Publication Highlights

SpheroidChip: Patterned Agarose Microwell Compartments Harboring HepG2 Spheroids are Compatible with Genotoxicity Testing. Christy Chao, Le P. Ngo, Bevin P. Engelward. ACS Biomater Sci Eng., 2020. In the news

Improved CometChip offers a better way to screen for chemical safety. Ngo LP, Owiti NA, Swartz C, Winters J, Su Y, Ge J, Xiong A, Han J, Recio L, Samson LD, Engelward BP. Sensitive CometChip assay for screening potentially carcinogenic DNA adducts by trapping DNA repair intermediates. Nucleic Acids Res. 2020 Feb 20;48(3):e13. In the news.

MicroColonyChip: A better way to measure cell survival. Ngo LP, Chan TK, Ge J, Samson LD, and Engelward BP. Microcolony size distribution assay enables high-throughput cell survival quantitation. Cell Reports. 2019 26:1668-1678. In the news and on the MIT Homepage

CometChip reveals that Colibactin from E. coli creates DNA interstrand crosslinks. Wilson MR, Jiang Y, Villalta PW, Stornetta A, Boudreau PD, Carrá A, Brennan CA, Chun E, Ngo L, Samson LD, Engelward BP, Garrett WS, Balbo S, Balskus EP. The human gut bacterial genotoxin colibactin alkylates DNA. Science. 2019 Feb 15;363(6428).

Demonstration that asthma causes DNA damage points to DNA repair as a susceptibility factor for asthma. Chan TK, Loh XY, Peh HY, Tan WNF, Tan WSD, Li N, Tay IJJ, Wong WSF, Engelward BP. House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs. J. Allergy Clin. Immunol. 2016 138:84-96.e1. In the news and on the MIT Homepage

An emerging role for DNA damaging agents in infectious disease: for S. pneumoniae, the ability to secrete genotoxic chemicals is a pathogenicity factor.
Rai P, Parrish M, Tay IJ, Li N, Ackerman S, He F, Kwang J, Chow VT, Engelward BP. Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells. Proc. Natl. Acad. Sci. USA. 2015 Jun 30;112(26):E3421-30. In the MIT News

Inflammation-induced cell proliferation acts synergistically with DNA damage to induce mutations.
Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP. Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genetics. 2015 Feb 3;11(2):e1004901. In the MIT News

Graduate Students Criss-Cross the Globe to Work Together: Collaboration between MIT and Thai Researchers enables Application of New Tools to address Global Problems in Public Health. Ge J, Prasongtanakij S, Wood DK, Weingeist DM, Fessler J, Navasummrit P, Ruchirawat M, and Engelward BP. CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells. J Vis Exp. 2014

Spontaneous levels of base excision repair shown to pressure homologous recombination in vivo, Kiraly O, Gong G, Roytman MD, Yamada Y, Samson LD, Engelward BP. DNA glycosylase activity and cell proliferation are key factors in modulating homologous recombination in vivo. Carcinogenesis. 2014 Aug 25. pii: bgu177.

Nanoparticles shown to be genotoxic, Watson C, Ge J, Cohen J, Pyrgiotakis G, Engelward BP, Demokritou P. High-throughput screening platform for engineered nanoparticle-mediated genotoxicity using CometChip technology. ACS Nano. 2014 Mar 25;8(3):2118-33. In the MIT News

Second generation mouse model enables studies of homologous recombination in a broad range of tissue types and reveals accumulation of recombination events in somatic stem cells. Sukup-Jackson MR, Kiraly O, Kay JE, Na L, Rowland EA, Winther KE, Chow DN, Kimoto T, Matsuguchi T, Jonnalagadda VS, Maklakova VI, Singh VR, Wadduwage DN, Rajapakse J, So PT, Collier LS, Engelward BP. Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS Genet. 2014 Jun5;10(6):e1004299. In the MIT news

CometChip enables high throughput screening of DNA double strand breaks. Weingeist DM, Ge J, Wood DK, Mutamba JT, Huang Q, Rowland EA, Yaffe MB, Floyd S, and Engelward BP. Single cell microarray enables high throughput evaluation of DNA double strand breaks and DNA repair inhibitors. Cell Cycle. 2013 Mar 15;12(6):907-15.
News and Views by Nickoloff J.A., Assaying DNA double-strand break induction and repair as fast as a speeding comet, Cell Cycle. 2013 12:1335-6.

