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INFORMATION FOR

Peter M. Glazer, MD, PhD

Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Therapeutic Radiology

Research Summary

Tumor hypoxia, DNA repair, and cancer therapy: Our work established that hypoxia is a key driver of genetic instability in solid tumors. We have shown that tumor hypoxia causes down-regulation of specific DNA repair genes, particularly the homology-dependent repair factors, BRCA1 and RAD51. This down-regulation of DNA repair in hypoxic cancer cells renders them vulnerable to therapeutic strategies that exploit the specific repair deficiencies, providing the basis for novel, rationally designed cancer therapies. We also discovered that the anti-angiogenic agent, cediranib, not only damages tumors by interrupting their blood supply and thereby inducing hypoxia but also down-regulates DNA repair (Kaplan, Science Translational Medicine), sensitizing cancer cells to PARP inhibitors and highlighting a therapeutic strategy that is currently being pursued in clinical trials.

Oncometabolites and DNA repair. In collaborative work with the Bindra lab published in Science Translational Medicine, Nature Genetics, and Nature, we found that elevated levels of the metabolites, 2-hydroxyglutarate, fumarate, and succinate, generated in human malignancies by neomorphic IDH mutations or by inherited mutations in the fumarate hydratase or succinate dehydrogenase genes, also suppress DNA repair via dysregulation of chromatin signaling and induce PARP inhibitor sensitivity, providing a new approach to treat these cancers that is being tested in current clinical trials.

DNA repair inhibitors for cancer therapy. We have made the unexpected finding that a cell-penetrating lupus autoantibody, 3E10, has potential as a targeted therapy for DNA-repair deficient malignancies (Hansen, Science Translational Medicine 2012). We found that 3E10 is synthetically lethal to BRCA2- or PTEN-deficient human cancer cells and sensitizes such cells to radiation and doxorubicin. Mechanistically we found that the 3E10 antibody binds to and inhibits the DNA repair factor, RAD51 (Turchick, NAR, 2019), providing a basis for its effects.

Tumor specific targeting of microRNAs and other undruggable targets. We have examined microRNA regulation of DNA repair, identifying several key microRNAs that mediate the stress response to hypoxia and to radiation. This work led to a collaborative effort to target peptide nucleic acids (PNAs) to tumors in mice using pH sensitive peptides as a means to inhibit oncogenic microRNA pathways (Cheng, Nature, 2015). We recently applied this approach to deliver antisense PNAs to inhibit the otherwise undruggable DNA repair factor, Ku80, to sensitize tumors to radiation (Kaplan, Molecular Cancer Research, 2020).

Gene editing via triple helix formation: From an interest in studying cellular DNA repair and recombination pathways, we recognized the utility of DNA triple helix formation as a mechanism for the site-specific induction of gene editing in human cells. We are focusing on triplex forming peptide nucleic acids (PNAs), delivered via polymer nanoparticles, as tools to mediate targeted modification of human disease-related genes. In collaborative work with the Saltzman, Egan, Gallagher, and Kumar labs, we have been optimizing this approach for application in human hematopoietic stem cells and in mouse models of human genetic diseases (Bahal, Nature Communications 2016, Ricciardi, Nature Communications 2018).

Extensive Research Description

Novel pathways that regulate the DNA damage response. Recently, in collaborative work with the Bindra lab, we discovered that the oncometabolite, 2-hydroxyglutarate, generated by neomorphic IDH mutations in gliomas and other maligancies suppresses homologous recombination and confers PARP inhibitor sensitivity, identifying a new approach to treat these malignancies (Sulkowski, Science Translational Medicine, 2017). Similarly, we found that elevated level of the Krebs cycle intermediates, fumarate and succinate, associated with the hereditary cancer syndromes, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) and Succinate Dehydrogenase-related Hereditary Paraganglioma and Pheochromocytoma (SDH PGL/PCC), also suppress the homologous recombination pathway, rendering these tumors vulnerable to synthetic lethal targeting with PARP inhibitors, pointing to a new therapeutic approach for advanced HLRCC and SDH PGL/PCC, both incurable when metastatic (Sulkowski, Nature Genetics, 2018). The use of PARP inhibitors in these malignancies is currently being tested in several clinical trials directly based on our work. Mechanistically, we determined that oncometabolites suppress homology dependent repair (HDR) by inhibiting the histone lysine demethylase, KDM4B. This causes aberrant hypermethylation of H3K9 across the genome and thereby disrupts the normal temporal and spatial pattern of HDR factor recruitment to sites of DNA DSBs (Sulkowski, Nature, 2020). We also recently characterized a novel pathway by which mitochondrial DNA damage mediates signaling to upregulate nuclear DNA repair (Wu, Nature Metabolism, 2019).

