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Dolan, Mary Eileen

One or more keywords matched the following properties of Dolan, Mary Eileen

Property	Value
overview	The Dolan lab is focused on improving the quality of life of cancer patients through the identification of genetic variants associated with risk for severe and persistent toxicities following chemotherapy (i.e. peripheral neuropathy, ototoxicity, tinnitus), particularly in children and young adults whose adverse sequelae could persist throughout their lifetimes. To this end, they perform clinical genome wide association studies to identify genetic variants associated with toxicity in patients following chemotherapy and determine whether there is shared genetic architecture with idiopathic forms of these traits. They develop preclinical models to elucidate the biochemical and cellular impact of genes identified in clinical studies of chemotherapeutic toxicity. Their approach integrates multiple large datasets including: genetic variation, gene expression, miRNA, modified cytosine, transcription factor levels and chemotherapeutic induced pharmacologic traits. Her laboratory made the seminal observation that chemotherapeutic-induced cytotoxicity is a heritable trait and that pharmacologic SNPs, identified through GWAS, are enriched in expression quantitative trait loci. More recently, her laboratory has developed an induced pluripotent stem cell derived neuronal cell model to evaluate genes contributing to chemotherapeutic-induced neuropathy, a common adverse event of multiple chemotherapeutic agents. They are creating a resource of human induced pluripotent stem cell derived neurons from well-phenotyped cancer survivors following treatment with paclitaxel, vincristine or cisplatin to be used to identify an in vitro toxicity readout that parallels the clinical phenotype. The models they are developing will have broad applicability for gaining insight on druggable targets to treat or prevent this devastating side effect of chemotherapy and providing an understanding of the genetic components and genes contributing to severe toxicity.

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overview

The Dolan lab is focused on improving the quality of life of cancer patients through the identification of genetic variants associated with risk for severe and persistent toxicities following chemotherapy (i.e. peripheral neuropathy, ototoxicity, tinnitus), particularly in children and young adults whose adverse sequelae could persist throughout their lifetimes. To this end, they perform clinical genome wide association studies to identify genetic variants associated with toxicity in patients following chemotherapy and determine whether there is shared genetic architecture with idiopathic forms of these traits. They develop preclinical models to elucidate the biochemical and cellular impact of genes identified in clinical studies of chemotherapeutic toxicity. Their approach integrates multiple large datasets including: genetic variation, gene expression, miRNA, modified cytosine, transcription factor levels and chemotherapeutic induced pharmacologic traits. Her laboratory made the seminal observation that chemotherapeutic-induced cytotoxicity is a heritable trait and that pharmacologic SNPs, identified through GWAS, are enriched in expression quantitative trait loci. More recently, her laboratory has developed an induced pluripotent stem cell derived neuronal cell model to evaluate genes contributing to chemotherapeutic-induced neuropathy, a common adverse event of multiple chemotherapeutic agents. They are creating a resource of human induced pluripotent stem cell derived neurons from well-phenotyped cancer survivors following treatment with paclitaxel, vincristine or cisplatin to be used to identify an in vitro toxicity readout that parallels the clinical phenotype. The models they are developing will have broad applicability for gaining insight on druggable targets to treat or prevent this devastating side effect of chemotherapy and providing an understanding of the genetic components and genes contributing to severe toxicity.

One or more keywords matched the following items that are connected to Dolan, Mary Eileen

Item Type	Name
Concept	Breast Neoplasms
Concept	Cerebellar Neoplasms
Concept	Colonic Neoplasms
Concept	Genital Neoplasms, Female
Concept	Kidney Neoplasms
Concept	Drug Resistance
Concept	Liver Neoplasms
Concept	Ovarian Neoplasms
Concept	Lung Neoplasms
Concept	Neoplasms, Germ Cell and Embryonal
Concept	Prostatic Neoplasms
Concept	Head and Neck Neoplasms
Concept	Testicular Neoplasms
Concept	Drug Resistance, Neoplasm
Concept	Central Nervous System Neoplasms
Concept	Neoplasms, Second Primary
Concept	Nervous System Neoplasms
Concept	Neoplasms, Experimental
Concept	Neoplasms, Squamous Cell
Concept	Skin Neoplasms
Concept	Colorectal Neoplasms
Concept	Drug Resistance, Multiple
Concept	Brain Neoplasms
Concept	Neoplasms
Academic Article	Effect of temozolomide and dacarbazine on O6-alkylguanine-DNA alkyltransferase activity and sensitivity of human tumor cells and xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea.
