Hundreds of studies in the last decade have established that AID/APOBEC and other DNA-damaging enzymes (e.g. RAG recombinases) can drive and exacerbate cancers. These activities are carried out through mediating genome-wide mutations or double-strand DNA breaks and chromosomal translocations that underlie tumor initiation and drive aggressiveness and treatment resistance during cancer progression. The genome destabilizing activities of these DNA/RNA-damaging enzymes is thus thought to contribute to clonal heterogeneity and evolution of tumors, leading to the current understanding that enzymes that damage DNA/RNA are tumorigenic or pro-tumor. At the same time, emerging hints in the literature point to instances where DNA/RNA-damaging enzyme expression also correlates with anti-tumor phenotypes. Manipulating the activities of these enzymes can afford therapeutic opportunities. Our work in this area includes gaining a better understanding of cellular processes that act up-or downstream from DNA/RNA-editing enzymes and testing the impact of targeted therapies in cancer biology and in immune response to cancer cells. We also work on development of targeted therapeutics.

Representative publications in this area:

  1. Borzooee F, Asgharpour M., Quinlan E., Grant M., Larijani M. Viral subversion of APOBEC3s: lessons for anti-tumor immunity and tumor immunotherapy. International Rev. Immunol. 2017. Dec 6;37(3):151-164.
  2. King JJ, Larijani M. A novel regulator of AID/APOBECs: Schrödinger's CATalytic pocket, Frontiers Imm. 2017, Apr 6;8:351.
  3. King JJ, Manuel CA, Barrett CV, Raber S, Lucas HM, Sutter P, Larijani M. Catalytic pocket inaccessibility of activation induced cytidine deaminases a safeguard against excessive mutagenic activity, Structure. 2015. Apr 7; 23(4):615-27

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