Novel approaches to cancer therapy. Effective cancer treatment depends on achieving a therapeutic window in which there is greater toxicity to the malignant cells than to normal, healthy tissue. We have sought to exploit synthetic lethality by seeking agents that are more toxic to cancer cells deficient in homology-dependent DNA repair. This applies to cancers with genetic defects in genes such as BRCA1, BRCA2, PALB2, and PTEN. But it also applies to hypoxic cancer cells in which there is down-regulation of the HDR genes, BRCA1 and RAD51. Our efforts in this area have focused on a novel lupus-derived, cell-penetrating antibody that functions as a DNA repair inhibitor to radiosensitize cells (Hansen, Science Translational Medicine 2012) and a promising class of natural products (Colis, Nature Chemistry 2014). We have also sought to exploit the acidic tumor microenvironment using a novel pH-dependent trans-membrane delivery peptide (pHLIP) to introduce anti-microRNA peptide nucleic acids (PNAs) antisense agents to disrupt oncomiR addiction (Cheng, Nature 2015). We recently applied this approach to deliver antisense PNAs to inhibit the otherwise undruggable DNA repair factor, Ku80, to sensitize tumors to radiation (Kaplan, Molecular Cancer Research, 2020). Recently, we have shown that the anti-angiogenic agent, cediranib, not only damages tumors by interrupting their blood supply and thereby inducing hypoxia but also directly down-regulates DNA repair, sensitizing cancer cells to PARP inhibitors and suggesting a strategy for targeted treatment that is currently being pursued in several clinical trials at Yale and elsewhere (Kaplan, Science Translational Medicine, 2019).

Hypoxia causes genetic instability, down-regulates DNA repair, and promotes gene silencing. In the mid 1990's, we developed the hypothesis that the hypoxic tumor microenvironment could be a cause of genetic instability in cancer. This was contrary to the dogma at the time, because it was thought that under hypoxia there would be less oxidative damage to DNA. We showed that growth of cancer cells in vivo in tumor xenografts produces an elevated mutation rate compared to growth of the same cells in culture (Reynolds, Cancer Res. 1996), and we went on to demonstrate that this effect could be attributed to hypoxia. Since then, we have systematically dissected the mechanisms underlying this effect. These mechanisms include transcriptional downregulation of the homology-dependent repair genes RAD51 and BRCA1 (Bindra, Cancer Res. 2006), of the Fanconi pathway gene FANCD2(Scanlon, Molecular Cancer Res. 2014) and of the mismatch repair gene, MLH1 (Mihaylova, Mol. Cell. Biol. 2003) plus induction of microRNAs 210 and 373 that suppress expression of several DNA repair factors (Crosby, Cancer Res. 2009). In addition, besides acute transcriptional downregulation, our laboratory discovered that hypoxia promotes silencing of the DNA repair genes, BRCA1 and MLH1, in a pathway that is dependent on the histone lysine demethylase, LSD-1 (Lu, Mol. Cell. Biol. 2011 and Lu, Cell Reports 2014).

Triplex DNA provokes DNA repair, and triplex-forming oligonucleotides can stimulate site-specific gene editing in vivo. In the early 1990's, triplex-forming oligonucleotides (TFOs) were being touted as tools to suppress gene expression by binding to promoter sites to block transcription factor access. However, I realized that the site-specific binding properties of TFOs could also be used to mediate sequence-specific gene editing. We discovered that triplex formation, itself, constitutes a helical alteration sufficient to induce DNA repair at the site of the triplex (Wang, Science 1996 and Vasquez, Science 2000), via the nucleotide excision repair (NER) pathway. This activates the target site for recombination with "donor DNAs" via homology-dependent repair. After a systematic evaluation of DNA analogs for improved triple helix formation in cells, we have focused on peptide nucleic acids (PNAs), which have a neutral polyamide backbone and bind DNA with high affinity. Using PNAs, we demonstrated successful editing of the beta-globin gene in human primary hematopoietic stem cells. In collaboration with the Saltzman lab, we developed a strategy to encapsulate the PNAs and donor DNAs in polymer-based, biocompatible nanoparticles to achieve effective in vivo delivery in mice with minimal toxicity. Recent work with the Egan lab has demonstrated the ability of nanoparticles containing PNAs and donor DNAs to mediate editing of the F508del CFTR gene mutation in airway epithelia in vivo in a mouse model of cystic fibrosis (McNeer, Nature Communications 2015) and to mediate substantial correction of anemia and in mice with thalassemia by simple intravenous injection of PNA and DNA containing nanoparticles in adult mice (Bahal, Nature Communications 2016) and in fetal mice via in utero injection (Ricciardi, Nature Communications, 2018).

Coauthors

Research Interests

DNA Repair; Genetics; Radiation; Gene Targeting; Radiation Oncology; Recombinational DNA Repair; Gene Editing

