Education and qualifications:
2009 – 2011
PGC, Academic Practice, University of Surrey, Guildford, Surrey, UK
1989 – 1994
PhD, Molecular Biology and Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
1991 – 1993
Doctoral research, Institute Curie, Paris, France
1984 – 1988
BSc, Biological Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Lecturer in DNA Damage and Ageing/Toxicology (University of Surrey)
2008 – 2009
Research fellow (St. George’s University of London)
2001 – 2008
Research scientist (Massachusetts Institute of Technology, Cambridge, USA)
1999 – 2000
Instructor (UT Southwestern Medical Center, Dallas, USA)
1995 – 1998
Post-doctoral fellow (UT Southwestern Medical Center, Dallas, USA)
Summary and Research Vision
The overarching theme of my research has been the study of cellular responses to stress and their importance in the pathogenesis and therapeutics of cancer and other chronic diseases. In particular, my work has focused on alkylating agents, a ubiquitous family of reactive chemicals that are cytotoxic and mutagenic and pose significant threats to human health but are also commonly used systemically in the clinic as cancer chemotherapeutic agents.
My research has uncovered novel relationships between stress pathways and cellular metabolism that are important in the response to alkylating agents. The long-term goal of my research is to use knowledge from our studies to define new mechanisms of stress response and to develop therapies to treat human disease.
Postgraduate research supervision
Dr. Eirini Martinou - PhD student
Thomas "Tom" Cox - PhD student
Abbey Pearson - MSci in Biochemistry
Postgraduate research supervision
Amy Barber, PhD awarded
Anzhalika Talstaya, PhD awarded
Nikunj Shah, MD awarded
Clara Forrer Charlier, PhD awarded
Abdullah Aljohani, PhD awarded
Fahad Alhumaydhi, PhD awarded
Styliani Totti, PhD student, awarded
Eleanor Healing, PhD awarded
Natalie Mayhead, PhD awarded
Larissa Milano, PhD awarded
Matshedisho Zachariah, PhD awarded
Balqees Issa Mohammed Al Yahyaei, PhD awarded
Ali Jbbar, PhD awarded
Rati Mohan, PhD awarded
Noura Alasmael, PhD awarded
BMS1025 - Cell Biology
BMS3063 - Cancer: Pathogenesis and Therapeutics
BMS3099 - Mechanistic Toxicology and Pharmacokinetics
BMSM024 - Developing as a Scientist: Advanced Techniques in Biochemistry
Courses I teach on
More than 15% of cancer deaths worldwide are associated with underlying infections or inflammatory conditions, therefore understanding how inflammation contributes to cancer etiology is important for both cancer prevention and treatment. Inflamed tissues are known to harbor elevated etheno-base (ε-base) DNA lesions induced by the lipid peroxidation that is stimulated by reactive oxygen and nitrogen species (RONS) released from activated neutrophils and macrophages. Inflammation contributes to carcinogenesis in part via RONS-induced cytotoxic and mutagenic DNA lesions, including ε-base lesions. The mouse alkyl adenine DNA glycosylase (AAG, also known as MPG) recognizes such base lesions, thus protecting against inflammation-associated colon cancer. Two other DNA repair enzymes are known to repair ε-base lesions, namely ALKBH2 and ALKBH3; thus, we sought to determine whether these DNA dioxygenase enzymes could protect against chronic inflammation-mediated colon carcinogenesis. Using established chemically induced colitis and colon cancer models in mice, we show here that ALKBH2 and ALKBH3 provide cancer protection similar to that of the DNA glycosylase AAG. Moreover, Alkbh2 and Alkbh3 each display apparent epistasis with Aag. Surprisingly, deficiency in all 3 DNA repair enzymes confers a massively synergistic phenotype, such that animals lacking all 3 DNA repair enzymes cannot survive even a single bout of chemically induced colitis.
The cytotoxicity of radiotherapy and chemotherapy can be enhanced by modulating DNA repair. PARP is a family of enzymes required for an efficient base-excision repair of DNA single-strand breaks and inhibition of PARP can prevent the repair of these lesions. The current study investigates the trimodal combination of ABT-888, a potent inhibitor of PARP1-2, ionizing radiation and temozolomide(TMZ)-based chemotherapy in glioblastoma (GBM) cells.
