Professor Reuben Harris

Biochem,Molec Biol,Biophy MEDX
Medical School
Twin Cities
Project Title: 
Role of DNA Cytidine Deaminases in Cancer

These researchers have recently shown that the DNA cytosine deaminase APOBEC3B is a probable source of somatic C-to-T mutations in breast cancer. APOBEC3B messenger RNA is upregulated in most primary breast tumors and breast cancer cell lines and endogenous APOBEC3B protein is predominantly nuclear and the only detectable source of DNA C-to-U editing activity in breast cancer cell-line extracts. This research was published in Nature in 2013.

Extending their initial analyses, the researchers recently addressed whether APOBEC3B is broadly responsible for mutagenesis in multiple tumor types. They analyzed gene expression data and mutation patterns, distributions and loads for 19 different cancer types, with over 4,800 exomes and 1,000,000 somatic mutations using public TCGA data. They showed that APOBEC3B is upregulated, and its preferred target sequence is frequently mutated and clustered in at least six distinct cancers: bladder, cervix, lung (adenocarcinoma and squamous cell carcinoma), head and neck, and breast. This work was published in Nature Genetics in 2013 and in JNCI Cancer Spectrum in 2018. Research showing that A3 enzymes can be synthetically lethal in cell systems lacking uracil repair was published in PNAS in 2019. The group has also shown that certain haplotypes of APOBEC3H may also play a role in breast, lung, and other cancers; this research was published in Nature Communications in 2016. Mouse models of APOBEC3A showed that APOBEC can cause tumors with significant apobec mutation signature; this research was published in the Journal of Experimental Medicine in 2020. 

More human and mouse model data whole genome analysis is ongoing.

Project Investigators

William Brown
Dr. Michael Carpenter
Cameron Durfee
Professor Reuben Harris
Rena Levin-Klein
Postdoctoral Fellow Jennifer McCann
Seyed Arad Moghadasi
Sofia Moraes
Amanda Rieffer
Artur Serebrenik
Nadine Shaban
Bojana Stefanovska
Travis Stratton
Dr. Nuri Temiz
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