USC.edu

Phuong Pham

Assistant Professor (Research) of Biological Sciences
Phuong Pham
Email ppham@usc.edu Office RRI 113 Office Phone (213) 740-5191

Education

  • Ph.D. Genetics, St. Petersburg State University, 5/1993
  • M.S. Biology, St. Peterburg State University, 6/1989
    • Visiting Fellow, National Institute of Environmental Health Sciences, 04/22/1999 – 04/22/2004

  • Summary Statement of Research Interests

    My research has been devoted to addressing broad questions focused on how genomic mutations are generated in bacteria and humans. In the early years, I studied Escherichia coli DNA polymerases (Pol III, IV and V). These Pols are responsible for base substitution and frameshift mutations during replication on undamaged normal and damaged DNA templates. Subsequently, my interest has broadened to include DNA mutating enzymes, activation-induced deoxycytidine deaminase (AID) along with other members of the APOBEC protein family of DNA dependent deoxycytidine deaminases. These enzymes play an essential role in adaptive and innate immunity.
    During the past few years, a major portion of my research has shifted to studies of chromosomal dynamics of single-stranded (ss)DNA and genomic landscapes of ssDNA-protein interactions in bacteria. We have successfully designed and implemented a new ChIP-seq protocol that we call “ssGap-seq”, which combines a conventional ChIP-seq with non-denaturing sodium bisulfite treatment. This new method allows detection and mapping ssDNA-protein interactions in genomes of bacterial and higher organisms. Using “ssGap-seq”, we have mapped ssDNA interactions with two extremely important proteins in E. coli, RecA and SSB (single-strand binding protein) proteins. Our new genomic ssDNA detection techniques can be used to study chromosomal dynamics in other bacteria and eukaryotes (yeast and human). These methods should provide access to information not previously available and enable the characterization of DNA metabolic events involving ssDNA intermediates. With respect to ssDNA-protein interactions, the newly developed methods are generally applicable to investigate a wide range of DNA binding proteins beyond RecA/Rad51 and SSB/RPA, which include pretty much all proteins involved in 3R (Replication, Repair, Recombination) pathways.