Academic Article	Effect of O6-benzylguanine on the response to 1,3-bis(2-chloroethyl)-1-nitrosourea in the Dunning R3327G model of prostatic cancer.
Academic Article	Peripheral blood mononuclear cell dihydropyrimidine dehydrogenase activity in volunteers with and without diabetes mellitus.
Academic Article	Pharmacodynamics of fluorouracil-based induction chemotherapy in advanced head and neck cancer.
Academic Article	Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in vivo.
Academic Article	Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross-resistance with other anticancer agents.
Academic Article	Pharmacokinetics and pharmacodynamics of oltipraz as a chemopreventive agent.
Academic Article	Characterization of CPT-11 hydrolysis by human liver carboxylesterase isoforms hCE-1 and hCE-2.
Academic Article	Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer.
Academic Article	Inhibition of O(6)-methylguanine-DNA methyltransferase increases azoxymethane-induced colonic tumors in rats.
Academic Article	Effect of O6-benzylguanine analogues on sensitivity of human tumor cells to the cytotoxic effects of alkylating agents.
Academic Article	O6-benzylguanine in humans: metabolic, pharmacokinetic, and pharmacodynamic findings.
Academic Article	Chronic daily low dose of 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (Oltipraz) in patients with previously resected colon polyps and first degree female relatives of breast cancer patients.
Academic Article	Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer.
Academic Article	Effect of O6-benzylguanine on alkylating agent-induced toxicity and mutagenicity. In Chinese hamster ovary cells expressing wild-type and mutant O6-alkylguanine-DNA alkyltransferases.
Academic Article	O6-benzylguanine and its role in chemotherapy.
Academic Article	Phase I study of eniluracil, a dihydropyrimidine dehydrogenase inactivator, and oral 5-fluorouracil with radiation therapy in patients with recurrent or advanced head and neck cancer.
Academic Article	Role of O6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity.
Academic Article	O6-alkylguanine-DNA alkyltransferase in cutaneous T-cell lymphoma: implications for treatment with alkylating agents.
Academic Article	In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo.
Academic Article	Role of cytochrome P450 isoenzymes in metabolism of O(6)-benzylguanine: implications for dacarbazine activation.
Academic Article	Inactivation of O6-alkylguanine-DNA alkyltransferase by 8-substituted O6-benzylguanine analogs in mice.
Academic Article	Plasma and cerebrospinal fluid pharmacokinetics of O6-benzylguanine and analogues in nonhuman primates.
Academic Article	Determination of the optimal modulatory dose of O6-benzylguanine in patients with surgically resectable tumors.
Academic Article	Silence is golden: gene hypermethylation and survival in large-cell lymphoma.
Academic Article	A phase II trial of oral temozolomide in patients with metastatic renal cell cancer.
Academic Article	Effect of O6-benzylguanine on the sensitivity of human tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea and on DNA interstrand cross-link formation.
Academic Article	Effect of O6-benzylguanine on nitrogen mustard-induced toxicity, apoptosis, and mutagenicity in Chinese hamster ovary cells.
Academic Article	Temozolomide: realizing the promise and potential.
Academic Article	Role of glutathione and nucleotide excision repair in modulation of cisplatin activity with O6-benzylguanine.
Academic Article	Selective enhancement of ifosfamide-induced toxicity in Chinese hamster ovary cells.
Academic Article	Molecular mechanisms of resistance and toxicity associated with platinating agents.
Academic Article	Heritability and linkage analysis of sensitivity to cisplatin-induced cytotoxicity.
Academic Article	Effect of population and gender on chemotherapeutic agent-induced cytotoxicity.
Academic Article	Inactivation of O6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy.
