Dr. Hong Zan's lab is interested in the molecular mechanisms involved in immunoglobulin SHM and CSR, as well as plasma cell differentiations in antibody responses to microbial pathogens and tumoral cells. We also like to understand how dysregulation of these B cell differentiation processes lead to the production of pathogenic autoantibodies in autoimmune diseases, such as systemic lupus and rheumatoid arthritis, and how aberrant CSR and SHM machineries lead to lymphomagenesis.
Their current research is focused on the roles of the
epigenetic marks, including DNA modifications, histone acetylation and
microRNA, transcription factors and DNA repair proteins in these B cell
specific processes, and the regulation of these elements by genetic,
hormonal and environmental factors.
They also aim to establish
mechanistic paradigms for inhibition of CSR, SHM and plasma cell
differentiation, and, therefore, blunting of class-switched and
hypermutated antibodies and autoantibodies, and atopic IgEs that mediate
allergy and anaphylaxis through epigenetic modulators, including
histone deacetylase inhibitors that regulate histone modification and
Zan, H. and P. Casali. 2014. MicroRNA in Lupus. Autoimmunity. In press. (“Epigenetics and lupus” monographic issue, Guest Editor Hong Zan)
Zan, H. and P. Casali. 2014. Immunoglobulin somatic hypermutation and class switch DNA recombination. In: Encyclopedia of Medical Immunology. I.R. Mackay & N.L. Rose, Eds. Springer-Verlag GmbH, Heidelberg, in press.
Li, G., H. Zan, Z. Xu, and P. Casali. 2013. Epigenetics in the antibody response. Trend. Immunol. 34:460-470
Li, G., E.J. Pone, T. Mai, T.S. Lam, D. Tran, H. Zan, Z. Xu and P. Casali. 2013. Combinatorial histone modifications target class-switch DNA recombination to S regions. Cell Reports. 5:702-714
Zan, H. and P. Casali. 2013. Regulation of Aicda expression and AID activity. Autoimmunity, 46:83-101.
Pone, E.J., J. Zhang, T. Mai, C.A. White, G. Li, P. Patel, A. Al-Qahtani, J. Sakakura, H. Zan, Z. Xu and P. Casali. 2012. BCR-signalling synergizes with TLR-signalling for induction of AID and immunoglobulin class switch DNA recombination through the non-canonical NF-kB pathway. Nature Commun. 3:767 (1-12).
Xu, Z., H. Zan, E.J. Pone, T. Mai and P. Casali. 2012. Immunoglobulin class switch DNA recombination: induction, targeting and beyond. Nature Rev. Immunol., 12:517-531
Zan, H., C.A. White, L. Thomas, J. Zhang, G. Li, E.S. Yu, Z. Xu, T. Mai and P. Casali. 2012. Rev1 recruits Ung to switch regions and enhances dU glycosylation for immunoglobulin class switch DNA recombination. Cell Reports, 2:1220-1232.
Zan, H., J. Zhang, A. Al-Qahtani, E.J. Pone, C.A. White, D. Lee, L. Yel, T. Mai and P. Casali. 2011. Endonuclease G plays a role in immunoglobulin class switch DNA recombination by introducing double-strand breaks in switch regions. Mol. Immunol. 48:610-622.
White, C.A., J.S. Hawkins, E.J. Pone, E.S. Yu, T. Mai, A. Al-Qahtani, H. Zan and P. Casali. 2011. AID dysregulation on in lupus-prone MRL/Faslpr/lpr mice increases class switch DNA recombination and promotes interchromosomal c-Myc/IgH loci translocations: modulation by HoxC4. Autoimmunity, 44:585-598.
Xu, Z., Z. Fulop, G. Wu, E.J. Pone, J. Zhang, T. Mai, L.M. Thomas, A. Al-Qahtani, C.A. White, S.-R.Park, P. Steinacker, Z. Li, J. Yates 3rd, B. Herron, M. Otto, H. Zan, H. Fu and P. Casali. 2010. 14-3-3 adaptor proteins target S region-specific 5'-AGCT-3' motifs and recruit AID to unfold class switch DNA recombination. Nature Struct. Mol. Biol. 17:1124-1135.
Mai, T.*, H. Zan*, J. Zhang, J.S. Hawkins, Z. Xu and P. Casali. 2010. Estrogen receptors bind to and activate the promoter of the HoxC4 gene to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, Immunoglobulin class-switch DNA recombination and somatic hypermutation. J. Biol. Chem. 285:37797-37810. (* These authors contributed equally to this work)
Zan, H., J. Zhang, S. Ardeshna, Z. Xu, S.R. Park and P. Casali. 2009. Lupus-prone MRL/faslpr/lpr mice display increased AID expression and extensive DNA lesions, comprising deletions and insertions, in the immunoglobulin locus: concurrent upregulation of somatic hypermutation and class switch DNA recombination. Autoimmunity. 42:89-103.
Park S.-R.*, H. Zan*, Z. Pal, J. Zhang, A. Al-Qhatani, E.J. Pone, Z. Xu, T. Mai and P. Casali. 2009. HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation. Nature Immunol. 10:540-550 (*These authors contributed equally to this work)
Zan, H. and P. Casali. 2008. AID- and Ung-dependent generation of resected double-strand DNA breaks in immunoglobulin class switch DNA recombination: a postcleavage role for AID. Mol. Immunol. 46:45-61.
Wu, X., C.Y. Tsai, M. Patam, H. Zan, S.M. Lipkin and P. Casali. 2006. A role for the MutL mismatch repair Mlh3 protein in immunoglobulin class switch DNA recombination and somatic hypermutation. J. Immunol.176:5426-5437.
Casali, P., S. Pal, Z. Xu and H. Zan. 2006. DNA repair in antibody somatic hypermutation. Trends Immunol. 27:313-321.
Zan, H., N. Shima, Z. Xu, A. Al-Qahtani, A.J. Evinger, III, Y. Zhong, J.C. Schimenti and P. Casali. 2005. The translesion DNA polymerase q plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J. 24:3757-3769.
Casali, P. and H. Zan. 2004. Class switching and Myc translocation: how does DNA break? Nature Immunol. 5:1101-1103.