Reuben S. Harris, Ph.D. Assistant Professor Department of Biochemistry, Molecular Biology and Biophysics University of Alberta, Edmonton, 1997, Ph.D. rsh@umn.edu 612-624-0457 office 612-624-0459 lab

Research Interests:

Adaptive and innate mechanisms of purposeful mutation

Mutations are generally regarded as harmful, as they can lead to cancer. However, mutations can also be beneficial, as evidenced by the fact that our cellular mutation-making machinery can be harnessed and used to defend us from infection by disease-causing viruses such as HIV (which causes AIDS) and microbes. The Harris laboratory is using a number of model systems to dissect the mechanisms of two purposeful mutation programs --- antibody gene diversification and retroelement restriction. Both programs are catalyzed by potent DNA cytosine deaminases. This research will lead to a better understanding of how beneficial mutations occur, to therapeutic approaches that exploit specific aspects of these mechanisms and to knowledge of how inaccuracies in these processes contribute to cancer.

Harris Lab

Selected Recent Publications:

• Petersen-Mahrt, S.K., R.S. Harris & M.S. Neuberger (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification.  Nature, 418, 99-103.
• Harris, R.S., S.K. Petersen-Mahrt & M.S. Neuberger (2002) RNA editing protein APOBEC1 and some of its homologues can act as DNA mutators.  Molecular Cell, 10, 1247-1253.
• Harris, R.S., K.N. Bishop, A.M. Sheehy, H.M. Craig, S.K. Petersen-Mahrt, I.N. Watt, M.S. Neuberger & M.H. Malim (2003) DNA deamination mediates innate immunity to retroviral infection.  Cell, 113, 803-809.
• Liddament, M.T., W.L. Brown, A.J. Schumacher & R.S. Harris (2004) APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Current Biology, 14, 1385-1391.
• Harris, R.S. & M.T. Liddament (2004) Retroviral restriction by APOBEC proteins. Nature Reviews Immunology, 4, 868-877.
• Haché, G, M.T. Liddament & R.S. Harris (2005) The retroviral hypermutation specificity of APOBEC3F and APOBEC3G is governed by the C-terminal DNA cytosine deaminase domain. Journal of Biological Chemistry, 280, 10920-10924.
• Schumacher, A.J., D.V. Nissley & R.S. Harris (2005) APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast. Proceedings of the National Academy of Sciences USA, 102, 9854-9859.
• MacDuff, D.A., M.S. Neuberger & R.S. Harris (2006) MDM2 can interact with the C-terminus of AID but it is inessential for antibody diversification in DT40 B cells. Molecular Immunology, 43, 1099-1108.

Last modified on: March 15, 2006