My initial studies involved quantifying the direct interaction of all seven 14-3-3 adaptors (seven homologous isoforms, 14-3-3β, 14-3-3ε, 14-3-3γ, 14-3-3η, 14-3-3σ, 14-3-3τ and 14-3-3ζ) with class switch DNA recombination (CSR) factors, including activation-induced cytidine deaminase (AID, encoded by the Aicda gene), both the catalytic and regulatory subunits of protein kinase A (PKA-Cα and PKA-RIα) and uracil DNA glycosylase (Ung). I found that disrupting the interaction between 14-3-3 and AID with the naturally occurring HIV-1 viral protein R (Vpr) and Vpr peptides, an accessory protein of human immunodeficiency virus type-1 (HIV-1), inhibited CSR by disrupting 14-3-3 and AID recruitment to immunoglobulin heavy chain (IgH) switch (S) region, suggesting that naturally occurring proteins or small molecules serve as potential therapeutics to inhibit unwanted CSR.
With a strong B cell biology, molecular CSR, and cellular biology background, I have set my focus on translational research by investigating role of an autophagic protein in regulating AID expression and antibody class switching.
Lam, T., L. M. Thomas, E. J. Pone, T. Mai, C. A. White, G. Li, Z. Xu and P. Casali. 2013. Scaffold functions of 14-3-3 adaptors in B cell immunoglobulin class switch DNA recombination. PLOS ONE, 8(11): e80414. doi:10.1371/journal.pone.0080414.
Li, G., C.A. White, T. Lam, E.J. Pone, D. C. Tran, K.L. Hayama, H. Zan, Z. Xu and P. Casali. 2013. Combinatorial H3K9acS10ph histone modifications in IgH locus S regions target 14-3-3 adaptors and AID to specify antibody class-switch class DNA recombination. Cell Rep., 5(3): 702-714.
Mai T., E.J. Pone, G. Li, T. Lam, J. Moehlman, Z. Xu, and P. Casali. 2013. Induction of activation-induced cytidine deaminase – targeting adaptor 14-3-3g is mediated by NF-kB–dependent recruitment of CFP1 to the 5’-CpG-3’-rich 14-3-3g promoter and is sustained by E2A. J. Immunol. 191(4): 1895-1906.
Honors and Awards
1. American Association of Immunologists Trainee Abstract Award, American Association of Immunologists, March 2014, Travel award for the 2014 AAI Meeting in Pittsburgh, Pennsylvania.
2. NIH NIAID Immunology Research Training Grant T32 AI 60573, National Institute of Allergy and Infectious Diseases, 2013, One year training grant to support my research focused on the maturation of the antibody and autoantibody responses.
3. Science, Mathematics, And Research for Transformation Scholarship, 2011
4. Science, Mathematics, And Research for Transformation Scholarship, 2010
5. Young Artist Scholarship, Laguna College of Art and Design, Laguna Beach, CA, 2004