Imaging approaches for suppression of light-induced DNA damage. Ge J, Wood DK, Weingeist DM, Prasongtanakig S, Navasumrit P, Ruchirawat M, Engelward BP. Standard fluorescent imaging of live cells is highly genotoxic. Cytometry A. 2013 Jun;83(6):552-60. Editorial by Tárnok A., Visualization can be harmful for live cells, Cytometry A., 2013 83:521-2.

MIT study suggests that at low dose-rate, radiation poses little risk to DNA. (also featured by MIT as “Best of 2012”) News of this study was dispersed to over 50 sites worldwide. Olipitz W, Wiktor-Brown D, Shuga J, Pang B, McFaline J, Lonkar P, Thomas A, Mutamba JT, Greenberger JS, Samson LD, Dedon PC, Yanch JC, Engelward BP. Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation. Environ Health Perspect. 2012 Aug;120(8):1130-6. In the news and on the MIT Homepage

Novel technology for high throughput analysis of DNA damage
Wood DK, Weingeist DM, Bhatia SN, Engelward BP. Single cell trapping and DNA damage analysis using microwell arrays. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10008-13. In the news and on the MIT Homepage

Burden of mutant cells is driven primarily by cell division in the pancreas
Wiktor-Brown DM, Kwon HS, Nam YS, So PT, Engelward BP. Integrated one- and two-photon imaging platform reveals clonal expansion as a major driver of mutation load. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10314-9. In the MIT news

Recombination mechanisms come to life with animations See Animations
Top 10 downloaded papers in DNA Repair for 2008-2011; Most highly cited article in 2012
Helleday T, Lo J, van Gent DC, Engelward BP. DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Repair (Amst). 2007 Jul 1;6(7):923-35.

Visualization of fluorescent recombinant cells reveals accumulation with age
Wiktor-Brown DM, Hendricks CA, Olipitz W, Engelward BP. Age-dependent accumulation of recombinant cells in the mouse pancreas revealed by in situ fluorescence imaging. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11862-7.

Indirect induction of homologous recombination is transmissible
Rugo RE, Almeida KH, Hendricks CA, Jonnalagadda VS, Engelward BP. A single acute exposure to a chemotherapeutic agent induces hyper-recombination in distantly descendant cells and in their neighbors. Oncogene. 2005 Jul 28;24(32):5016-25.

Chemical mechanisms of inflammation-induced sequence rearrangements
Kiziltepe T, Yan A, Dong M, Jonnalagadda VS, Dedon PC, Engelward BP. Delineation of the chemical pathways underlying nitric oxide-induced homologous recombination in mammalian cells. Chem Biol. 2005 Mar;12(3):357-69.

Fluorescence detection of recombination in vivo
Hendricks CA, Almeida, KH, Stitt, MS, Jonnalagadda, VS, Rugo, RE, Kerrison, GF, Engelward BP. Spontaneous mitotic homologous recombination at an enhanced yellow fluorescent protein (EYFP) cDNA direct repeat in transgenic mice. Proc. Natl. Acad. Sci. USA. 2003 May 27;100(11):6325-30.

DNA repair enzymes can promote nitric-oxide-induced recombination
Spek EJ, Vuong LN, Matsuguchi T, Marinus MG, Engelward BP. Nitric oxide-induced homologous recombination in Escherichia coli is promoted by DNA glycosylases. J. Bacteriol. 2002 Jul;184(13): 3501-7.


Selected Publications

Tay IJ, Park JJH, Price AL, Engelward BP, Floyd SR. HTS-Compatible CometChip Enables Genetic Screening for Modulators of Apoptosis and DNA Double-Strand Break Repair. SLAS Discov. 2020

Ngo LP, Owiti NA, Swartz C, Winters J, Su Y, Ge J, Xiong A, Han J, Recio L, Samson LD, Engelward BP. Sensitive CometChip assay for screening potentially carcinogenic DNA adducts by trapping DNA repair intermediates. Nucleic Acids Res. 2020 Feb 20;48(3):e13.

Wilson MR, Jiang Y, Villalta PW, Stornetta A, Boudreau PD, Carrá A, Brennan CA, Chun E, Ngo L, Samson LD, Engelward BP, Garrett WS, Balbo S, Balskus EP. The human gut bacterial genotoxin colibactin alkylates DNA. Science. 2019 Feb 15;363(6428).

Ngo LP, Chan TK, Ge J, Samson LD, and Engelward BP. Microcolony size distribution assay enables high-throughput cell survival quantitation. Cell Reports. 2019 26:1668-1678.

