cancer genetics, B cell malignancies, chromosomal translocations, DNA damage, DNA repair
2002 Graduated cum laude - University of Pittsburgh, B.S., Microbiology
2006 Graduate Education Travel Award - City of Hope
2008 Rachmiel Levine Student Communication Award - City of Hope
2006-2008 American Heart Association Pre-Doctoral Fellowship
2010-2015 ARCS Foundation, Los Angeles Founder Chapter, John H. Richardson Postdoctoral Fellowship
2017 Department of Pathology Paper of the Year - University of Southern California
2018 FASEB Travel Award
2019 Department of Pathology Talk of the Year - University of Southern California
Chromosomal translocations are a recurrent, transformative feature of many human lymphoid neoplasms and occur following formation of DNA double-strand breaks (DSBs). While critical to the etiology of B cell lymphomas, the origin of these DSBs remains unknown. Using genetic and pharmacological approaches, the Pannunzio lab seeks to understand how internal factors (torsional stress, transcription, replication, DNA modifying enzymes) and external factors (reactive oxygen species, radiation, chemotherapy drugs, environmental toxins) contribute to DSB formation. Using the latest technology, we quantify DSBs in human B cells carrying mutations in disease relevant genes or exposed to DNA damaging agents. We also genetically engineer the S. cerevisiae model system to carry human break-prone regions to screen for new factors related to DSB formation in human cells. Our preliminary data has led us to focus on topoisomerases, enzymes that resolve topological tension in DNA. Our data suggests that topoisomerase loss causes DNA to adopt abnormal, non-B form structures that are exposed to damage. We propose that a combination of genetic background and exposure to compounds that affect topoisomerase activity may underlie the formation of translocations that are a precursor to many B cell malignancies.
Pedulla ML, Ford ME, Houtz JM, Karthikeyan T, Wadsworth C, Lewis JA, Jacobs-Sera D, Falbo J, Gross J, Pannunzio NR, Brucker W, Kumar V, Kandasamy J, Keenan L, Bardarov S, Kriakov J, Lawrence JG, Jacobs WR Jr, Hendrix RW, Hatfull GF. (2003) Origins of Highly Mosaic Mycobacteriophage Genomes. Cell, 113(2): 171-82. (cover article)
Ghosh P, Pannunzio NR, Hatfull GF. (2005). Synapsis of phage Bxb1 integration: selection mechanism for the correct pair of recombination sites. J. Mol. Biol. 349(2): 331-48.
Pannunzio NR, Manthey GM, Bailis AM. (2008). Rad59 is required for the efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae. DNA repair (Amst), 7(5): 788-800.
Pannunzio NR, Manthey GM, Bailis AM. (2010). RAD59 and RAD1 cooperate in translocation formation by single-strand annealing in Saccharomyces cerevisiae. Curr Genet, 56(1): 87-100.
Liddell L, Manthey G, Pannunzio N, Bailis A. (2011). Quantitation and analysis of the formation of HO-endonuclease stimulated chromosomal translocations by single-strand annealing in Saccharomyces cerevisiae. J Vis Exp, 55: 3150.
Pannunzio NR, Manthey GM, Liddell LC, Fu BXH, Roberts CM, Bailis AM. (2012). Rad59 regulates association of Rad52 with DNA double-strand breaks. MicrobiologyOpen. Sep;1(3);285-97.
Pannunzio NR. Li S, Watanabe G, Lieber MR. (2014). Non-homologous end joining often uses microhomology: implications for alternative end joining. DNA Repair (Amst). May;17:74-80.
Zhang ZZ, Pannunzio NR, Han L, Hsieh CL, Yu K, Lieber MR. (2014). The strength of an Ig switch region is determined by its ability to drive R look formation and its number of WGCW sites. Cell Rep. Jul 24;8(2):557-69.
Zhang ZZ, Pannunzio NR, Hsieh CL, Yu K, Lieber MR. (2014). The role of G-density in switch region repeats for immunoglobulin class switch recombination. Nucleic Acids Res. Dec 1;42(21):13186-93.
Zhang ZZ, Pannunzio NR, Hsieh CL, Yu K, Lieber MR. (2015). Complexities due to single-stranded RNA during antibody detection of genomic RNA:DNA hybrids. BMC Res Notes. Apr 8,8:127.
Zhang ZZ, Pannunzio NR, Lu Z, Hsu E, Yu K, Lieber MR. (2015). The repetitive portion of the Xenopus IgH mu switch region mediates orientation-dependent class switch recombination. Molecular Immunology. Oct; 67(2PtB):524-31.
Lu Z, Pannunzio NR, Greisman H, Cesaro D, Parekh C, Lieber MR. (2015). Convergent BCL6 and lncRNA promoters demarcate the major breakpoint region for BCL6 translocations. Blood. Oct 1; 126(14):1730-1
Pannunzio NR, Lieber MR. (2016). Dissecting the roles of divergent and convergent transcription in chromosome instability. Cell Reports. Feb 9; 14(5):1025-31.
Pannunzio NR, Lieber MR. (2016). RNA polymerase collision versus DNA structural distortion: twists and turns can cause break failure. Molecular Cell. May 5; 62(3):327-34.
Chang HHY, Pannunzio NR, Adachi N, Lieber MR. (2017) Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol. May 17. (cover article)
Pannunzio NR, Lieber MR. (2017) AID and reactive oxygen species can induce DNA breaks within human chromosomal translocation fragile zones. Molecular Cell. December 7; 68:901-912. (cover article)
Pannunzio NR, Watanabe G, Lieber MR. (2018) Nonhomologous DNA end-joining for repair of DNA double-strand breaks. J Biol Chem 293:10512-10523. (cover article)
Pannunzio NR, Lieber MR. (2018) Concept of DNA Lesion Longevity and Chromosomal Translocations. Trends Biochem Sci 43:490-498. (cover article)
Pannunzio NR, Lieber MR. (2019) Constitutively Active Artemis Nuclease Recognizes Structures Containing Single-Stranded DNA Configurations. DNA Repair.
Cellular and Molecular Biosciences
Chao Family Comprehensive Cancer Center
Center for Epigenetics and Metabolism
Institute for Immunology