Research Image

Selected Publications

  • Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acidsPutman R, Ricciardi A, Carufe K, Quijano E, Bahal R, Glazer P, Saltzman W. Nanoparticle‐mediated genome editing in single‐cell embryos via peptide nucleic acids Bioengineering & Translational Medicine 2022 DOI: 10.1002/btm2.10458.
  • Abstract 663: Systemic targeting of therapeutic RNA to cancer via a novel, cell-penetrating and nucleic acid binding, monoclonal antibodyQuijano E, Saucedo D, Khang M, Liu Y, Ludwig D, Turner B, Squinto S, Bindra R, Saltzman W, Escobar-Hoyos L, Glazer P. Abstract 663: Systemic targeting of therapeutic RNA to cancer via a novel, cell-penetrating and nucleic acid binding, monoclonal antibody Cancer Research 2022, 82: 663-663. DOI: 10.1158/1538-7445.am2022-663.
  • Chapter 11 Oncometabolites, epigenetic marks, and DNA repairDow J, Glazer P. Chapter 11 Oncometabolites, epigenetic marks, and DNA repair 2022, 191-202. DOI: 10.1016/b978-0-323-91081-1.00008-x.
  • Abstract P135: Systemic targeting of a CNS tumor (medulloblastoma) using a novel cell-penetrating, nucleic acid binding, monoclonal antibodyQuijano E, Khang M, Turner B, Squinto S, Bindra R, Saltzman W, Glazer P. Abstract P135: Systemic targeting of a CNS tumor (medulloblastoma) using a novel cell-penetrating, nucleic acid binding, monoclonal antibody Molecular Cancer Therapeutics 2021, 20: p135-p135. DOI: 10.1158/1535-7163.targ-21-p135.
  • 582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatmentPiotrowski-Daspit A, Bracaglia L, Barone C, Nguyen R, Glazer P, Egan M, Saltzman W. 582: In vivo nanoparticle-mediated therapeutic nucleic acid delivery for CF treatment Journal Of Cystic Fibrosis 2021, 20: s277. DOI: 10.1016/s1569-1993(21)02005-1.
  • Abstract LB169: Systemic Administration of an antibody/RNA complex results in tumor specific delivery of immunostimulatory RNAs and tumor growth suppression in a mouse model of melanomaQuijano E, Liu Y, Squinto S, Turner B, Glazer P. Abstract LB169: Systemic Administration of an antibody/RNA complex results in tumor specific delivery of immunostimulatory RNAs and tumor growth suppression in a mouse model of melanoma Cancer Research 2021, 81: lb169-lb169. DOI: 10.1158/1538-7445.am2021-lb169.
  • Abstract 6242: Development of alphalex™-toxin low pH targeting conjugates for the treatment of solid tumorsGayle S, Aiello R, Bechtold J, Bourassa P, Csengery J, Deshpande K, Jones K, Lopresti-Morrow L, Maguire R, Marshall D, Moore H, Paradis T, Tylaska L, Zhang Q, Volkmann R, Bindra R, Glazer P, Paralkar V. Abstract 6242: Development of alphalex™-toxin low pH targeting conjugates for the treatment of solid tumors Cancer Research 2020, 80: 6242-6242. DOI: 10.1158/1538-7445.am2020-6242.
  • Abstract 6249: CBX-12: A low pH targeting alphalex™-exatecan conjugate for the treatment of solid tumorsAiello R, Gayle S, Bechtold J, Bourassa P, Csengery J, Deshpande K, Jones K, Lopresti-Morrow L, Maguire R, Marshall D, Moore H, Paradis T, Tylaska L, Zhang Q, Volkmann R, Bindra R, Glazer P, Paralkar V. Abstract 6249: CBX-12: A low pH targeting alphalex™-exatecan conjugate for the treatment of solid tumors Cancer Research 2020, 80: 6249-6249. DOI: 10.1158/1538-7445.am2020-6249.
  • Abstract 1877: Hypoxia induces EGFR inhibitor resistance in lung cancer cells by upregulation of fibroblast growth factor receptor 1 (FGFR1) via MAPK pathwayLu Y, Liu Y, Oeck S, Zhang G, Glazer P. Abstract 1877: Hypoxia induces EGFR inhibitor resistance in lung cancer cells by upregulation of fibroblast growth factor receptor 1 (FGFR1) via MAPK pathway Cancer Research 2020, 80: 1877-1877. DOI: 10.1158/1538-7445.am2020-1877.
  • Abstract SY21-02: Oncometabolites suppress homologous recombination DNA repair by inhibition of chromatin remodeling at the DNA double-strand breakSulkowski P, Oeck S, Li J, Shuch B, King M, Bindra R, Glazer P. Abstract SY21-02: Oncometabolites suppress homologous recombination DNA repair by inhibition of chromatin remodeling at the DNA double-strand break 2019, sy21-02-sy21-02. DOI: 10.1158/1538-7445.sabcs18-sy21-02.
  • Abstract SY21-02: Oncometabolites suppress homologous recombination DNA repair by inhibition of chromatin remodeling at the DNA double-strand breakSulkowski P, Oeck S, Li J, Shuch B, King M, Bindra R, Glazer P. Abstract SY21-02: Oncometabolites suppress homologous recombination DNA repair by inhibition of chromatin remodeling at the DNA double-strand break Cancer Research 2019, 79: sy21-02-sy21-02. DOI: 10.1158/1538-7445.am2019-sy21-02.