  • Journal Article

    • Jaszczur, M. M., Pham, P., Ojha, D., Pham, C. Q., McDonald, J. P., Woodgate, R., Goodman, M. F. (2024). Pathogen-encoded Rum DNA polymerase drives rapid bacterial drug resistance. Nucleic Acids Res. Vol. 52 (21), pp. 12987-13002.
    • Pham, P., Wood, E. A., Dunbar, E. L., Cox, M. M., Goodman, M. F. (2024). Controlling Genome Topology with Sequences that Trigger Post-replication Gap Formation During Replisome Passage: The E. coli RRS Elements. Nucleic Acids Research. Vol. 52 (11)
    • Pham, P., Wood, E. A., Cox, M. M., Goodman, M. F. (2023). RecA and SSB genome-wide distribution in ssDNA gaps and ends in Escherichia coli. Nucleic Acids Res. Vol. 51 (112023/04/19), pp. 5527-5546.
    • Jeong, S. L., Zhang, H., Yamaki, S., Yang, C., McKemy, D. D., Lieber, M. R., Pham, P., Goodman, M. F. (2022). Immunoglobulin somatic hypermutation in a defined biochemical system recapitulates affinity maturation and permits antibody optimization. Nucleic Acids Res. Vol. 50 (202022/11/03), pp. 11738-11754.
    • Pham, P. T., Shao, Y., Cox, M. M., Goodman, M. F. (2022). Genomic Landscape of Single-stranded DNA Gapped Intermediates in Escherichia coli. Nucleic Acids Res. Vol. 50, pp. 937-951.
    • Liu, D., Goodman, M. F., Pham, P., Yu, K., Hsieh, C., Lieber, M. R. (2022). The mRNA Tether Model for Activation-Induced Deaminase and a Theory for Unifying Ig Somatic Hypermutation and Ig Class Switch Recombination. DNA Repair. Vol. 110, pp. 103271.
    • Henrikus, S. S., Henry, C., McGrath, A., Jergic, S., McDonald, J. P., Bruckbauer, S. T., Ritger, M., Cherry, M. E., Wood, E. A., Pham, P. T., Goodman, M. F., Woodgate, R., Cox, M. M., van Oijen, A. M., Ghodke, H., Robinson, A. (2020). Single-molecule live-cell imaging reveals RecB-Dependent Function of DNA Polymerase IV in Double Strand Break Repair. Nucleic Acids Res. Vol. 48, pp. 8490-8508.
    • Pham, P. T., Malik, S., Mak, C., Calabrese, P. C., Roeder, R. G., Goodman, M. F. (2019). AID-RNA polymerase II transcription-dependent deamination of IgV DNA. Nucleic Acids Res. (2019/10/01)
    • Mak, C. H., Pham, P. T., Goodman, M. F. (2019). Random Walk Enzymes: Information Theory, Quantum Isomorphism, and Entropy Dispersion. J Phys Chem A. Vol. 123 (132019/03/09), pp. 3030-3037.
    • Pham, P. T., Afif, S. A., Shimoda, M., Maeda, K., Sakaguchi, N., Pedersen, L. C., Goodman, M. F. (2017). Activation-induced deoxycytidine deaminase: Structural basis for favoring WRC hot motif specificities unique among APOBEC family members. DNA Repair (Amst). Vol. 54, pp. 8-12.
    • Eid, M. M., Shimoda, M., Singh, S. K., Almofty, S. A., Pham, P. T., Goodman, M. F., Maeda, K., Sakaguchi, N. (2017). Integrity of immunoglobulin variable regions is supported by GANP during AID-induced somatic hypermutation in germinal center B cells. Int Immunol. Vol. 29 (5), pp. 211-220.
    • Pham, P. T., Afif, S. A., Shimoda, M., Maeda, K., Sakaguchi, N., Pedersen, L. C., Goodman, M. F. (2016). Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification. DNA Repair (Amst). Vol. 43, pp. 48-56.
    • Senavirathne, G., Bertram, J. G., Jaszczur, M., Chaurasiya, K. R., Pham, P. T., Mak, C. H., Goodman, M. F., Rueda, D. (2015). Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution. Nat Commun. Vol. 6, pp. 10209.
    • Mak, C. H., Pham, P., Afif, S. A., Goodman, M. F. (2015). Random-walk enzymes. Phys. Review E. Vol. 92, pp. 032717.
    • Wei, L., Chahwan, R., Wang, S., Wang, X., Pham, P. T., Goodman, M. F., Bergman, A., Scharff, M. D., MacCarthy, T. (2015). Overlapping hotspots in CDRs are critical sites for V region diversification. Proc Natl Acad Sci U S A. Vol. 112 (72015/02/04), pp. E728-37.
    • Maeda, K., Almofty, S. A., Singh, S. K., Eid, M. M., Shimoda, M., Ikeda, T., Koito, A., Pham, P., Goodman, M. F., Sakaguchi, N. (2013). GANP interacts with APOBEC3G and facilitates its encapsidation into the virions to reduce HIV-1 infectivity. J. Immunol.. Vol. 191 (12), pp. 6030-6039.