O6-methylguanine DNA methyltransferase (MGMT) suppresses mutations and cell death that result from alkylation damage. MGMT expression is lost by epigenetic silencing in a variety of human cancers including nearly half of sporadic colorectal cancers, suggesting that this loss maybe causal. Using mice with a targeted disruption of the Mgmt gene, we tested whether Mgmt protects against azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF), against AOM and dextran sulfate sodium (DSS)-induced colorectal adenomas and against spontaneous intestinal adenomas in ApcMin mice. We also examined the genetic interaction of the Mgmt null gene with a DNA mismatch repair null gene, namely Msh6. Both Mgmt and Msh6 independently suppress AOM-induced ACF, and combination of the two mutant alleles had a multiplicative effect. This synergism can be explained entirely by the suppression of alkylation-induced apoptosis when Msh6 is absent. In addition, following AOM+DSS treatment Mgmt protected against adenoma formation to the same degree as it protected against AOM-induced ACF formation. Finally, Mgmt deficiency did not affect spontaneous intestinal adenoma development in ApcMin/+ mice, suggesting that Mgmt suppresses intestinal cancer associated with exogenous alkylating agents, and that endogenous alkylation does not contribute to the rapid tumor development seen in ApcMin/+ mice.
Background: Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological contexts in which lysosomal genes are coordinately regulated and to identify transcription factors involved in this control.Results: As transcription factors and their target genes are often co-regulated, we performed meta-analyses of array-based expression data to identify regulators whose mRNA profiles are highly correlated with those of a core set of lysosomal genes. Among the ~50 transcription factors that rank highest by this measure, 65% are involved in differentiation or development, and 22% have been implicated in interferon signaling. The most strongly correlated candidate was Stat6, a factor commonly activated by interleukin-4 (IL-4) or IL-13. Publicly available chromatin immunoprecipitation (ChIP) data from alternatively activated mouse macrophages show that lysosomal genes are overrepresented among Stat6-bound targets. Quantification of RNA from wild-type and Stat6-deficient cells indicates that Stat6 promotes the expression of over 100 lysosomal genes, including hydrolases, subunits of the vacuolar H+ ATPase and trafficking factors. While IL-4 inhibits and activates different sets of lysosomal genes, Stat6 mediates only the activating effects of IL-4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL-4.Conclusions: The current data establish Stat6 as a broadly acting regulator of lysosomal gene expression in mouse macrophages. Other regulators whose expression correlates with lysosomal genes suggest that lysosome function is frequently re-programmed during differentiation, development and interferon signaling. © 2013 Brignull et al.; licensee BioMed Central Ltd.
Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative breast cancer results in poor survival. An area of increasing interest is metabolic reprogramming, whereby drug-induced alterations in the metabolic landscape of a tumour slow tumour growth and/or increase sensitivity to existing therapeutics. Nuclear receptors are transcription factors central to the expression of metabolic and transport proteins, and thus represent potential targets for metabolic reprogramming. We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA-MB-231 and MDA-MB-468 (triple negative). Furthermore, we show that the mechanism of cell death is predominantly through the intrinsic apoptotic pathway. Finally, we demonstrate that FXR agonists do not stimulate migration in breast cancer cell lines, an important potential adverse effect. Together, our data support the continued examination of FXR agonists as a novel class of therapeutics for the treatment of breast cancer.
DNA alkylation damage is repaired by base excision repair (BER) initiated by alkyladenine DNA glycosylase (AAG). Despite its role in DNA repair, AAG-initiated BER promotes cytotoxicity in a process dependent on poly (ADP-ribose) polymerase-1 (PARP-1); a NAD+-consuming enzyme activated by strand break intermediates of the AAG-initiated repair process. Importantly, PARP-1 activation has been previously linked to impaired glycolysis and mitochondrial dysfunction. However, whether alkylation affects cellular metabolism in the absence of AAG-mediated BER initiation is unclear. To address this question, we temporally profiled repair and metabolism in wild-type and Aag−I− cells treated with the alkylating agent methyl methanesulfonate (MMS). We show that, although Aag−I− cells display similar levels of alkylation-induced DNA breaks as wild type, PARP-1 activation is undetectable in AAG-deficient cells. Accordingly, Aag−I− cells are protected from MMS-induced NAD+ depletion and glycolysis inhibition. MMS-induced mitochondrial dysfunction, however, is AAG-independent. Furthermore, treatment with FK866, a selective inhibitor of the NAD+ salvage pathway enzyme nicotinamide phosphoribosyltransferase (NAMPT), synergizes with MMS to induce cytotoxicity and Aag−I− cells are resistant to this combination FK866 and MMS treatment. Thus, AAG plays an important role in the metabolic response to alkylation that could be exploited in the treatment of conditions associated with NAD+ dysregulation.
