MICaB Graduate Program
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Reuben S. Harris, Ph.D.
Department of Biochemistry, Molecular Biology and Biophysics
University of Alberta, Edmonton, 1997, Ph.D.
Mechanisms of Mutation in Immunity and Cancer Biology
Human cells have the capacity to produce up to nine active DNA cytosine deaminases. The seven-member APOBEC3 subfamily provides an innate immune barrier to a wide variety of DNA based parasites including transposons and viruses such as HIV-1. One family member, AID, also has an essential role in adaptive immunity by promoting antibody diversification through isotype switch recombination and somatic hypermutation. The founding family member, APOBEC1, has a role in mRNA editing, but is also likely to have innate immune functions. Despite these beneficial activities, a subset of these enzymes also poses a threat to nuclear DNA. Recent studies have revealed a major role for DNA cytosine deamination in mutagenesis in breast, head/neck, cervical, bladder, lung, and other cancer types.
The Harris lab uses a large repertoire of model systems and experimental approaches to understand both the physiological and the pathological functions of these DNA mutating enzymes. We are also interested in translating fundamental discoveries into novel therapeutics.
Selected Recent Publications:
- Harris, R.S. (2013) Cancer mutation signatures, DNA damage mechanisms, and potential clinical implications. Genome Medicine 5:87.
- Burns, M.B., N.A. Temiz & R.S. Harris (2013) Evidence for APOBEC3B mutagenesis in multiple human cancers. Nature Genetics 45:977-83.
- Burns*, M.B., L. Lackey*, M.A. Carpenter, A. Rathore, A.M. Land, B. Leonard, E.W. Refsland, D. Kotandeniya, N. Tretyakova, J.B. Nikas, D. Yee, N.A. Temiz, D.E. Donohue, R.M. McDougle, W.L. Brown, E.K. Law & R.S. Harris (2013) APOBEC3B is an enzymatic source of mutation in breast cancer. Nature 494:366–370 (*equal contributions).
- Refsland, E.W. & R.S. Harris (2013) The APOBEC3 family of retroelement restriction factors. Current Topics in Microbiology and Immunology 371:1-27.
- Carpenter, M.A., M. Li, A. Rathore, L. Lackey, E.K. Law, A.M. Land, B. Leonard, S.M.D. Shandilya, M.F. Bohn, C.A. Schiffer, W.L. Brown & R.S. Harris (2012) Methylcytosine and normal cytosine deamination by the foreign DNA restriction enzyme APOBEC3A. Journal of Biological Chemistry 287:34801-8.
- Refsland, E.W., J.F. Hultquist & R.S. Harris (2012) Endogenous origins of HIV-1 G-to-A hypermutation and restriction in the nonpermissive T cell line CEM2n. PLoS Pathogens, 8(7): e1002800
- Jäger*, S., D.Y. Kim*, J.F. Hultquist*, K. Shindo, R.S. LaRue, E. Kwon, M. Li, B.D. Anderson, L. Yen, D. Stanley, C. Mahon, J. Kane, K. Franks-Skiba, P. Cimermancic, A. Burlingame, A. Sali, C. Craik, R.S. Harris#, J.D. Gross# & N.J. Krogan# (2012) Vif hijacks CBF beta to degrade APOBEC3G and promote HIV-1 infection. Nature 481:371-5 (* equal contributions; # correspondence).