  • Abstract 2981: Targeting solid tumor acidic microenvironment with an alphalex PARP inhibitorParalkar V, Aiello R, Marshall D, Csengery J, Bourassa P, Zhang Q, Robinson B, Lopresti-Morrow L, Bechtold J, Tylaska L, Paradis T, Slaybaugh G, Visca H, Moshnikova A, Weerakkody D, Andreev O, Reshetnyak Y, Engelman D, Bindra R, Glazer P, Hellsund P. Abstract 2981: Targeting solid tumor acidic microenvironment with an alphalex PARP inhibitor Cancer Research 2019, 79: 2981-2981. DOI: 10.1158/1538-7445.am2019-2981.
  • Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform.Bindra R, Sundaram R, Aiello R, Marshall D, Bourassa P, Csengery J, Zhang Q, Robinson B, lopresti-Morrow L, Bechtold J, Tylaska L, Paradis T, Paralkar V, Hellsund P, Glazer P. Unlocking PARP inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform inhibitor efficacy for HRD-negative cancers using the alphalex tumor targeting platform. Journal Of Clinical Oncology 2019, 37: e14664-e14664. DOI: 10.1200/jco.2019.37.15_suppl.e14664.
  • Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and RadiationCorso C, Bindra R, Glazer P, Sulkowski P, Robinson N, Scanlon S, Purshouse K, Bai H, Liu Y, Sundaram R, Hegan D, Fons N, Breuer G, Song Y, Mishra-Gorur K, De Feyter H, de Graaf R, Surovtseva Y, Kachman M, Halene S, Gunel M. Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and Radiation International Journal Of Radiation Oncology • Biology • Physics 2017, 99: e68. DOI: 10.1016/j.ijrobp.2017.06.754.
  • Abstract LB-290: Oncometabolites induce a BRCAness state that can be exploited by PARP inhibitorsSulkowski P, Corso C, Robinson N, Scanlon S, Purshouse K, Bai H, Liu Y, Sundaram R, Hegan D, Fons N, Breuer G, Song Y, Mishra K, Feyter H, Graaf R, Surovtseva Y, Kachman M, Halene S, Gunel M, Glazer P, Bindra R. Abstract LB-290: Oncometabolites induce a BRCAness state that can be exploited by PARP inhibitors Cancer Research 2017, 77: lb-290-lb-290. DOI: 10.1158/1538-7445.am2017-lb-290.
  • Abstract 2480: Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinomaScanlon S, Sulkowski P, Glazer P. Abstract 2480: Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma Cancer Research 2017, 77: 2480-2480. DOI: 10.1158/1538-7445.am2017-2480.
  • Abstract 2482: Inhibition of RAD51 with a cell penetrating antibody, 3E10Glazer P, Turchick A. Abstract 2482: Inhibition of RAD51 with a cell penetrating antibody, 3E10 Cancer Research 2017, 77: 2482-2482. DOI: 10.1158/1538-7445.am2017-2482.
  • Induction of a BRCAness state by oncometabolites and exploitation by PARP inhibitors.Bindra R, Sulkowski P, Corso C, Glazer P, Shuch B. Induction of a BRCAness state by oncometabolites and exploitation by PARP inhibitors. Journal Of Clinical Oncology 2017, 35: 11586-11586. DOI: 10.1200/jco.2017.35.15_suppl.11586.
  • Abstract B25: “TargetDBR”—A DNA repair drug and target discovery collaboration: Exploiting synthetic lethal, high content, and functional cellular reporter assays to accelerate DNA repair targeted drug discoveryHollick J, Abriola L, Bono F, Hegan D, Klingbeil P, Liu Y, Sundaram R, Surovtseva Y, Whittaker M, Bindra R, Glazer P. Abstract B25: “TargetDBR”—A DNA repair drug and target discovery collaboration: Exploiting synthetic lethal, high content, and functional cellular reporter assays to accelerate DNA repair targeted drug discovery Molecular Cancer Research 2017, 15: b25-b25. DOI: 10.1158/1557-3125.dnarepair16-b25.
  • Regulation of DNA Repair by HypoxiaLu Y, Glazer P. Regulation of DNA Repair by Hypoxia 2016, 169-188. DOI: 10.1142/9789813147324_0007.
  • Chemically Modified Gamma PNAs Targeting microRNA-210 as a Novel Anticancer Therapy With Specificity for Hypoxic Solid TumorsGlazer P, Gupta A, Liu Y, Quijano E, Saltzman W. Chemically Modified Gamma PNAs Targeting microRNA-210 as a Novel Anticancer Therapy With Specificity for Hypoxic Solid Tumors International Journal Of Radiation Oncology • Biology • Physics 2016, 96: e597. DOI: 10.1016/j.ijrobp.2016.06.2125.
  • Abstract 1075: Chemically modified gamma PNAs targeting oncomiR-210 as a potential anticancer therapyGupta A, Liu Y, Quijano E, Saltzman W, Glazer P. Abstract 1075: Chemically modified gamma PNAs targeting oncomiR-210 as a potential anticancer therapy Cancer Research 2016, 76: 1075-1075. DOI: 10.1158/1538-7445.am2016-1075.
  • Abstract 2748: Targeting DNA repair deficient cancers with the cell-penetrating autoantibody 3E10Turchick A, Glazer P. Abstract 2748: Targeting DNA repair deficient cancers with the cell-penetrating autoantibody 3E10 Cancer Research 2016, 76: 2748-2748. DOI: 10.1158/1538-7445.am2016-2748.
  • Abstract LB-029: Negative transcriptional and epigenetic regulation of DNA repair pathways by the heavy metals nickel and arsenicScanlon S, Scanlon C, Hegan D, Sulkowski P, Glazer P. Abstract LB-029: Negative transcriptional and epigenetic regulation of DNA repair pathways by the heavy metals nickel and arsenic Cancer Research 2016, 76: lb-029-lb-029. DOI: 10.1158/1538-7445.am2016-lb-029.