Objective The aim of this study was to examine DNA ligase activity and expression of DNA damage response pathway (DDR) genes in patients with stable angina (SA) and non-ST elevation myocardial infarction (NSTEMI) and determine whether they correlate with plaque morphology. Background Patients with coronary artery disease (CAD) have evidence of deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear cells (PBMCs). It is unclear whether this represents excess damage or defective DNA repair activity. Methods DNA ligase activity and the expression of 22 DDR genes were measured in PBMCs of patients (both SA (n = 47) and NSTEMI (n = 42)) and in age and gender-matched controls (n = 35). Target lesion anatomical assessment was undertaken with frequency domain optical coherent tomography. Results DNA ligase activity was different across the three groups of patients (control = 119 ± 53, NSTEMI = 115.6 ± 85.1, SA = 81 ± 55.7 units/g of nuclear protein; ANOVA p = 0.023). Pair wise comparison demonstrated that this significance is due to differences between the control and SA patients (p = 0.046). Genes involved in double strand break repair and nucleotide excision repair pathways were differentially expressed in patients with SA and NSTEMI. In SA patients, fibrocalcific plaques were strongly associated with GTSE1, DDB1, MLH3 and ERCC1 expression. By contrast, in NSTEMI patients the strongest association was observed between fibrous plaques and ATM and XPA expression. Conclusion PBMCs from patients with CAD exhibit differences in DNA ligase activity and expression of DDR genes. Expression levels of certain DDR genes are strongly associated with plaque morphology and may play a role in plaque development and progression.
Selenium is an essential trace element important for human health. A balanced intake is, however, crucial to maximize the health benefits of selenium. At physiological concentrations, selenium mediates antioxidant, anti‐inflammatory, and pro‐survival actions. However, supra‐nutritional selenium intake was associated with increased diabetes risk leading potentially to endothelial dysfunction, the initiating step in atherosclerosis. High selenium causes apoptosis in cancer cells via endoplasmic reticulum (ER) stress, a mechanism also implicated in endothelial dysfunction. Nonetheless, whether ER stress drives selenium‐induced endothelial dysfunction, remains unknown. Here, we investigated the effects of increasing concentrations of selenium on endothelial cells. High selenite reduced nitric oxide bioavailability and impaired angiogenesis. High selenite also induced ER stress, increased reactive oxygen species (ROS) production, and apoptosis. Pretreatment with the chemical chaperone, 4‐phenylbutyrate, prevented the toxic effects of selenium. Our findings support a model where high selenite leads to endothelial dysfunction through activation of ER stress and increased ROS production. These results highlight the importance of tailoring selenium supplementation to achieve maximal health benefits and suggest that prophylactic use of selenium supplements as antioxidants may entail risk
DNA repair capacity varies greatly between individuals, and evidence has begun to link this variation to cancer risk, obesity and related chronic diseases. There is also emerging evidence that dietary components can affect DNA repair, but research to date has been restricted by methods for measuring DNA repair. This study made use of newly developed microplate-based assays for the direct determination of DNA repair enzyme activities. Lipid loading of the HepG2 human hepatocellular carcinoma cell line was employed as a model to test the hypothesis that hepatic steatosis affects DNA repair activity via induction of oxidative stress.
Colorectal cancer (CRC) is prevalent worldwide, and treatment often involves surgery and genotoxic chemotherapy. DNA repair mechanisms, such as base excision repair (BER) and mismatch repair (MMR), may not only influence tumour characteristics and prognosis but also dictate chemotherapy response. Defective MMR contributes to chemoresistance in colorectal cancer. Moreover, BER affects cellular survival by repairing genotoxic base damage in a process that itself can disrupt metabolism. In this study, we characterized BER and MMR gene expression in colorectal tumours and the association between this repair profile with patients’ clinical and pathological features. In addition, we exploited the possible mechanisms underlying the association between altered DNA repair, metabolism and response to chemotherapy. Seventy pairs of sporadic colorectal tumour samples and adjacent non-tumour mucosal specimens were assessed for BER and MMR gene and protein expression and their association with pathological and clinical features. MMR-deficient colon cancer cells (HCT116) transiently overexpressing MPG or XRCC1 were treated with 5-FU or TMZ and evaluated for viability and metabolic intermediate levels. Increase in BER gene and protein expression is associated with more aggressive tumour features and poor pathological outcomes in CRC. However, tumours with reduced MMR gene expression also displayed low MPG, OGG1 and PARP1 expression. Imbalancing BER by overexpression of MPG, but not XRCC1, sensitises MMR-deficient colon cancer cells to 5-FU and TMZ and leads to ATP depletion and lactate accumulation. MPG overexpression alters DNA repair and metabolism and is a potential strategy to overcome 5-FU chemotherapeutic resistance in MMR-deficient CRC.
Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering point that three-dimensional cultures can reflect the in vivo tumour micro-environment and can guarantee a physiological distribution of oxygen, nutrients and drugs, therefore, being promising low cost tools for therapy development. In this work we review crucial elements, i.e., structural and environmental, that should be considered for an accurate design of an ex vivo platform for studies of pancreatic cancer. Furthermore, we propose environmental stress response biomarkers as platform readouts for the efficient control and further prediction of the pancreatic cancer response to the environmental and treatment input.
Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.
DNA repair is essential for the maintenance of genomic integrity, and evidence suggest that interindividual variation in DNA repair efficiency maycontribute to disease risk. However, robust assays suitable for quantitative determination of DNA repair capacity in large cohort and clinical trials are needed to evaluate these apparent associations fully. We describe here a set of microplate-based oligonucleotide assays for high-throughput, non-radioactiveand quantitative determination of repair enzyme activity at individual steps and over multiple steps of the DNA base excision repair pathway. The assays are highly sensitive: using HepG2 nuclear extract, enzyme activities were quantifiable at concentrationsof 0.0002 to 0.181 g per reaction, depending on the enzyme being measured. Assay coefficients of variation are comparable with other microplate-based assays. The assay format requires no specialist equipment and has the potential to be extended for analysis of a wide range of DNA repair enzyme activities. As such, these assays hold considerable promise for gaining new mechanistic insights into how DNA repair is related to individual genetics, disease status or progression and other environmental factors and investigating whether DNA repair activities can be used a biomarker of disease risk.
Healing, Eleanor, Charlier, Clara. F, Meira, Lisie and Elliott, Ruan (2019) A panel of colorimetric assays to measure enzymatic activity in the base excision DNA repair pathway Nucleic Acids Research, 47 (11), e61.
Leguisamo, NM, Gloria, HC, Kalil, AN, Martins, TV, Azambuja, DB, Meira, Lisiane and Saffi, J (2017) Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy Oncotarget. pp. 1-16.
Totti, Styliani, Vernardis, SI, Meira, Lisiane, Pérez-Mancera, PA, Costello, E, Greenhalf, W, Palmer, D, Neoptolemos, J, Mantalaris, A and Velliou, Eirini (2017) Designing a bio-inspired bio-mimetic in vitro system for the optimisation of ex vivo studies of pancreatic cancer Drug Discovery Today, 22 (4). pp. 690-701.
Alasmael, N, Mohan, R, Meira, LB, Swales, KE and Plant, NJ (2015) Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential Cancer Letters.
Meira, LB, Calvo, JA, Shah, D, Klapacz, J, Moroski-Erkul, CA, Bronson, RT and Samson, LD (2014) Repair of endogenous DNA base lesions modulate lifespan in mice DNA REPAIR, 21. pp. 78-86.
Brignull, LM, Czimmerer, Z, Saidi, H, Daniel, B, Villela, I, Bartlett, NW, Johnston, SL, Meira, LB, Nagy, L and Nohturfft, A (2013) Reprogramming of lysosomal gene expression by interleukin-4 and Stat6 BMC GENOMICS, 14, ARTN 8.
Bordin, DL, Lima, M, Lenz, G, Saffi, J, Meira, LB, Mesange, P, Soares, DG, Larsen, AK, Escargueil, AE and Henriques, JAP (2013) DNA alkylation damage and autophagy induction MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 753 (2). pp. 91-99.