Academic Article	Enhancement of platinum-induced cytotoxicity by O6-benzylguanine.
Academic Article	Identifying genetic variants that contribute to chemotherapy-induced cytotoxicity.
Academic Article	The pharmacogenetics research network: from SNP discovery to clinical drug response.
Academic Article	Genetic variants contributing to daunorubicin-induced cytotoxicity.
Academic Article	Role of copper transporters in resistance to platinating agents.
Academic Article	Population-specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity.
Academic Article	Whole-genome approach implicates CD44 in cellular resistance to carboplatin.
Academic Article	Use of cell lines in the investigation of pharmacogenetic loci.
Academic Article	Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.
Academic Article	Modulation of mammalian O6-alkylguanine-DNA alkyltransferase in vivo by O6-benzylguanine and its effect on the sensitivity of a human glioma tumor to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea.
Academic Article	The emerging role of microRNAs in drug responses.
Academic Article	Platinum sensitivity-related germline polymorphism discovered via a cell-based approach and analysis of its association with outcome in ovarian cancer patients.
Academic Article	A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor gene promoter.
Academic Article	Mixed effects modeling of proliferation rates in cell-based models: consequence for pharmacogenomics and cancer.
Academic Article	Genetic variants associated with carboplatin-induced cytotoxicity in cell lines derived from Africans.
Academic Article	PACdb: a database for cell-based pharmacogenomics.
Academic Article	Effect of O6-benzylguanine on the sensitivity of human colon tumor xenografts to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).
Academic Article	Comprehensive evaluation of the contribution of X chromosome genes to platinum sensitivity.
Academic Article	Regulatory polymorphisms in ß-tubulin IIa are associated with paclitaxel-induced peripheral neuropathy.
Academic Article	Metabolism of O6-benzylguanine, an inactivator of O6-alkylguanine-DNA alkyltransferase.
Academic Article	Biodistribution of O6-benzylguanine and its effectiveness against human brain tumor xenografts when given in polyethylene glycol or cremophor-EL.
Academic Article	Copy number polymorphisms and anticancer pharmacogenomics.
Academic Article	Human liver oxidative metabolism of O6-benzylguanine.
Academic Article	Using germline genomics to individualize pediatric cancer treatments.
Academic Article	Sequential therapy with dacarbazine and carmustine: a phase I study.
Academic Article	Susceptibility loci involved in cisplatin-induced cytotoxicity and apoptosis.
Academic Article	Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics.
Academic Article	The use of genomic information to optimize cancer chemotherapy.
Academic Article	Identification of novel germline polymorphisms governing capecitabine sensitivity.
Academic Article	Lack of evidence for a polymorphism at codon 160 of human O6-alkylguanine-DNA alkyltransferase gene in normal tissue and cancer.
Academic Article	Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer.
Academic Article	Pharmacokinetics of oral O6-benzylguanine and evidence of interaction with oral ketoconazole in the rat.
Academic Article	Irinotecan activation by human carboxylesterases in colorectal adenocarcinoma cells.
Academic Article	Role of MGMT in protecting against cyclophosphamide-induced toxicity in cells and animals.
Academic Article	Mapping genes that contribute to daunorubicin-induced cytotoxicity.
Academic Article	Inhibition of nuclear factor-kappaB activity by temozolomide involves O6-methylguanine induced inhibition of p65 DNA binding.
Academic Article	Approaches to the discovery of pharmacogenomic markers in oncology: 2000-2010-2020.
Academic Article	Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers.
Academic Article	Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans.
Academic Article	Effect of 1,19-bis(ethylamino)-5,10,15-triazanonadecane on human tumor xenografts.
Academic Article	Enhancement of nitrosourea activity in medulloblastoma and glioblastoma multiforme.
Academic Article	Effect of O6-alkylguanine pretreatment on the sensitivity of human colon tumor cells to the cytotoxic effects of chloroethylating agents.
Academic Article	Investigation of the specificity of O6-alkylguanine-DNA-alkyltransferase.