  • Precise Genome Modification Using Triplex Forming Oligonucleotides and Peptide Nucleic AcidsBahal R, Gupta A, Glazer P. Precise Genome Modification Using Triplex Forming Oligonucleotides and Peptide Nucleic Acids 2016, 93-110. DOI: 10.1007/978-1-4939-3509-3_6.
  • E2F8 and its target genes as novel therapeutic targets for lung cancerPark S, Lee J, Platt J, Sweasy J, Glazer P, Herbst R, Koo J. E2F8 and its target genes as novel therapeutic targets for lung cancer Journal Of Thoracic Oncology 2016, 11: s29. DOI: 10.1016/j.jtho.2015.12.048.
  • Genomic predictors of biochemical failure following radical prostatectomy.Aneja S, Yu J, Glazer P. Genomic predictors of biochemical failure following radical prostatectomy. Journal Of Clinical Oncology 2016, 34: 114-114. DOI: 10.1200/jco.2016.34.2_suppl.114.
  • mRNA Expression of TP53 Attenuates Survival of HPV+ Locally Advanced Head and Neck CancerAneja S, Contessa J, Husain Z, Glazer P, Hansen J, Bindra R, Yu J. mRNA Expression of TP53 Attenuates Survival of HPV+ Locally Advanced Head and Neck Cancer International Journal Of Radiation Oncology • Biology • Physics 2015, 93: e350-e351. DOI: 10.1016/j.ijrobp.2015.07.1440.
  • Genomic Predictors of Biochemical Failure Following Radical ProstatectomyAneja S, Gross C, Glazer P, Yu J. Genomic Predictors of Biochemical Failure Following Radical Prostatectomy International Journal Of Radiation Oncology • Biology • Physics 2015, 93: e251-e252. DOI: 10.1016/j.ijrobp.2015.07.1180.
  • Abstract 2887: Epigenetic silencing of the DNA repair genes, BRCA1 and MLH1, induced by hypoxic stress in a pathway dependent on the histone demethylase, LSD1Lu Y, Chu A, Wajapeyee N, Turker M, Glazer P. Abstract 2887: Epigenetic silencing of the DNA repair genes, BRCA1 and MLH1, induced by hypoxic stress in a pathway dependent on the histone demethylase, LSD1 2015, 2887-2887. DOI: 10.1158/1538-7445.am2015-2887.
  • pHLIP® Targeting and Delivery of PNA to Silence MicroRNA in Tumor Cells§Engelman D, Cheng C, Bahal R, Babar I, Pincus Z, Barrera F, Liu C, Svoronos A, Braddock D, Glazer P, Saltzman W, Slack F. pHLIP® Targeting and Delivery of PNA to Silence MicroRNA in Tumor Cells§ Biophysical Journal 2015, 108: 552a. DOI: 10.1016/j.bpj.2014.11.3029.
  • Abstract 977: Characterizing the regulation and function of miR-155 in hypoxia biologyCzochor J, Glazer P. Abstract 977: Characterizing the regulation and function of miR-155 in hypoxia biology 2014, 977-977. DOI: 10.1158/1538-7445.am2014-977.
  • Imaging and Treating Tumors by Targeting their Acidity with Phlip, a Ph-Sensitve Insertion PeptideEngelman D, An M, Andreev O, Barrera F, Bahal R, Bosenberg M, Cheng C, Glazer P, Karabadzhak A, Reshetnyak Y, Saltzman W, Slack F, Svoronos A, Thevenin D. Imaging and Treating Tumors by Targeting their Acidity with Phlip, a Ph-Sensitve Insertion Peptide Biophysical Journal 2014, 106: 231a. DOI: 10.1016/j.bpj.2013.11.1350.
  • Abstract 4319: Lupus antibody-based cancer therapy.Hansen J, Chan G, Liu Y, Hegan D, Dalal S, Dray E, Kwon Y, Xu Y, Xu X, Peterson-Roth E, Geiger E, Liu Y, Gera J, Sweasy J, Sung P, Rockwell S, Nishimura R, Weisbart R, Glazer P. Abstract 4319: Lupus antibody-based cancer therapy. Cancer Research 2013, 73: 4319-4319. DOI: 10.1158/1538-7445.am2013-4319.
  • Abstract 1513: MLH1 silencing is caused by hypoxia through epigenetic regulation..Lu Y, Wajapeyee N, Turker M, Glazer P. Abstract 1513: MLH1 silencing is caused by hypoxia through epigenetic regulation.. Cancer Research 2013, 73: 1513-1513. DOI: 10.1158/1538-7445.am2013-1513.
  • Genetic Instability Induced by Hypoxic StressScanlon S, Glazer P. Genetic Instability Induced by Hypoxic Stress 2013, 151-181. DOI: 10.1007/978-1-4614-6280-4_8.
  • A Rare Cell-penetrating Anti-DNA Antibody Inhibits DNA Repair, Sensitizes Tumors To DNA-damaging Therapy, and is Synthetically Lethal to BRCA2-deficient Cancer CellsHansen J, Chan G, Liu Y, Gera J, Sweasy J, Sung P, Rockwell S, Nishimura R, Weisbart R, Glazer P. A Rare Cell-penetrating Anti-DNA Antibody Inhibits DNA Repair, Sensitizes Tumors To DNA-damaging Therapy, and is Synthetically Lethal to BRCA2-deficient Cancer Cells International Journal Of Radiation Oncology • Biology • Physics 2012, 84: s163. DOI: 10.1016/j.ijrobp.2012.07.422.
  • Vorinostat, a Histone Deacetylase Inhibitor, in Combination with Thoracic Radiotherapy in Advanced Non-small Cell Lung Cancer: A Dose Escalation StudyDecker R, Gettinger S, Glazer P, Wilson L. Vorinostat, a Histone Deacetylase Inhibitor, in Combination with Thoracic Radiotherapy in Advanced Non-small Cell Lung Cancer: A Dose Escalation Study International Journal Of Radiation Oncology • Biology • Physics 2011, 81: s574-s575. DOI: 10.1016/j.ijrobp.2011.06.1074.