Kay J, Thadhani E, Samson L, Engelward B. Inflammation-induced DNA damage, mutations and cancer. DNA Repair (Amst). 2019 Nov;83:102673.

Parrish MC, Chaim IA, Nagel ZD, Tannenbaum SR, Samson LD, Engelward BP. Nitric oxide induced S-nitrosation causes base excision repair imbalance. DNA Repair. 2018 68:25-33.

Wadduwage DN, Kay J, Singh VR, Kiraly O, Sukup-Jackson MR, Rajapakse J, Engelward BP, So PTC. Automated fluorescence intensity and gradient analysis enables detection of rare fluorescent mutant cells deep within the tissue of RaDR mice. Sci Rep. 2018 Aug 14;8(1):12108

Sykora P, Witt KL, Revanna P, Smith-Roe SL, Dismukes J, Lloyd DG, Engelward BP, Sobol RW. Next generation high throughput DNA damage detection platform for genotoxic compound screening. Scientific Reports. 2018 Feb 9;8(1):2771.

Townsend TA, Parrish MC, Engelward BP, Manjanatha MG. The development and validation of EpiComet-Chip, a modified high-throughput comet assay for the assessment of DNA methylation status. Environmental and Molecular Mutagenesis. 2017 Aug;58(7):508-521.

Nagel ZD, Engelward BP, Brenner DJ, Begley TJ, Sobol RW, Bielas JH, Stambrook PJ, Wei Q, Hu JJ, Terry MB, Dilworth C, McAllister KA, Reinlib L, Worth L, Shaughnessy DT. Towards precision prevention: Technologies for identifying healthy individuals with high risk of disease. Mutation Research. 2017 Aug;800-802:14-28.

Kimoto T, Kay JE, Li N, Engelward BP. Recombinant cells in the lung increase with age via de novo recombination events and clonal expansion. Environmental and Molecular Mutagenesis. 2017 Apr;58(3):135-145.

Chan TK, Loh XY, Peh HY, Tan WNF, Tan WSD, Li N, Tay IJJ, Wong WSF, Engelward BP. House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs. The Journal of Allergy and Clinical Immunology, in press.

Rai P, Parrish M, Tay IJ, Li N, Ackerman S, He F, Kwang J, Chow VT, Engelward BP. (2015) Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells. Proc. Natl. Acad. Sci. USA. Jun 30;112(26):E3421-30.

Na L, Parrish M, Chan T, Yin L, Rai P, Yamada Y, Kiraly O, Chow VTK, Engelward BP. Influenza infection induces host DNA damage and dynamic DNA damage 1 responses during tissue regeneration. Cell and Molecular Life Sciences. 2015, Aug;72(15):2973-88.

Kiraly O, Gong G, Olipitz W, Muthupalani S, Engelward BP. Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS Genet. 2015 Feb 3;11(2):e1004901.

Ge J, Chow DN, Fessler JL, Weingeist DM, Wood DK, Engelward BP. Micropatterned comet assay enables high throughput and sensitive DNA damage quantification.Mutagenesis. 2015 Jan;30(1):11-9.

Ge J, Prasongtanakij S, Wood DK, Weingeist DM, Fessler J, Navasummrit P, Ruchirawat M, and Engelward BP. CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells. J Vis Exp. 2014 Oct 18;(92):e50607

Tan KS, Choi H, Jiang X, Yin L, Seet JE, Patzel V, Engelward BP, Chow VT. Micro-RNAs in regenerating lungs: an integrative systems biology analysis of murine influenza pneumonia. BMC Genomics, 2014 15:587.

Kiraly O, Gong G, Roytman MD, Yamada Y, Samson LD, Engelward BP. DNA glycosylase activity and cell proliferation are key factors in modulating homologous recombination in vivo. Carcinogenesis. 2014 Aug 25. pii: bgu177.

Sukup-Jackson MR, Kiraly O, Kay JE, Na L, Rowland EA, Winther KE, Chow DN, Kimoto T, Matsuguchi T, Jonnalagadda VS, Maklakova VI, Singh VR, Wadduwage DN, Rajapakse J, So PT, Collier LS, Engelward BP. Rosa26-GFP direct repeat (RaDR-GFP) mice reveal tissue- and age-dependence of homologous recombination in mammals in vivo. PLoS Genet. 2014 Jun5;10(6):e1004299.

Watson C, Ge J, Cohen J, Pyrgiotakis G, Engelward BP, Demokritou P. High-throughput screening platform for engineered nanoparticle-mediated genotoxicity using CometChip technology. ACS Nano. 2014 Mar 25;8(3):2118-33.

Ge J, Wood DK, Weingeist DM, Prasongtanakig S, Navasumrit P, Ruchirawat M, Engelward BP. Standard fluorescent imaging of live cells is highly genotoxic. Cytometry A. 2013 Jun;83(6):552-60.

Weingeist DM, Ge J, Wood DK, Mutamba JT, Huang Q, Rowland EA, Yaffe MB, Floyd S, and Engelward BP. Single cell microarray enables high throughput evaluation of DNA double strand breaks and DNA repair inhibitors. Cell Cycle. 2013 Mar 15;12(6):907-15.

Li N, Yin L, Thévenin D, Yoshiyuki Y, Limmon G, Chen J, Chow VT, Engelman DM, Engelward BP. Peptide targeting and imaging of damaged lung tissue in influenza-infected mice. Future Microbiol. 2013 Feb;8(2):257-69.

Olipitz W, Wiktor-Brown D, Shuga J, Pang B, McFaline J, Lonkar P, Thomas A, Mutamba JT, Greenberger JS, Samson LD, Dedon PC, Yanch JC, Engelward BP. Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation. Environ Health Perspect. 2012 Aug;120(8):1130-6.

Yamada Y, Limmon GV, Zheng D, Li N, Li L, Yin L, Chow VT, Chen J, Engelward BP. Major shifts in the spatio-temporal distribution of lung antioxidant enzymes during influenza pneumonia. PLoS One. 2012;7(2):e31494.

Mutamba JT, Svilar D, Prasongtanakii S, Wang XH, Lin YC, Dedon PC, Sobol RW, Engelward BP. XRCC1 and base excision repair balance in response to nitric oxide. DNA Repair (Amst). 2011 Dec 10;10(12):1282-93.

Wiktor-Brown DM, Sukup-Jackson MR, Fakhraldeen SA, Hendricks CA, Engelward BP. p53 null fluorescent yellow direct repeat (FYDR) mice have normal levels of homologous recombination. DNA Repair (Amst). 2011 Dec 10;10(12):1294-9.

Rugo RE, Mutamba JT, Mohan KN, Yee T, Chaillet JR, Greenberger JS, and Engelward BP. Methyltransferases mediate cell memory of a genotoxic insult. Oncogene. 2011 Feb 10;30(6):751-756.

Wood DK, Weingeist DM, Bhatia SN, Engelward BP. Single cell trapping and DNA damage analysis using microwell arrays. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10008-13.

Olipitz W, Hembrador S, Davidson M, Yanch JC, Engelward BP. Development and characterization of a novel variable low dose-rate irradiator for in vivo mouse studies. Health Phys. 2010 May;98(5):727-34.

Wiktor-Brown DM, Kwon HS, Nam YS, So PT, Engelward BP. Integrated one- and two-photon imaging platform reveals clonal expansion as a major driver of mutation load. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10314-9.

Wiktor-Brown DM, Olipitz W, Hendricks CA, Rugo RE, Engelward BP. Tissue-specific differences in the accumulation of sequence rearrangements with age. DNA Repair (Amst). 2008 May 3;7(5):694-703.

Helleday T, Lo J, van Gent DC, Engelward BP. DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Repair (Amst). 2007 Jul 1;6(7):923-35.

Wiktor-Brown DM, Hendricks CA, Olipitz W, Engelward BP. Age-dependent accumulation of recombinant cells in the mouse pancreas revealed by in situ fluorescence imaging. Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11862-7.

Nowosielska A, Smith SA, Engelward BP, Marinus MG. Homologous recombination prevents methylation-induced toxicity in Escherichia coli. Nucleic Acids Res. 2006 May 2;34(8):2258-68.

Rugo RE, Almeida KH, Hendricks CA, Jonnalagadda VS, Engelward BP. A single acute exposure to a chemotherapeutic agent induces hyper-recombination in distantly descendant cells and in their neighbors. Oncogene. 2005 Jul 28;24(32):5016-25.

Jonnalagadda VS, Matsuguchi T, Engelward BP. Interstrand crosslink-induced homologous recombination carries an increased risk of deletions and insertions. DNA Repair (Amst). 2005 May 2;4(5):594-605.

Kiziltepe T, Yan A, Dong M, Jonnalagadda VS, Dedon PC, Engelward BP. Delineation of the chemical pathways underlying nitric oxide-induced homologous recombination in mammalian cells. Chem Biol. 2005 Mar;12(3):357-69.