Polycarpou, E, Meira, LB, Carrington, S, Tyrrell, E, Modjtahedi, H and Carew, MA (2013) Resveratrol 3-O-D-glucuronide and resveratrol 4 '-O-D-glucuronide inhibit colon cancer cell growth: Evidence for a role of A3 adenosine receptors, cyclin D1 depletion, and G1 cell cycle arrest MOLECULAR NUTRITION & FOOD RESEARCH, 57 (10). pp. 1708-1717.
Calvo, JA, Moroski-Erkul, CA, Lake, A, Eichinger, LW, Shah, D, Jhun, I, Limsirichai, P, Bronson, RT, Christiani, DC, Meira, LB and Samson, LD (2013) Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1 PLOS GENETICS, 9 (4), ARTN e.
Barazzuol, L, Jena, R, Burnet, NG, Meira, LB, Jeynes, JC, Kirkby, KJ and Kirkby, NF (2013) Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma. Radiat Oncol, 8.
Calvo, JA, Meira, LB, Lee, CY, Moroski-Erkul, CA, Abolhassani, N, Taghizadeh, K, Eichinger, LW, Muthupalani, S, Nordstrand, LM, Klungland, A and Samson, LD (2012) DNA repair is indispensable for survival after acute inflammation. The Journal of Clinical Investigation, 122 (7). pp. 2680-2689.
Villela, I, Heidenreich, B, Cheema, M, di Martino, T, Samson, LD and Meira, LB (2011) Dissecting the mechanism of DNA damage induced photoreceptor cell death TOXICOLOGY, 290 (2-3). p. 143.
Kisby, GE, Fry, RC, Lasarev, MR, Bammler, TK, Beyer, RP, Churchwell, M, Doerge, DR, Meira, LB, Palmer, VS, Ramos-Crawford, A-L, Ren, X, Sullivan, RC, Kavanagh, TJ, Samson, LD, Zarbl, H and Spencer, PS (2011) The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner PLOS ONE, 6 (6), ARTN e.
Unnikrishnan, A, Raffoul, JJ, Patel, HV, Prychitko, TM, Anyangwe, N, Meira, LB, Friedberg, EC, Cabelof, DC and Heydari, AR (2009) Oxidative stress alters base excision repair pathway and increases apoptotic response in apurinic/apyrimidinic endonuclease 1/redox factor-1 haploinsufficient mice FREE RADICAL BIOLOGY AND MEDICINE, 46 (11). pp. 1488-1499.
Bugni, JM, Meira, LB and Samson, LD (2009) Alkylation-induced colon tumorigenesis in mice deficient in the Mgmt and Msh6 proteins ONCOGENE, 28 (5). pp. 734-741.
Meira, LB, Moroski-Erkul, CA, Green, SL, Calvo, JA, Bronson, RT, Shah, D and Samson, LD (2009) Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice. Proc Natl Acad Sci U S A, 106 (3). pp. 888-893.
Klapacz, J, Meira, LB, Luchetti, DG, Calvo, JA, Bronson, RT, Edelmann, W and Samson, LD (2009) O-6-methylguanine-induced cell death involves exonuclease 1 as well as DNA mismatch recognition in vivo PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106 (2). pp. 576-581.
Maor-Shoshani, A, Meira, LB, Yang, X and Samson, LD (2008) 3-methyladenine DNA glycosylase ill important for cellular resistance to psoralen interstrand cross-links DNA REPAIR, 7 (8). pp. 1399-1406.
Meira, LB, Bugni, JM, Green, SL, Lee, C-W, Pang, B, Borenshtein, D, Rickman, BH, Rogers, AB, Moroski-Erkul, CA, McFaline, JL, Schauer, DB, Dedon, PC, Fox, JG and Samson, LD (2008) DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice JOURNAL OF CLINICAL INVESTIGATION, 118 (7). pp. 2516-2525.
Ringvoll, J, Moen, MN, Nordstrand, LM, Meira, LB, Pang, B, Bekkelund, A, Dedon, PC, Bjelland, S, Samson, LD, Falnes, PO and Klungland, A (2008) AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA CANCER RESEARCH, 68 (11). pp. 4142-4149.
Lingaraju, GM, Kartalou, M, Meira, LB and Samson, LD (2008) Substrate specificity and sequence-dependent activity of the Saccharomyces cerevisiae 3-methyladenine DNA glycosylase (Mag) DNA REPAIR, 7 (6). pp. 970-982.
Dong, L, Meira, LB, Hazra, TK, Samson, LD and Cao, W (2008) Oxanine DNA glycosylase activities in mammalian systems DNA REPAIR, 7 (1). pp. 128-134.
Longerich, S, Meira, L, Shah, D, Samson, LD and Storb, U (2007) Alkyladenine DNA glycosylase (Aag) in somatic hypermutation and class switch recombination DNA REPAIR, 6 (12). pp. 1764-1773.
Beyer, RP, Fry, RC, Lasarev, MR, McConnachie, LA, Meira, LB, Palmer, VS, Powell, CL, Ross, PK, Bammler, TK, Bradford, BU, Cranson, AB, Cunningham, ML, Fannin, RD, Higgins, GM, Hurban, P, Kayton, RJ, Kerr, KF, Kosyk, O, Lobenhofer, EK, Sieber, SO, Vliet, PA, Weis, BK, Wolfinger, R, Woods, CG, Freedman, JH, Linney, E, Kaufmann, WK, Kavanagh, TJ, Paules, RS, Rusyn, I, Samson, LD, Spencer, PS, Suk, W, Tennant, RJ and Zarbl, H (2007) Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses TOXICOLOGICAL SCIENCES, 99 (1). pp. 326-337.
Lee, CW, Rickman, B, Meira, LB, Samson, L and Fox, JG (2007) Base excision repair genes alkyl adenine DNA glycosylase (Aag) and O6-methylguanine DNA methyltransferase (Mgmt) suppresses Helicobacter pylori-associated inflammation and progression to cancer GASTROENTEROLOGY, 132 (4). A319-A319.
Friedberg, EC and Meira, LB (2006) Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage Version 7 DNA REPAIR, 5 (2). pp. 189-209.
Meira, LB, Burgis, NE and Samson, LD (2005) Base excision repair pp. 125-173.
Friedberg, EC and Meira, LB (2004) Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage (Version 6) DNA REPAIR, 3 (12). pp. 1617-1638.
Hitchcock, TM, Dong, L, Connor, EE, Meira, LB, Samson, LD, Wyatt, MD and Cao, WG (2004) Oxanine DNA glycosylase activity from mammalian alkyladenine glycosylase JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (37). pp. 38177-38183.
Raffoul, JJ, Cabelof, DC, Nakamura, J, Meira, LB, Friedberg, EC and Heydari, AR (2004) Apurinic/apyrimidinic endonuclease (APE/REF-1) haploinsufficient mice display tissue-specific differences in DNA polymerase beta-dependent base excision repair JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (18). pp. 18425-18433.
Ham, AJL, Engelward, BP, Koc, H, Sangaiah, R, Meira, LB, Samson, LD and Swenberg, JA (2004) New immunoaffinity-LC-MS/MS methodology reveals that Aag null mice are deficient in their ability to clear 1,N-6-etheno-deoxyadenosine DNA lesions from lung and liver in vivo DNA REPAIR, 3 (3). pp. 257-265.
Friedberg, EC and Meira, LB (2003) Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage Version 5 DNA REPAIR, 2 (5). pp. 501-530.
Meira, LB, Cheo, DL, Reis, AM, Chaij, N, Burns, DK, te Riele, H and Friedberg, EC (2002) Mice defective in the mismatch repair gene Msh2 show increased predisposition to UVB radiation-induced skin cancer (vol 1, pg 929, 2002) DNA REPAIR, 1 (12), PII S1568-. p. 1063.
Meira, LB, Cheo, DL, Reis, AM, Claij, N, Burns, DK, Riele, HT and Friedberg, EC (2002) Mice defective in the mismatch repair gene Msh2 show increased predisposition to UVB radiation-induced skin cancer DNA REPAIR, 1 (11), PII S1568-. pp. 929-934.
Meira, LB, Devaraj, S, Kisby, GE, Burns, DK, Daniel, RL, Hammer, RE, Grundy, S, Jialal, I and Friedberg, EC (2001) Heterozygosity for the mouse Apex gene results in phenotypes associated with oxidative stress CANCER RESEARCH, 61 (14). pp. 5552-5557.
Meira, LB, Reis, AMC, Cheo, DL, Nahari, D, Burns, DK and Friedberg, EC (2001) Cancer predisposition in mutant mice defective in multiple genetic pathways: uncovering important genetic interactions MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 477 (1-2). pp. 51-58.
