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Zachary D Nagel, Ph.D.

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Research Interests

Why can some people tolerate exposure to DNA damaging agents such as radiation, sunlight, reactive oxygen species and tobacco smoke, while others develop disease? Why do some cancers respond to radiation and chemotherapy, while others do not? Research in the Nagel lab is focused on finding answers to these questions by studying DNA repair. We are using novel multiplex, cell-based DNA repair assays (FM-HCR) together with biochemical and biophysical approaches to understand DNA repair at the molecular, cellular and population levels, with the long-term goal of advancing personalized prevention and treatment of disease.

One area of research is focused on defining the structural and mechanistic biology of the molecular machines that repair DNA damage. This project is aimed at understanding how mutations affect the function of DNA repair complexes, and identifying cancer-specific therapeutic targets.

A second major initiative is to measure DNA repair capacity in cancer cells and generate mathematical models that predict whether cancer cells will be sensitive to killing with specific DNA damaging agents. The goal of this project is to identify personalized cancer therapy strategies.

A third major interest involves measuring inter-individual differences in DNA repair capacity in non-cancerous cells. The goal of this work is to identify functional biomarkers that can be used for individualized predictions regarding disease risk and sensitivity to exposure to radiation and other DNA damaging agents.

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. U01ES029520 (NAGEL, ZACHARY DAVID) Sep 15, 2018 - Jun 30, 2023
    NIH
    Multi-Pathway DNA Repair Capacity Measurements in Lung Cancer Patients and Healthy Controls
    Role: Principal Investigator

