identification of Single Nucleotide Polymorphisms in Can
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批准号:7038612
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
ABC Transporters in Human Disease and Multidrug Resistan
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批准号:7038634
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Laboratory of Translational Genomics
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批准号:9339178
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项目类别:
-
资助金额:$614.56万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
CANCER AND INFLAMMATION GENETICS
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批准号:8938046
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项目类别:
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资助金额:$121.7万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
ABC Transporters in Human Disease and Multidrug Resistan
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批准号:7289915
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
ABC Transporters in Human Disease and Multidrug Resistance
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批准号:6433056
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Single Nucleotide Polymorphisms in Cancer Related Genes
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批准号:6558943
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Cancer and Inflammation - Genetics and Function
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批准号:7965062
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项目类别:
-
资助金额:$70.18万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
CANCER AND INFLAMMATION GENETICS
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批准号:8763440
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项目类别:
-
资助金额:$74.98万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
IDENTIFICATION OF SINGLE NUCLEOTIDE POLYMORPHISMS IN CANCER-RELATED GENES
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批准号:6289136
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Identification of Single Nucleotide Polymorphisms in Cancer-Related Genes
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批准号:6433048
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Complex Human Diseases - From Gene to Function to Therapy
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批准号:7965072
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项目类别:
-
资助金额:$70.18万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Identification of Single Nucleotide Polymorphisms in Can
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批准号:7337754
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
CANCER AND INFLAMMATION GENETICS
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批准号:8349453
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项目类别:
-
资助金额:$86.77万
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财政年份:--
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负责人:MICHAEL DEAN
-
依托单位:
CANCER AND INFLAMMATION: FUNCTION AND THERAPY
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批准号:8349454
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项目类别:
-
资助金额:$86.77万
-
财政年份:--
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负责人:MICHAEL DEAN
-
依托单位:
CANCER AND INFLAMMATION: FUNCTION AND THERAPY
-
批准号:8763441
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项目类别:
-
资助金额:$74.98万
-
财政年份:--
-
负责人:MICHAEL DEAN
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依托单位:
Identification of Single Nucleotide Polymorphisms in Can
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批准号:7289906
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位:
Identification of Single Nucleotide Polymorphisms in Cancer-Related Genes
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批准号:7732892
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项目类别:
-
资助金额:$77.22万
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财政年份:--
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负责人:MICHAEL DEAN
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依托单位: