ATM phosphorylates the FATC domain of DNA-PK cs at threonine 4102 to promote non-homologous end joining.
Lu H, Zhang Q, Laverty DJ, Puncheon AC, Williams GJ, Nagel ZD, Chen BP, Davis AJ.
bioRxiv. 2023 Feb 02. PMID: 36778257
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.
Lu H, Zhang Q, Laverty DJ, Puncheon AC, Williams GJ, Nagel ZD, Chen BP, Davis AJ.
bioRxiv. 2023 Feb 02. PMID: 36778257
Scheibler C, Toprani SM, Mordukhovich I, Schaefer M, Staffa S, Nagel ZD, McNeely E.
Front Public Health. 2022. 10:947068. PMID: 36483259
Blee AM, Li B, Pecen T, Meiler J, Nagel ZD, Capra JA, Chazin WJ.
Cancer Res. 2022 08 03. 82(15):2704-2715. PMID: 35687855
Cheong A, Nagel ZD.
Front Immunol. 2022. 13:899574. PMID: 35935942
Meas R, Nititham J, Taylor KE, Maher S, Clairmont K, Carufe KEW, Kashgarian M, Nottoli T, Cheong A, Nagel ZD, Gaffney PM, Criswell LA, Sweasy JB.
ACR Open Rheumatol. 2022 Sep. 4(9):760-770. PMID: 35708944
Koster S, Gurumurthy RK, Kumar N, Prakash PG, Dhanraj J, Bayer S, Berger H, Kurian SM, Drabkina M, Mollenkopf HJ, Goosmann C, Brinkmann V, Nagel Z, Mangler M, Meyer TF, Chumduri C.
Nat Commun. 2022 02 24. 13(1):1030. PMID: 35210413
Bitounis D, Huang Q, Toprani SM, Setyawati MI, Oliveira N, Wu Z, Tay CY, Ng KW, Nagel ZD, Demokritou P.
NanoImpact. 2022 01. 25:100379. PMID: 35559885
Piett CG, Pecen TJ, Laverty DJ, Nagel ZD.
Nat Protoc. 2021 09. 16(9):4265-4298. PMID: 34363069
Ngo LP, Kaushal S, Chaim IA, Mazzucato P, Ricciardi C, Samson LD, Nagel ZD, Engelward BP.
Free Radic Biol Med. 2021 10. 174:89-99. PMID: 34324980
Toprani SM, Bitounis D, Huang Q, Oliveira N, Ng KW, Tay CY, Nagel ZD, Demokritou P.
ACS Nano. 2021 03 23. 15(3):4728-4746. PMID: 33710878
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