Allyson E. Koyen
Emory University
Homologous recombinationNucleotide excision repairMessenger RNACancerDNA repairCell migrationDDB1Function (biology)PathologyMutantDNA damageVimentinTranslation (biology)Molecular biologyResectionPyrimidine dimerReceptorSTAT proteinGenome instabilityPoly ADP ribose polymeraseKinaseSIRT2ImmunologyImmunohistochemistryIn vivoTumor microenvironmentLung cancerSAMHD1ChemotherapyHistone H3PRC2ImmunotherapyLungOsteosarcomaCisplatinTumor suppressor genestatSynthetic lethalitySTAT3MetastasisEpidermal growth factor receptorPancreatic cancerPrimary tumorSirtuinAdenocarcinomaDeacetylase activityGenome integrityControl cellCancer treatmentTranscription (biology)EZH2Cancer researchRadiation therapyGeneticsDNACarcinogenesisMotilityMedicineEpithelial–mesenchymal transitionPI3K/AKT/mTOR pathwayBiologyImmune systemMethyltransferaseCell biologyCancer cellProtein kinase A
Publications 10
#1Allyson E. Koyen (Emory University)H-Index: 5
#2Matthew Z. Madden (Emory University)H-Index: 7
Last. David S. Yu (Emory University)H-Index: 22
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Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor outcomes associated with resistance to cisplatin-based chemotherapy. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2), which silences transcription through trimethylation of histone H3 lysine 27 (H3K27me3) and has emerged as an important therapeutic target with inhibitors targeting its methyltransferase activity under clinical investigation. Here, we show that EZH2 has a n...
8 CitationsSource
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, with a five-year survival rate of 7%. Cisplatin-based chemotherapy is the first line treatment for SCLC; however, many patients develop treatment resistance and experience tumor recurrence. Targeting proteins critical to the repair of cisplatin DNA crosslinks is a strategy for overcoming acquired cisplatin resistance in SCLC, but many proteins that mediate crosslink repair have yet to be identified. To address this issue, ...
#1David S. YuH-Index: 22
Last. B. Kim
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#1Alessandra M. Richardson (Emory University)H-Index: 1
#2Lauren S. Havel (Emory University)H-Index: 6
Last. Adam I. Marcus (Emory University)H-Index: 34
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Purpose: Vimentin is an epithelial-to-mesenchymal transition (EMT) biomarker and intermediate filament protein that functions during cell migration to maintain structure and motility. Despite the abundance of clinical data linking vimentin to poor patient outcome, it is unclear if vimentin is required for metastasis or is a correlative biomarker. We developed a novel genetically engineered mouse model (GEMM) to probe vimentin in lung adenocarcinoma metastasis. Experimental Design: We used the LS...
81 CitationsSource
#1Allyson E. Koyen (Emory University)H-Index: 5
#2Geraldine N. Nabeta (Emory University)H-Index: 1
Last. Waaqo Daddacha (Emory University)H-Index: 12
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Protein kinases play a vital role in the regulation of pathways that control cell growth, proliferation, survival, and differentiation. Epidermal growth factor receptor (EGFR) is a key protein kinase that when dysregulated, disrupts these pathways and, accordingly, is associated with several cancers. Thus, EGFR has been a focus of investigation as a therapeutic target for cancer treatment for the past several decades, with fair success. Despite this success, EGFR-targeted therapies are not unive...
#1Waaqo Daddacha (Emory University)H-Index: 12
#2Allyson E. Koyen (Emory University)H-Index: 5
Last. David S. Yu (Emory University)H-Index: 22
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Summary DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutieres syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-i...
82 CitationsSource
#1PamelaSara E. HeadH-Index: 6
#2Hui ZhangH-Index: 46
Last. David S. YuH-Index: 22
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Abstract Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although Sirt2 deficiency in mice leads to tumorigenesis, the functional significance of somatic SIRT2 mutations in human tumors is unclear. Using structural insight combined with bioinformatics and functional analyses, we show that naturally occurring cancer-associated SIRT2 mutations at evolutionarily conserved sites disrupt its deacetylation of DNA-damage response proteins ...
14 CitationsSource
#1Waaqo Daddacha (Emory University)H-Index: 12
#2Allyson E. Koyen (Emory University)H-Index: 5
Last. David S. Yu (Emory University)H-Index: 22
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STAT3 is a member of the signal transducer and activator of transcription (STAT) family of proteins. Activation of the STAT3 signaling cascade results in the transcription of several pro-proliferative and anti-apoptotic proteins. STAT3 is also a potent modulator of the immune system, and its activation results in the suppression of the immune response. Dysregulation of STAT3 is implicated in the development and progression of a number of malignancies, including pancreatic ductal adenocarcinoma. ...
#1James J. Morrow (Case Western Reserve University)H-Index: 11
#2Arnulfo MendozaH-Index: 26
Last. Chand Khanna (NIH: National Institutes of Health)H-Index: 64
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Purpose: To successfully metastasize, tumor cells must respond appropriately to biological stressors encountered during metastatic progression. We sought to test the hypothesis that enhanced efficiency of mRNA translation during periods of metastatic stress is required for metastatic competence of osteosarcoma and that this metastasis-specific adaptation is amenable to therapeutic intervention. Experimental Design: We employ novel reporter and proteomic systems that enable tracking of mRNA trans...
9 CitationsSource
#1Alessandra M. Salgueiro (Emory University)H-Index: 1
#2Melissa Gilbert-Ross (Emory University)H-Index: 4
Last. Adam I. Marcus (Emory University)H-Index: 34
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Vimentin is an intermediate filament protein that has been used in the clinic as a biomarker for metastatic potential and poor patient prognosis across numerous solid tumor types; however, little is known about how vimentin might contribute to cancer progression and metastasis. Here we created a novel genetically engineered mouse model (GEMM) to study the role of vimentin in lung cancer progression and metastasis. We first re-developed an LSL-KrasG12D,LKB1fl/fl mouse model whereby intranasal adm...