Larijani Lab

We are interested in genome-mutating processes.

We study processes that mutate and alter the genetic codes of DNA/RNA. DNA/RNA-mutating processes have diverse biological functions ranging from modulating innate and adaptive immune responses, the evolution of host and viral genomes, and epigenetic changes underlying developmental reprogramming and tissue differentiation. On the other hand, these same beneficial DNA/RNA-altering processes can cause mutations and/or chromosomal breaks leading to the transformation of healthy cells into cancer. Furthe rmore, these processes can be erroneously activated in cells of non-immune tissues. Mutational processes often continue operating in tumors resulting in increased aggressiveness, escape from recognition by the immune system as well as resistance to treatment.

The overarching theme of our research is to understand the molecular/cellular mechanisms and biological impacts of DNA/RNA-mutating processes in health and disease.

We are interested in every dimension of DNA/RNA-mutating processes, including their molecular structures, biochemical mechanisms, cellular regulation, impact on health and disease, and also theirevolution and divergent functions throughout speciation.
Our methodologies are interdisciplinary and integrate biochemistry, structural biology, molecular & cellular biology, evolutionary biology, whole organism approaches, and computational biology.

Thematically, we work on two broad fronts: first, understanding how DNA/RNA-mutating processes impact human health and diseases and mapping out their therapeutic potential in diseases like cancer; second, discovering how they evolved, presently function, or used to function throughout speciation as well as discovering novel DNA/RNA-editing enzymes. Our broad areas of research include:

1) Elucidating the dynamic structures of genome mutating enzymes
2) Understanding the biochemical mechanisms and structure: function relationships of DNA/RNA-mutating enzymes
2) Mapping the regulation of the activity of DNA/RNA-mutating enzymes in healthy cells
3) Discovering how DNA/RNA-mutating enzymes function in the genesis and progression of cancer
4) Investigating the ways DNA/RNA-editing enzymes influence the immune response to cancer and to viruses
5) Discovery of ancient DNA/RNA-mutating enzymes and mapping the evolution and co-evolutionary scenarios involving DNA/RNA mutating processes throughout life on earth

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Lab Page:

Lab Room:

SSB 6159

Lab Phone: 

(778) 782-6817

Selected Publications

  • King JJ, Borzooee, F, Im J, Asgharpour M, Ghorbani A, Diamond CP, Fifield H, Berghuis L, Larijani M.  Structure-based design of first-generation small molecule inhibitors targeting the catalytic pockets of AID, APOBEC3A and APOBEC3B. ACS Pharmacology & Translational Science. 2021.  ACS Pharmacol Transl Sci. 2021 Jul 19;4(4):1390-1407 (selected for cover figure)
  • Ghorbani A, Quinlan EM, Larijani M. Evolutionary comparative analyses of DNA-editing enzymes of the immune system: from 5-dimensional description of protein structures to immunological insights and applications to protein engineering. Frontiers in Immunology. 2021. May 31;12:642343.
  • King JJ, Larijani M. Structural plasticity of substrate selection by activation-induced cytidine deaminase as a regulator of its genome-wide mutagenic activity. FEBS Letters. 2020. 595(1):3-13 (selected for cover figure)
  • Branton SA, Ghorbani A, Bolt BN, Fifield H, Berghuis LM, Larijani M.  Activation-induced cytidine deaminase can target multiple topologies of double-stranded DNA in a transcription-independent manner. FASEB J. 2020. Jul;34(7):9245-9268
  • Holland SJ, Berghuis LM, King JJ, Iyer L, Sikora K, Fifield H, Peter S, Quinlan EM, Fumiaki S, Prashant S, Trancoso I, Iwanami N, Temereva E, Strohmeier C, Kuratani S, Venkatesh B, Evanno G, Aravind L, Schorpp M, Larijani M*, Boehm T*. Expansions, diversification and inter-individual copy number variation of AID/APOBEC family cytidine deaminase genes in lampreys. Proc Natl Acad Sci2018. Mar 19. pii: 201720871 (*ML and TB co-senior authors)
  • 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 6:1-14. doi: 10.1080/08830185
  • Quinlan EM, King JJ, Amemiya CT, Hsu E, Larijani M. Biochemical regulatory features of AID have remained conserved from lamprey to humans. Mol Cell. Biol. 2017. Jul 17. pii: MCB.00077-17
  • King JJ, Larijani M. A novel regulator of AID/APOBECs: Schrödinger's CATalytic pocket, Frontiers Imm. 2017, Apr 6;8:351
  • 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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