Academic Article	Effect of O6-methylguanine on DNA interstrand cross-link formation by chloroethylnitrosoureas and 2-chloroethyl(methylsulfonyl)methanesulfonate.
Academic Article	Comparison of the rates of repair of O6-alkylguanines in DNA by rat liver and bacterial O6-alkylguanine-DNA alkyltransferase.
Academic Article	Correlation between O6-methylguanine-DNA-methyltransferase activity and resistance of human cells to the cytotoxic and mutagenic effect of N-methyl-N'-nitro-N-nitrosoguanidine.
Academic Article	Increased killing of prostate, breast, colon, and lung tumor cells by the combination of inactivators of O6-alkylguanine-DNA alkyltransferase and N,N'-bis(2-chloroethyl)-N-nitrosourea.
Academic Article	Activity of temozolomide in the treatment of central nervous system tumor xenografts.
Academic Article	Reduction of O6-alkylguanine-DNA alkyltransferase activity in HeLa cells treated with O6-alkylguanines.
Academic Article	The effects of O6-benzylguanine and hypoxia on the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea in nitrosourea-resistant SF-763 cells.
Academic Article	Intracellular Localization and intercellular heterogeneity of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase.
Academic Article	Elevated DNA polymerase alpha, DNA polymerase beta, and DNA topoisomerase II in a melphalan-resistant rhabdomyosarcoma xenograft that is cross-resistant to nitrosoureas and topotecan.
Academic Article	Treatment of subcutaneous and intracranial brain tumor xenografts with O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea.
Academic Article	Substituted O6-benzylguanine derivatives and their inactivation of human O6-alkylguanine-DNA alkyltransferase.
Academic Article	Distribution and functional consequences of nucleotide polymorphisms in the 3'-untranslated region of the human Sep15 gene.
Academic Article	O6-benzylguanine potentiates the antitumor effect of locally delivered carmustine against an intracranial rat glioma.
Academic Article	Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.
Academic Article	O6-benzylguanine-mediated enhancement of nitrosourea activity in Mer- central nervous system tumor xenografts--implications for clinical trials.
Academic Article	Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.
Academic Article	Phase I pharmacokinetic and pharmacodynamic study of temozolomide in pediatric patients with refractory or recurrent leukemia: a Children's Oncology Group Study.
Academic Article	Somatic acquisition and signaling of TGFBR1*6A in cancer.
Academic Article	Intraarterial O6-benzylguanine enables the specific therapy of nitrosourea-resistant intracranial human glioma xenografts in athymic rats with 1,3-bis(2-chloroethyl)-1-nitrosourea.
Academic Article	Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.
Academic Article	Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkyltransferase.
Academic Article	Allelic loss at the GPx-1 locus in cancer of the head and neck.
Academic Article	A phase II trial of O6-benzylguanine and carmustine in patients with advanced soft tissue sarcoma.
Academic Article	Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma.
Academic Article	Poly(ADP-ribose) polymerase inhibitor ABT-888 potentiates the cytotoxic activity of temozolomide in leukemia cells: influence of mismatch repair status and O6-methylguanine-DNA methyltransferase activity.
Academic Article	Schedule-dependent activity of temozolomide plus CPT-11 against a human central nervous system tumor-derived xenograft.
Academic Article	Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.
Academic Article	O6-benzylguanine-mediated enhancement of chemotherapy.
Academic Article	Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous O6-benzylguanine in adults with recurrent malignant glioma: new approaches to brain tumor therapy CNS consortium trial.
Academic Article	Brain tumor cell lines resistant to O6-benzylguanine/1,3-bis(2-chloroethyl)-1-nitrosourea chemotherapy have O6-alkylguanine-DNA alkyltransferase mutations.
Academic Article	Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations.
Academic Article	Cancer pharmacogenomics: strategies and challenges.
Academic Article	Comprehensive genetic analysis of cytarabine sensitivity in a cell-based model identifies polymorphisms associated with outcome in AML patients.
Academic Article	Testicular cancer survivorship: research strategies and recommendations.
Academic Article	Multicenter phase II trial of temozolomide in mycosis fungoides/sezary syndrome: correlation with O6-methylguanine-DNA methyltransferase and mismatch repair proteins.