  • Preclinical Studies of Onrigen in Combination with RadiationRockwell S, Liu Y, Glazer P, Sartorelli A. Preclinical Studies of Onrigen in Combination with Radiation International Journal Of Radiation Oncology • Biology • Physics 2011, 81: s752. DOI: 10.1016/j.ijrobp.2011.06.1249.
  • Abstract 3893: Mechanism of radiosensitization by inhibitors of poly(ADP-ribose) polymerase (PARP)Hegan D, Glazer P. Abstract 3893: Mechanism of radiosensitization by inhibitors of poly(ADP-ribose) polymerase (PARP) Cancer Research 2011, 71: 3893-3893. DOI: 10.1158/1538-7445.am2011-3893.
  • Abstract P6-04-04: Hypoxia Is Associated with Somatic Loss of BRCA1 Protein and Pathway Activity in Triple Negative Breast CancerNeumeister V, Li J, Lindner R, Sullivan C, Glazer P, Tuck D, Rimm D, Harris L. Abstract P6-04-04: Hypoxia Is Associated with Somatic Loss of BRCA1 Protein and Pathway Activity in Triple Negative Breast Cancer Cancer Research 2010, 70: p6-04-04-p6-04-04. DOI: 10.1158/0008-5472.sabcs10-p6-04-04.
  • Mechanism of Radiosensitization by Inhibitors of Poly (ADP-Ribose) Polymerase (PARP)Glazer P. Mechanism of Radiosensitization by Inhibitors of Poly (ADP-Ribose) Polymerase (PARP) International Journal Of Radiation Oncology • Biology • Physics 2010, 78: s87-s88. DOI: 10.1016/j.ijrobp.2010.07.234.
  • Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinomaScanlon S, Hegan D, Sulkowski P, Glazer P. Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma Oncotarget 2010, 5: 2-2. DOI: 10.18632/oncotarget.23445.
  • Abstract 1969: Inhibition of poly(ADP-ribose) polymerase downregulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130Hegan D, Lu Y, Stachelek G, Crosby M, Bindra R, Glazer P. Abstract 1969: Inhibition of poly(ADP-ribose) polymerase downregulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130 Cancer Research 2010, 70: 1969-1969. DOI: 10.1158/1538-7445.am10-1969.
  • Abstract 2185: Identification of novel compounds that preferentially kill repair deficient cells using high-throughput screeningPeterson-Roth E, Abriola L, Merkel J, Glazer P. Abstract 2185: Identification of novel compounds that preferentially kill repair deficient cells using high-throughput screening Cancer Research 2010, 70: 2185-2185. DOI: 10.1158/1538-7445.am10-2185.
  • Abstract C21: Hypoxia-induced down-regulation of BRCA1 nuclear protein in human breast cancer tissuesLi J, Sullivan C, Numeister V, Rimm D, Glazer P, Harris L. Abstract C21: Hypoxia-induced down-regulation of BRCA1 nuclear protein in human breast cancer tissues Molecular Cancer Therapeutics 2009, 8: c21-c21. DOI: 10.1158/1535-7163.targ-09-c21.
  • Targeting Base Excision Repair to Potentiate Cancer TherapyGlazer P, Stachelek G, Dalal S, Sweasy J. Targeting Base Excision Repair to Potentiate Cancer Therapy International Journal Of Radiation Oncology • Biology • Physics 2009, 75: s21. DOI: 10.1016/j.ijrobp.2009.07.071.
  • The Aberrant Expression of Beta-catenin in Esophageal Squamous Cell Cancer (ESCC) in Northeastern IranMani S, Moradi A, Abdolahi N, Martel M, Semnani S, Glazer P, Mani A. The Aberrant Expression of Beta-catenin in Esophageal Squamous Cell Cancer (ESCC) in Northeastern Iran International Journal Of Radiation Oncology • Biology • Physics 2007, 69: s309-s310. DOI: 10.1016/j.ijrobp.2007.07.1366.
  • Co-Repression of Mismatch Repair Gene Expression by Hypoxia in Cancer Cells: Role of the Myc/Max NetworkBindra R, Glazer P. Co-Repression of Mismatch Repair Gene Expression by Hypoxia in Cancer Cells: Role of the Myc/Max Network International Journal Of Radiation Oncology • Biology • Physics 2007, 69: s613. DOI: 10.1016/j.ijrobp.2007.07.1928.
  • 86 Complex Regulation of BRCA1 in Response to Hypoxic StressBindra R, Gibson S, Crosby M, Glazer P. 86 Complex Regulation of BRCA1 in Response to Hypoxic Stress International Journal Of Radiation Oncology • Biology • Physics 2006, 66: s50. DOI: 10.1016/j.ijrobp.2006.07.116.
  • 708. Gene Targeting with Triplex-Forming Oligonucletides in the Pyrimidine MotifKalish J, Knauert M, Hegan D, Glazer P. 708. Gene Targeting with Triplex-Forming Oligonucletides in the Pyrimidine Motif Molecular Therapy 2006, 13: s273-s274. DOI: 10.1016/j.ymthe.2006.08.787.
  • 1031. Improved Intranuclear Delivery of PNA- Peptide Conjugates Designed for Chromosomal Gene TargetingRogers F, Glazer P. 1031. Improved Intranuclear Delivery of PNA- Peptide Conjugates Designed for Chromosomal Gene Targeting Molecular Therapy 2006, 13: s396. DOI: 10.1016/j.ymthe.2006.08.1126.
  • Peptide Nucleic Acids as Agents to Modify Target Gene Expression and FunctionWang G, Glazer P. Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function 2006, 223-235. DOI: 10.1007/0-387-32956-0_14.