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. Toprani SM, Bitounis D, Huang Q, Oliveira N, Ng KW, Tay CY, Nagel ZD, Demokritou P. High-Throughput Screening Platform for Nanoparticle-Mediated Alterations of DNA Repair Capacity. ACS Nano. 2021 03 23; 15(3):4728-4746. PMID: 33710878.
    Citations:    Fields:    
  2. Nguyen MT, Moiani D, Ahmed Z, Arvai AS, Namjoshi S, Shin DS, Fedorov Y, Selvik EJ, Jones DE, Pink J, Yan Y, Laverty DJ, Nagel ZD, Tainer JA, Gerson SL. An effective human uracil-DNA glycosylase inhibitor targets the open pre-catalytic active site conformation. Prog Biophys Mol Biol. 2021 Mar 03. PMID: 33675849.
    Citations:    Fields:    
  3. Toprani SM, Scheibler C, Nagel ZD. Interplay Between Air Travel, Genome Integrity, and COVID-19 Risk vis-a-vis Flight Crew. Front Public Health. 2020; 8:590412. PMID: 33392133.
    Citations:    Translation:HumansPHPublic Health
  4. Alvarado-Cruz I, Mahmoud M, Khan M, Zhao S, Oeck S, Meas R, Clairmont K, Quintana V, Zhu Y, Porciuncula A, Wyatt H, Ma S, Shyr Y, Kong Y, LoRusso PM, Laverty D, Nagel ZD, Schalper KA, Krauthammer M, Sweasy JB. Differential immunomodulatory effect of PARP inhibition in BRCA1 deficient and competent tumor cells. Biochem Pharmacol. 2021 02; 184:114359. PMID: 33285109.
    Citations:    Fields:    
  5. Owiti NA, Nagel ZD, Engelward BP. Fluorescence Sheds Light on DNA Damage, DNA Repair, and Mutations. Trends Cancer. 2021 Mar; 7(3):240-248. PMID: 33203608.
    Citations:    Fields:    
  6. Ferri-Borgogno S, Barui S, McGee AM, Griffiths T, Singh PK, Piett CG, Ghosh B, Bhattacharyya S, Singhi A, Pradhan K, Verma A, Nagel Z, Maitra A, Gupta S. Paradoxical Role of AT-rich Interactive Domain 1A in Restraining Pancreatic Carcinogenesis. Cancers (Basel). 2020 Sep 21; 12(9). PMID: 32967217.
    Citations: 1     
  7. Lee KJ, Mann E, Wright G, Piett CG, Nagel ZD, Gassman NR. Exploiting DNA repair defects in triple negative breast cancer to improve cell killing. Ther Adv Med Oncol. 2020; 12:1758835920958354. PMID: 32994807.
    Citations: 2     
  8. Koyen AE, Madden MZ, Park D, Minten EV, Kapoor-Vazirani P, Werner E, Pfister NT, Haji-Seyed-Javadi R, Zhang H, Xu J, Deng N, Duong DM, Pecen TJ, Frazier Z, Nagel ZD, Lazaro JB, Mouw KW, Seyfried NT, Moreno CS, Owonikoko TK, Deng X, Yu DS. EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair. Oncogene. 2020 06; 39(25):4798-4813. PMID: 32457468.
    Citations: 3     Fields:    Translation:HumansCells
  9. O'Sullivan MJ, Mitchel JA, Das A, Koehler S, Levine H, Bi D, Nagel ZD, Park JA. Irradiation Induces Epithelial Cell Unjamming. Front Cell Dev Biol. 2020; 8:21. PMID: 32117962.
    Citations: 4     
  10. Houl JH, Ye Z, Brosey CA, Balapiti-Modarage LPF, Namjoshi S, Bacolla A, Laverty D, Walker BL, Pourfarjam Y, Warden LS, Babu Chinnam N, Moiani D, Stegeman RA, Chen MK, Hung MC, Nagel ZD, Ellenberger T, Kim IK, Jones DE, Ahmed Z, Tainer JA. Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nat Commun. 2019 12 11; 10(1):5654. PMID: 31827085.
    Citations: 13     Fields:    Translation:HumansCells
  11. Russo M, Crisafulli G, Sogari A, Reilly NM, Arena S, Lamba S, Bartolini A, Amodio V, Magrì A, Novara L, Sarotto I, Nagel ZD, Piett CG, Amatu A, Sartore-Bianchi A, Siena S, Bertotti A, Trusolino L, Corigliano M, Gherardi M, Lagomarsino MC, Di Nicolantonio F, Bardelli A. Adaptive mutability of colorectal cancers in response to targeted therapies. Science. 2019 12 20; 366(6472):1473-1480. PMID: 31699882.
    Citations: 32     Fields:    Translation:HumansCells
  12. Lee KJ, Piett CG, Andrews JF, Mann E, Nagel ZD, Gassman NR. Defective base excision repair in the response to DNA damaging agents in triple negative breast cancer. PLoS One. 2019; 14(10):e0223725. PMID: 31596905.
    Citations: 2     Fields:    Translation:HumansCells
  13. Xiao AY, Maynard MR, Piett CG, Nagel ZD, Alexander JS, Kevil CG, Berridge MV, Pattillo CB, Rosen LR, Miriyala S, Harrison L. Sodium sulfide selectively induces oxidative stress, DNA damage, and mitochondrial dysfunction and radiosensitizes glioblastoma (GBM) cells. Redox Biol. 2019 09; 26:101220. PMID: 31176262.
    Citations: 7     Fields:    Translation:HumansCells
  14. Chan EM, Shibue T, McFarland JM, Gaeta B, Ghandi M, Dumont N, Gonzalez A, McPartlan JS, Li T, Zhang Y, Bin Liu J, Lazaro JB, Gu P, Piett CG, Apffel A, Ali SO, Deasy R, Keskula P, Ng RWS, Roberts EA, Reznichenko E, Leung L, Alimova M, Schenone M, Islam M, Maruvka YE, Liu Y, Roper J, Raghavan S, Giannakis M, Tseng YY, Nagel ZD, D'Andrea A, Root DE, Boehm JS, Getz G, Chang S, Golub TR, Tsherniak A, Vazquez F, Bass AJ. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature. 2019 04; 568(7753):551-556. PMID: 30971823.
    Citations: 42     Fields:    Translation:HumansCells
  15. Nagel ZD, Beharry AA, Mazzucato P, Kitange GJ, Sarkaria JN, Kool ET, Samson LD. Fluorescent reporter assays provide direct, accurate, quantitative measurements of MGMT status in human cells. PLoS One. 2019; 14(2):e0208341. PMID: 30811507.