Friedberg, EC and Meira, LB (2000) Database of mouse strains carrying targeted mutations in genes affecting cellular responses to DNA damage. Version 4 MUTATION RESEARCH-DNA REPAIR, 459 (4). pp. 243-274.
Meira, LB, Graham, JM, Greenberg, CR, Busch, DB, Doughty, ATB, Ziffer, DW, Coleman, DM, Savre-Train, I and Friedberg, EC (2000) Manitoba aboriginal kindred with original cerebro-oculo-facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene AMERICAN JOURNAL OF HUMAN GENETICS, 66 (4). pp. 1221-1228.
Graham, JM, Meira, LB, Greenberg, CR, Busch, DB, Doughty, ATB, Ziffer, DW, Coleman, DM, Savre-Train, I and Friedberg, EC (2000) Original COFS syndrome Manitoba Aboriginal kindred has a mutation in the Cockayne syndrome group B (CSB) gene PEDIATRIC RESEARCH, 47 (4). 81A-81A.
Friedberg, EC, Bond, JP, Burns, DK, Cheo, DL, Greenblatt, MS, Meira, LB, Nahari, D and Reis, AM (2000) Defective nucleotide excision repair in Xpc mutant mice and its association with cancer predisposition MUTATION RESEARCH-DNA REPAIR, 459 (2). pp. 99-108.
Reis, AM, Cheo, DL, Meira, LB, Greenblatt, MS, Bond, JP, Nahari, D and Friedberg, EC (2000) Genotype-specific Trp53 mutational analysis in ultraviolet B radiation-induced skin cancers in Xpc and Xpc Trp53 mutant mice CANCER RESEARCH, 60 (6). pp. 1571-1579.
Cheo, DL, Meira, LB, Burns, DK, Reis, AM, Issac, T and Friedberg, EC (2000) Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: Genotype-specific effects on cancer predisposition and pathology of tumors CANCER RESEARCH, 60 (6). pp. 1580-1584.
Graham, JM, Meira, LB, Greenberg, CR, Busch, D and Friedberg, EC (2000) Original COFS syndrome kindred from Manitoba has a mutation in the cockayne syndrome group B (CSB) gene. JOURNAL OF INVESTIGATIVE MEDICINE, 48 (1). 48A-48A.
Graham, JM, Meira, LB, Greenberg, CR, Jaspers, NGJ, Busch, D, Coleman, DM, Ziffer, DW and Friedberg, EC (1999) Original COFS syndrome Manitoba Aboriginal kindred has a mutation in the Cockayne syndrome group B (CSB) gene. AMERICAN JOURNAL OF HUMAN GENETICS, 65 (4). A299-A299.
Friedberg, EC and Meira, LB (1999) Database of mouse strains carrying targeted mutations in genes affecting cellular responses to DNA damage: version 3 MUTATION RESEARCH-DNA REPAIR, 433 (2). pp. 69-87.
Cheo, DL, Burns, DK, Meira, LB, Houle, JF and Friedberg, EC (1999) Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53(-/-) mice CANCER RESEARCH, 59 (4). pp. 771-775.
Friedberg, EC, Meira, LB and Cheo, DL (1998) Database of mouse strains carrying targeted mutations in genes affecting cellular responses to DNA damage. Version 2 MUTATION RESEARCH-DNA REPAIR, 407 (3). pp. 217-226.
Meira, LB, Cheo, DL, Hammer, RE, Burns, DK, Reis, A and Friedberg, EC (1997) Genetic interaction between HAP1/REF-1 and p53 NATURE GENETICS, 17 (2). p. 145.
Friedberg, EC, Meira, LB and Cheo, DL (1997) Database of mouse strains carrying targeted mutations in genes affecting cellular responses to DNA damage MUTATION RESEARCH-DNA REPAIR, 383 (2). pp. 183-188.
Cheo, DL, Ruven, HJT, Meira, LB, Hammer, RE, Burns, DK, Tappe, NJ, vanZeeland, AA, Mullenders, LHF and Friedberg, EC (1997) Characterization of defective nucleotide excision repair in XPC mutant mice MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 374 (1). pp. 1-9.
Cheo, DL, Meira, LB, Hammer, RE, Burns, DK, Doughty, ATB and Friedberg, EC (1996) Synergistic interactions between XPC and p53 mutations in double-mutant mice: Neural tube abnormalities and accelerated UV radiation-induced skin cancer CURRENT BIOLOGY, 6 (12). pp. 1691-1694.