Academic Article	MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11.
Academic Article	Depletion of O6-alkylguanine-DNA alkyltransferase activity in mammalian tissues and human tumor xenografts in nude mice by treatment with O6-methylguanine.
Academic Article	Use of oligodeoxynucleotides containing O6-alkylguanine for the assay of O6-alkylguanine-DNA-alkyltransferase activity.
Academic Article	Extended depletion of O6-methylguanine-DNA methyltransferase activity following O6-benzyl-2'-deoxyguanosine or O6-benzylguanine combined with streptozotocin treatment enhances 1,3-bis(2-chloroethyl)-1-nitrosourea cytotoxicity.
Academic Article	Prolonged depletion of O6-methylguanine DNA methyltransferase activity following exposure to O6-benzylguanine with or without streptozotocin enhances 1,3-bis(2-chloroethyl)-1-nitrosourea sensitivity in vitro.
Academic Article	Mechanisms of resistance to the toxicity of cyclophosphamide.
Academic Article	Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft.
Academic Article	Trans-population analysis of genetic mechanisms of ethnic disparities in neuroblastoma survival.
Academic Article	Pharmacokinetics and pharmacogenomics of daunorubicin in children: a report from the Children's Oncology Group.
Academic Article	EPS8 inhibition increases cisplatin sensitivity in lung cancer cells.
Academic Article	The role of gene body cytosine modifications in MGMT expression and sensitivity to temozolomide.
Academic Article	Chemotherapy-induced peripheral neurotoxicity and ototoxicity: new paradigms for translational genomics.
Academic Article	Identification of genetic variants associated with capecitabine-induced hand-foot syndrome through integration of patient and cell line genomic analyses.
Academic Article	Integrating cell-based and clinical genome-wide studies to identify genetic variants contributing to treatment failure in neuroblastoma patients.
Academic Article	Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy.
Academic Article	Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer.
Academic Article	Cell-based Models for Discovery of Pharmacogenomic Markers of Anticancer Agent Toxicity.
Academic Article	Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy.
Academic Article	Variants in WFS1 and Other Mendelian Deafness Genes Are Associated with Cisplatin-Associated Ototoxicity.
Academic Article	Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach.
Academic Article	Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer.
Academic Article	Genome-Wide Association Studies of Chemotherapeutic Toxicities: Genomics of Inequality.
Award or Honor Receipt	Ambassador of Hope
Award or Honor Receipt	Presidential Award for Volunteer Contributions to Research
Academic Article	Integration of genetic and functional genomics data to uncover chemotherapeutic induced cytotoxicity.
Academic Article	Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities.
Academic Article	Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.
Academic Article	Racial disparities in omission of oncotype DX but no racial disparities in chemotherapy receipt following completed oncotype DX test results.
Academic Article	Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms.
Academic Article	Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy.
Academic Article	Genomic Variants of Cytarabine Sensitivity Associated with Treatment-Related Mortality in Pediatric AML: A Report from the Children's Oncology Group.
Academic Article	Clinical evaluation of germline polymorphisms associated with capecitabine toxicity in breast cancer: TBCRC-015.
Academic Article	Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors.
Academic Article	Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors.
Academic Article	Genetically regulated expression underlies cellular sensitivity to chemotherapy in diverse populations.
Academic Article	Identification of small molecules that mitigate vincristine-induced neurotoxicity while sensitizing leukemia cells to vincristine.
Academic Article	Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.
Academic Article	Pharmacogenomics of cisplatin-induced neurotoxicities: Hearing loss, tinnitus, and peripheral sensory neuropathy.
Academic Article	Comprehensive association analysis of speech recognition thresholds after cisplatin-based chemotherapy in survivors of adult-onset cancer.
Academic Article	Comparison of vaginal microbiota in gynecologic cancer patients pre- and post-radiation therapy and healthy women.
Academic Article	Prevalence and risk factors for ototoxicity after cisplatin-based chemotherapy.
Concept	Cancer Survivors
Concept	Prostatic Neoplasms, Castration-Resistant

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Cancer
drug resistance