    Citations:    Fields:    Translation:HumansCells
  16. Moore S, Berger ND, Luijsterburg MS, Piett CG, Stanley FKT, Schräder CU, Fang S, Chan JA, Schriemer DC, Nagel ZD, van Attikum H, Goodarzi AA. The CHD6 chromatin remodeler is an oxidative DNA damage response factor. Nat Commun. 2019 01 16; 10(1):241. PMID: 30651562.
    Citations: 6     Fields:    Translation:HumansCells
  17. Shen J, Ju Z, Zhao W, Wang L, Peng Y, Ge Z, Nagel ZD, Zou J, Wang C, Kapoor P, Ma X, Ma D, Liang J, Song S, Liu J, Samson LD, Ajani JA, Li GM, Liang H, Shen X, Mills GB, Peng G. ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade. Nat Med. 2018 05; 24(5):556-562. PMID: 29736026.
    Citations: 82     Fields:    Translation:HumansAnimalsCells
  18. Parrish MC, Chaim IA, Nagel ZD, Tannenbaum SR, Samson LD, Engelward BP. Nitric oxide induced S-nitrosation causes base excision repair imbalance. DNA Repair (Amst). 2018 08; 68:25-33. PMID: 29929044.
    Citations: 5     Fields:    Translation:AnimalsCells
  19. Chaim IA, Nagel ZD, Jordan JJ, Mazzucato P, Ngo LP, Samson LD. In vivo measurements of interindividual differences in DNA glycosylases and APE1 activities. Proc Natl Acad Sci U S A. 2017 11 28; 114(48):E10379-E10388. PMID: 29122935.
    Citations: 6     Fields:    Translation:HumansCells
  20. 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. Mutat Res. 2017 08; 800-802:14-28. PMID: 28458064.
    Citations: 4     Fields:    Translation:HumansCells
  21. Nagel ZD, Kitange GJ, Gupta SK, Joughin BA, Chaim IA, Mazzucato P, Lauffenburger DA, Sarkaria JN, Samson LD. DNA Repair Capacity in Multiple Pathways Predicts Chemoresistance in Glioblastoma Multiforme. Cancer Res. 2017 01 01; 77(1):198-206. PMID: 27793847.
    Citations: 35     Fields:    Translation:HumansAnimalsCells
  22. Beharry AA, Nagel ZD, Samson LD, Kool ET. Fluorogenic Real-Time Reporters of DNA Repair by MGMT, a Clinical Predictor of Antitumor Drug Response. PLoS One. 2016; 11(4):e0152684. PMID: 27035132.
    Citations: 6     Fields:    Translation:HumansCells
  23. McFaline-Figueroa JL, Braun CJ, Stanciu M, Nagel ZD, Mazzucato P, Sangaraju D, Cerniauskas E, Barford K, Vargas A, Chen Y, Tretyakova N, Lees JA, Hemann MT, White FM, Samson LD. Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide. Cancer Res. 2015 Aug 01; 75(15):3127-38. PMID: 26025730.
    Citations: 32     Fields:    Translation:HumansAnimalsCells
  24. Nagel ZD, Chaim IA, Samson LD. Inter-individual variation in DNA repair capacity: a need for multi-pathway functional assays to promote translational DNA repair research. DNA Repair (Amst). 2014 Jul; 19:199-213. PMID: 24780560.
    Citations: 18     Fields:    Translation:HumansCells
  25. Nagel ZD, Margulies CM, Chaim IA, McRee SK, Mazzucato P, Ahmad A, Abo RP, Butty VL, Forget AL, Samson LD. Multiplexed DNA repair assays for multiple lesions and multiple doses via transcription inhibition and transcriptional mutagenesis. Proc Natl Acad Sci U S A. 2014 May 06; 111(18):E1823-32. PMID: 24757057.
    Citations: 48     Fields:    Translation:HumansCells
  26. Nagel ZD, Cun S, Klinman JP. Identification of a long-range protein network that modulates active site dynamics in extremophilic alcohol dehydrogenases. J Biol Chem. 2013 May 17; 288(20):14087-14097. PMID: 23525111.
    Citations: 23     Fields:    Translation:Cells
  27. Nagel ZD, Meadows CW, Dong M, Bahnson BJ, Klinman JP. Active site hydrophobic residues impact hydrogen tunneling differently in a thermophilic alcohol dehydrogenase at optimal versus nonoptimal temperatures. Biochemistry. 2012 May 22; 51(20):4147-56. PMID: 22568562.
    Citations: 20     Fields:    Translation:Cells
  28. Nagel ZD, Dong M, Bahnson BJ, Klinman JP. Impaired protein conformational landscapes as revealed in anomalous Arrhenius prefactors. Proc Natl Acad Sci U S A. 2011 Jun 28; 108(26):10520-5. PMID: 21670258.
    Citations: 34     Fields:    Translation:Cells
  29. Nagel ZD, Klinman JP. Update 1 of: Tunneling and dynamics in enzymatic hydride transfer. Chem Rev. 2010 Dec 08; 110(12):PR41-67. PMID: 21141912.
    Citations: 51     Fields:    
  30. Nagel ZD, Klinman JP. A 21st century revisionist's view at a turning point in enzymology. Nat Chem Biol. 2009 Aug; 5(8):543-50. PMID: 19620995.
    Citations: 111     Fields:    Translation:Cells
  31. Miqyass M, Marosvölgyi MA, Nagel Z, Yocum CF, van Gorkom HJ. S-state dependence of the calcium requirement and binding characteristics in the oxygen-evolving complex of photosystem II. Biochemistry. 2008 Jul 29; 47(30):7915-24. PMID: 18593200.
    Citations: 9     Fields:    Translation:AnimalsCells
  32. Nagel ZD, Klinman JP. Tunneling and dynamics in enzymatic hydride transfer. Chem Rev. 2006 Aug; 106(8):3095-118. PMID: 16895320.
    Citations: 92     Fields:    Translation:AnimalsCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.