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Assessing genome sequence integrity in normal human cells

Description: PROJECT NARRATIVE Human somatic cells are exposed to DNA damaging agents on a daily basis from both endogenous and exogenous sources, resulting in a broad range of DNA lesions. DNA repair of this damage is a complex process, and errors result in DNA mutations. DNA mutations cause cancer and have also been implicated in age-related diseases as well as aging itself. Here we propose to integrate, further optimize and validate two recently developed DNA mutation assays into the first next-generation sequencing-based, comprehensive assay for testing human genome sequence integrity. The assay will then be tested to measuring the mutagenic effects of tobacco smoke in lung, buccal, and blood cells. The assay developed in the proposed project would potentially allow, for the first time, the testing of global genome sequence integrity to assess individual risk of lung cancer in relation to exposure to tobacco smoke, as reflected in non-invasive specimens amenable to epidemiologic studies.
Funding type: cooperative_agreement
Funder scheme: U01
Start date: 2018-08-15
End date: 2023-05-31
Investigator: SIMON D SPIVACK
Institution: ALBERT EINSTEIN COLLEGE OF MEDICINE
Funded outputs count: 30
Funder award ID: U01ES029519
OpenAlex ID: G5700867877
2026 · Elizabeth Pan, Alexander Maslov, et al. · Experimental & Molecular Medicine
2025 · Arturo Bujarrabal-Dueso, George A. Garinis, et al. · Nature Reviews Drug Discovery · 29
2024 · Johanna Heid, Ronald Cutler, et al. · BMC Research Notes · 2
2024 · Lei Zhang, Moonsook Lee, et al. · bioRxiv (Cold Spring Harbor Laboratory) · 1
2024 · Peijun Ren, Jie Zhang, et al. · GeroScience · 29
2023 · Lei Zhang, Moonsook Lee, et al. · Nature Protocols · 26
2023 · Alexander Y Maslov, Jan Vijg · Current Opinion in Genetics & Development · 9
2023 · Shixiang Sun, Daisy Sproviero, et al. · bioRxiv (Cold Spring Harbor Laboratory) · 2
2023 · Jan Vijg, Björn Schumacher, et al. · Trends in Molecular Medicine · 27
2022 · Peijun Ren, Xiao Dong, et al. · Frontiers in Aging · 51
2022 · Jan Vijg, Steven N. Austad · Cold Spring Harbor Perspectives in Medicine · 9
2022 · Alexander Y. Maslov, Sergey Makhortov, et al. · Science Advances · 58
2022 · Shixiang Sun, Kristina Brazhnik, et al. · Journal of Clinical Investigation · 16
2021 · Lei Zhang, Xiao Dong, et al. · Science Advances · 52
2021 · Shixiang Sun, Yujue Wang, et al. · Nucleic Acids Research · 47
2021 · Björn Schumacher, Joris Pothof, et al. · Nature · 911
2021 · Jan Vijg · Ageing Research Reviews · 121
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