    • Pham, P., Landolph, A., Mendez, C., Li, N., Goodman, M. F. (2013). A Biochemical Analysis Linking APOBEC3A to Disparate HIV-1 Restriction and Skin Cancer. J Biol Chem. Vol. 288 (412013/08/28), pp. 29294-304.
    • Mak, C. H., Pham, P., Afif, S. A., Goodman, M. F. (2013). A Mathematical Model for Scanning and Catalysis on Single-stranded DNA, Illustrated with Activation-induced Deoxycytidine Deaminase. J Biol Chem. Vol. 288 (412013/08/28), pp. 29786-95.
    • Jaszczur, M., Bertram, J. G., Pham, P., Scharff, M. D., Goodman, M. F. (2013). AID and Apobec3G haphazard deamination and mutational diversity. Cell Mol Life Sci. Vol. 70 (172012/11/28), pp. 3089-108.
    • Singh, S. K., Maeda, K., Eid, M. M., Almofty, S. A., Ono, M., Pham, P., Goodman, M. F., Sakaguchi, N. (2013). GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy. Nat Commun. Vol. 4 (2013/05/09), pp. 1830.
    • Mu, Y., Prochnow, C., Pham, P., Chen, X. S., Goodman, M. F. (2012). A structural basis for the biochemical behavior of activation-induced deoxycytidine deaminase class-switch recombination-defective hyper-IgM-2 mutants. J Biol Chem. Vol. 287 (332012/06/21), pp. 28007-16.
    • Pham, P., Calabrese, P., Park, S., Goodman, M. F. (2011). Analysis of a single-stranded DNA-scanning process in which activation-induced deoxycytidine deaminase (AID) deaminates C to U haphazardly and inefficiently to ensure mutational diversity. J Biol Chem. Vol. 286 (282011/05/17), pp. 24931-42.
    • Maeda, K., Singh, S. K., Eda, K., Kitabatake, M., Pham, P., Goodman, M. F., Sakaguchi, N. (2010). GANP-mediated Recruitment of Activation-induced Cytidine Deaminase to Cell Nuclei and to Immunoglobulin Variable Region DNA. Journal of Biological Chemistry. Vol. 285 (31), pp. 23945-23953. PubMed Web Address
    • Chelico, L., Pham, P., Petruska, J., Goodman, M. F. (2009). Biochemical basis of immunological and retroviral responses to DNA-targeted cytosine deamination by activation-induced cytidine deaminase and APOBEC3G. Journal of Biological Chemistry. Vol. 284 (41), pp. 27761-27765.
    • Madia, F., Wei, M., Yuan, V., Hu, J., Gattazzo, C., Pham, P., Goodman, M. F., Longo, V. D. (2009). Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Polzeta-dependent mechanism. J Cell Biol. Vol. 186 (4), pp. 509-523. PubMed Web Address
    • Chelico, L., Pham, P., Goodman, M. F. (2009). Mechanisms of APOBEC3G-catalyzed processive deamination of deoxycytidine on single-stranded DNA. Nature Structural & Molecular Biology. Vol. 16 (5), pp. 454-455. PubMed Web Address
    • MacCarthy, T., Kalis, S. L., Roa, S., Pham, P., Goodman, M. F., Scharff, M. D., Bergman, A. (2009). V-region mutation in vitro, in vivo and in silico reveal the importance of the enzymatic properties of AID and the sequence environment. Proc Natl Acad Sci U S A. Vol. 106 (21), pp. 8629-8634.
    • Chelico, L., Pham, P., Goodman, M. F. (2009). Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. Philosophical Transactions of the Royal Society B: Biological Sciences. Vol. 364 (1517), pp. 583-593.
    • Pham, P., Zhang, K., Goodman, M. F. (2008). Hypermutation at A/T sites during G.U mismatch repair in vitro by human B-cell lysates. Journal of Biological Chemistry. Vol. 283 (46), pp. 31754-31762.
    • Pham, P., Smolka, M., Calabrese, P., Landolph, A., Zhang, K., Zhou, H., Goodman, M. F. (2008). Impact of phosphorylation and phosphorylation-null mutants on the activity and deamination specificity of activation-induced cytidine deaminase. Journal of Biological Chemistry. Vol. 283 (25), pp. 17428-17439.
    • Gawel, D., Pham, P., Fijalkowska, I. J., Jonczyk, P., Schaaper, R. M. (2008). Role of Accessory DNA Polymerases in the Escherichia coli dnaX36 Mutator Mutant. Journal of Bacteriology. Vol. 190 (5), pp. 1730-1742.
    • Pham, P., Chelico, L., Goodman, M. F. (2007). DNA deaminases AID and APOBEC3G act processively on single-stranded DNA. DNA Repair (Amst). Vol. 6 (6), pp. 689-92.
    • Bransteitter, R. R., J, S. L., Allen, S., Pham, P. T., Goodman, M. F. (2006). First AID (activation-induced cytidine deaminase) is needed to produce high affinity isotype-switched antibodies. Journal of Biological Chemistry. Vol. 281, pp. 16833-16836.