  • 89. Gene Targeting of β_Globin IVS2 Using Sequence_Specific Peptide Nucleic AcidsKuan J, Kole R, Nielsen P, Glazer P. 89. Gene Targeting of β_Globin IVS2 Using Sequence_Specific Peptide Nucleic Acids Molecular Therapy 2006, 13: s37. DOI: 10.1016/j.ymthe.2006.08.107.
  • 1030. Pyrazolo[3,4-d]Pyrimidine Guanine Base Substitution in Triplex Forming Oligonucleotides Improves Target Specificity and Chromosomal MutagenesisChin J, Chin J, Lloyd J, Lloyd J, Rogers F, Glazer P. 1030. Pyrazolo[3,4-d]Pyrimidine Guanine Base Substitution in Triplex Forming Oligonucleotides Improves Target Specificity and Chromosomal Mutagenesis Molecular Therapy 2006, 13: s396. DOI: 10.1016/j.ymthe.2006.08.1125.
  • Dysregulation of BRCAL in HypoxiaGlazer P, Bindra R. Dysregulation of BRCAL in Hypoxia International Journal Of Radiation Oncology • Biology • Physics 2005, 63: s145. DOI: 10.1016/j.ijrobp.2005.07.247.
  • 67 Expression of DNA-dsb repair proteins is altered under hypoxia in prostate cancer cellsBristow R, Meng A, Jalali F, Hedley D, Nichol T, Sweet J, Milosevic M, Bindra R, Glazer P. 67 Expression of DNA-dsb repair proteins is altered under hypoxia in prostate cancer cells Radiotherapy And Oncology 2005, 76: s20-s21. DOI: 10.1016/s0167-8140(05)80228-2.
  • Targeted Gene Modification Using Triplex-Forming OligonucleotidesKuan J, Glazer P. Targeted Gene Modification Using Triplex-Forming Oligonucleotides 2004, 0: 173-194. DOI: 10.1385/1-59259-761-0:173.
  • Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cellsGlazer P, Bindra R, Schaffer P, Bristow R, Hedley D. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells International Journal Of Radiation Oncology • Biology • Physics 2004, 60: s193. DOI: 10.1016/j.ijrobp.2004.06.131.
  • Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cellsGLAZER P, BINDRA R, SCHAFFER P, BRISTOW R, HEDLEY D. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells International Journal Of Radiation Oncology • Biology • Physics 2004, 60: s193-s193. DOI: 10.1016/s0360-3016(04)01188-5.
  • Targeted Genome Modification Via Triple Helix FormationRogers F, Glazer P. Targeted Genome Modification Via Triple Helix Formation 2004, 27-43. DOI: 10.1007/978-1-59259-777-2_3.
  • Peptide nucleic acids as agents to modify target gene expression and functionWang G, Glazer P. Peptide nucleic acids as agents to modify target gene expression and function International Journal Of Peptide Research And Therapeutics 2003, 10: 335-345. DOI: 10.1007/s10989-004-4903-0.
  • Over-expression of the DNA mismatch repair factor, PMS2, confers ionizing radiation resistance and hypermutabilityGlazer P, Narayanan L, Liskay M, Campisi D. Over-expression of the DNA mismatch repair factor, PMS2, confers ionizing radiation resistance and hypermutability International Journal Of Radiation Oncology • Biology • Physics 2002, 54: 51-52. DOI: 10.1016/s0360-3016(02)03145-0.
  • ATM-dependent expression of the IGF-I receptor in a pathway regulating radiation responseGlazer P, Peretz S, Jensen R, Gibson S. ATM-dependent expression of the IGF-I receptor in a pathway regulating radiation response International Journal Of Radiation Oncology • Biology • Physics 2001, 51: 55. DOI: 10.1016/s0360-3016(01)01923-x.
  • Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshiftsAndrew S, Xu X, Baross-Francis A, Narayanan L, Milhausen K, Liskay R, Jirik F, Glazer P. Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts Carcinogenesis 2000, 21: 1291-1296. DOI: 10.1093/carcin/21.5.291.
  • Better than the real thing: peptide nucleic acids Peptide Nucleic Acids: Protocols and Applications edited by Peter E. Nielsen and Michael EgholmGlazer P. Better than the real thing: peptide nucleic acids Peptide Nucleic Acids: Protocols and Applications edited by Peter E. Nielsen and Michael Egholm Trends In Genetics 2000, 16: 278. DOI: 10.1016/s0168-9525(00)01994-6.
  • DNA Repair Protocols: Eukaryotic SystemsGlazer P. DNA Repair Protocols: Eukaryotic Systems Radiation Research 2000, 153: 241-242. DOI: 10.1667/0033-7587(2000)153[0241:drpes]2.0.co;2.
  • Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pHGlazer P, Yuan J, Rockwell S, Narayanan L. Diminished DNA repair and elevated mutagenesis in mammalian cells exposed to hypoxia and low pH International Journal Of Radiation Oncology • Biology • Physics 2000, 48: 288. DOI: 10.1016/s0360-3016(00)80378-8.
  • The influence of the DNA mismatch repair gene, Pms2, on the celluar response to ionizing radiation at low dose ratesZeng M, Narayanan L, Glazer P. The influence of the DNA mismatch repair gene, Pms2, on the celluar response to ionizing radiation at low dose rates International Journal Of Radiation Oncology • Biology • Physics 2000, 48: 287. DOI: 10.1016/s0360-3016(00)80376-4.