    • Chelico, L., Pham, P. T., Calabrese, P., Goodman, M. F. (2006). APOBEC3G DNA deaminase acts processively 3′ –> 5′ on single-stranded DNA. Nature Structural & Molecular Biology/Nature Publishing Group. Vol. 13, pp. 392-399.
    • Pham, P. T., Zhao, W., Schaaper, R. M. (2006). Mutator mutants of Escherichia coli carrying a defect in the DNA polymerase III tau subunit. Molecular Microbiology/Blackwell Publishing. Vol. 59, pp. 1149-1161.
    • Schlacher, K., Pham, P. T., Cox, M., Goodman, M. F. (2006). Roles of DNA polymerase V and RecA protein in SOS damage-induced mutation. Chemical Reviews/American Chemical Society Press. Vol. 106, pp. 406-419.
    • Michell, D. L., Pham, P. T., Goodman, M. F., Nancy, M. (2005). AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation. Oncogen/Nature Publishing Group. Vol. 24, pp. 5791-5798.
    • Pham, P. T., Bransteitter, R. R., Goodman, M. F. (2005). Reward versus Risk: DNA Cytidine Deaminases Triggering Immunity and Disease. Biochemistry/American Chemical Society. Vol. 44, pp. 2703-2715.
    • Bransteitter, R. R., Pham, P. T., Calabrese, P., Goodman, M. F. (2004). Biochemical analysis of hypermutational targeting by wild type and mutant activation-induced cytidine deaminase. Journal of Biological Chemistry. Vol. 279, pp. 51612-51621.
    • Tippin, B., Pham, P. T., Goodman, M. F. (2004). Error-prone replication for better or worse. Trends in Microbiology/Elsevier. Vol. 12, pp. 288-295.
    • Tippin, B., Pham, P. T., Bransteitter, R. R., Goodman, M. F. (2004). Somatic hypermutation: a mutational panacea. Advances in Protein Chemistry/Elsevier. Vol. 69, pp. 307-335.
    • Bransteitter, R., Pham, P., Scharff, M. D., Goodman, M. F. (2003). Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A. Vol. 100 (7), pp. 4102-4107.
    • Pham, P., Bransteitter, R., Petruska, J., Goodman, M. F. (2003). Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature. Vol. 424 (6944), pp. 103-107.
    • Kobayashi, S., Valentine, M. R., Pham, P., O’Donnell, M., Goodman, M. F. (2002). Fidelity of Escherichia coli DNA polymerase IV. Preferential generation of small deletion mutations by dNTP-stabilized misalignment. J Biol Chem. Vol. 277 (37), pp. 34198-34207.
    • Pham, P., Seitz, E. M., Saveliev, S., Shen, X., Woodgate, R., Cox, M. M., Goodman, M. F. (2002). Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis. Proc Natl Acad Sci U S A. Vol. 99 (17), pp. 11061-11066.
    • Pham, P., Bertram, J. G., O’Donnell, M., Woodgate, R., Goodman, M. F. (2001). A model for SOS-lesion-targeted mutations in Escherichia coli. Nature. Vol. 409 (6818), pp. 366-370.
    • Pham, P., Rangarajan, S., Woodgate, R., Goodman, M. F. (2001). Roles of DNA polymerases V and II in SOS-induced error-prone and error-free repair in Escherichia coli. Proc Natl Acad Sci U S A. Vol. 98 (15), pp. 8350-8354.
    • Silvian, L. F., Toth, E. A., Pham, P., Goodman, M. F., Ellenberger, T. (2001). Crystal structure of a DinB family error-prone DNA polymerase from Sulfolobus solfataricus. Nat Struct Biol. Vol. 8 (11), pp. 984-989.
    • Song, M. S., Pham, P. T., Olson, M., Carter, J. R., Franden, M. A., Schaaper, R. M., McHenry, C. S. (2001). The delta and delta ‘ subunits of the DNA polymerase III holoenzyme are essential for initiation complex formation and processive elongation. J Biol Chem. Vol. 276 (37), pp. 35165-35175.
    • Tang, M., Pham, P., Shen, X., Taylor, J. S., O’Donnell, M., Woodgate, R., Goodman, M. F. (2000). Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis. Nature. Vol. 404 (6781), pp. 1014-1018.
    • Pham, P. T., Olson, M. W., McHenry, C. S., Schaaper, R. M. (1999). Mismatch extension by Escherichia coli DNA polymerase III holoenzyme. J Biol Chem. Vol. 274 (6), pp. 3705-3710.
    • Pham, P. T., Olson, M. W., McHenry, C. S., Schaaper, R. M. (1998). The base substitution and frameshift fidelity of Escherichia coli DNA polymerase III holoenzyme in vitro. J Biol Chem. Vol. 273 (36), pp. 23575-23584.
USC Dornsife faculty and staff may update profiles via MyDornsife.