  • 93 The germline p53 13964 gc mutation confers resistance to radiation in familial breast cancer patientsTurner B, Lehman T, Modali R, Carbone C, Bishop L, Curran W, Glazer P, Haffty B. 93 The germline p53 13964 gc mutation confers resistance to radiation in familial breast cancer patients International Journal Of Radiation Oncology • Biology • Physics 1999, 45: 195. DOI: 10.1016/s0360-3016(99)90111-6.
  • 156 Cyclin D1 expression mediates sensitivity in ataxia telangiectasia and breast cancerFritzell J, Glazer P, Haffty B, Gumbs A, Wang L, Carter D, Musgrove E, Curran W, Sutherland R, Turner B. 156 Cyclin D1 expression mediates sensitivity in ataxia telangiectasia and breast cancer International Journal Of Radiation Oncology • Biology • Physics 1999, 45: 228. DOI: 10.1016/s0360-3016(99)90174-8.
  • 105 Tumor hypoxia induces and selects for overexpression of the igf-i receptor: Implications for tumor progression and radioresistancePeretz S, Kim C, Rockwell S, Baserga R, Glazer P. 105 Tumor hypoxia induces and selects for overexpression of the igf-i receptor: Implications for tumor progression and radioresistance International Journal Of Radiation Oncology • Biology • Physics 1999, 45: 201. DOI: 10.1016/s0360-3016(99)90123-2.
  • Genome Modification by Triplex-Forming OligonucleotidesVasquez K, Glazer P. Genome Modification by Triplex-Forming Oligonucleotides 1999, 2: 167-179. DOI: 10.1007/978-1-4615-5177-5_13.
  • 154 Role of DNA mismatch repair in the cell response to ionizing radiationZeng M, Narayanan L, Xu S, Liskay M, Glazer P. 154 Role of DNA mismatch repair in the cell response to ionizing radiation International Journal Of Radiation Oncology • Biology • Physics 1999, 45: 227. DOI: 10.1016/s0360-3016(99)90172-4.
  • Elevated frequency of germline BRCA1/BRCA2 gene mutations in locally recurrent breast cancer patients following lumpectomy and radiation therapy: Implications for breast conserving management in affected patientsTurner B, Harrold E, Gumbs A, Matloff E, Ward B, Thomas A, Glazer P, Haffty B. Elevated frequency of germline BRCA1/BRCA2 gene mutations in locally recurrent breast cancer patients following lumpectomy and radiation therapy: Implications for breast conserving management in affected patients International Journal Of Radiation Oncology • Biology • Physics 1998, 42: 179. DOI: 10.1016/s0360-3016(98)80210-1.
  • Role of DNA mismatch repair in response to ionizing radiationGlazer P, Fritzell J, Narayanan L. Role of DNA mismatch repair in response to ionizing radiation International Journal Of Radiation Oncology • Biology • Physics 1998, 42: 154. DOI: 10.1016/s0360-3016(98)80160-0.
  • 1 The regulation of ipsilateral breast tumor recurrence after lumpectomy and radiation therapy by the transcription factors p53 and AP2Turner B, Glazer P, Gumbs A, Kaplan L, Maher M, Hurst H, Carter D, Williams T, Haffty B. 1 The regulation of ipsilateral breast tumor recurrence after lumpectomy and radiation therapy by the transcription factors p53 and AP2 International Journal Of Radiation Oncology • Biology • Physics 1997, 39: 135. DOI: 10.1016/s0360-3016(97)80558-5.
  • Targeted Mutagenesis Mediated by the Triple Helix FormationGlazer P, Wang G, Havre P, Gunther E. Targeted Mutagenesis Mediated by the Triple Helix Formation 1996, 57: 109-118. DOI: 10.1385/0-89603-332-5:109.
  • 41 Insulin growth factor-1 receptor (IGF-1R) expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control studyTurner B, Haffty B, Carter D, Gumbs A, Naryanan L, Baserga R, Glazer P. 41 Insulin growth factor-1 receptor (IGF-1R) expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study International Journal Of Radiation Oncology • Biology • Physics 1996, 36: 179. DOI: 10.1016/s0360-3016(97)85382-5.
  • Distinctive spectrum of point mutations in x-ray treated mouse cells: Implications for DNA damage and repair pathwaysGlazer P, Yuan J, Yeasky T, Rhee M. Distinctive spectrum of point mutations in x-ray treated mouse cells: Implications for DNA damage and repair pathways International Journal Of Radiation Oncology • Biology • Physics 1994, 30: 237-238. DOI: 10.1016/0360-3016(94)90771-4.
  • Mismatch Repair in Mammalian Cells: Approaches to the in Vitro Study of DNA Mismatch Correction ReactionsSummers W, Glazer P. Mismatch Repair in Mammalian Cells: Approaches to the in Vitro Study of DNA Mismatch Correction Reactions 1989, 255-261. DOI: 10.1007/978-1-4684-1327-4_24.
  • DNA mismatch repair detected in human cell extractsGlazer P, Sarkar S, Chisholm G, Summers W. DNA mismatch repair detected in human cell extracts Molecular And Cellular Biology 1987, 7: 218-224. DOI: 10.1128/mcb.7.1.218-224.1987.