Dr. Paolo Casali's lab has a long-standing interest in studying immunoglobulins
(antibodies) and B lymphocytes in health and diseases. B cells and
high-affinity class-switched (mature) antibodies are central to host immunity
and immune memory elicited by infectious pathogens, tumoral cells and
vaccines. Dysregulation of B cell functions contributes to a range of
pathological conditions, from immunodeficiency and immunoageing to autoimmune
diseases, allergy mediated by atopic IgEs, and neoplasia.
is focusing on our fundamental understandings of how epigenetic marks drive B
cell differentiation processes, such as somatic hypermutation (SHM), class
switch DNA recombination (CSR), and B cell differentiation into plasma cells
and memory B cells. He is using a cutting-edge epigenetic modulating
approach to manipulate immunity in normal mice and autoimmunity in mouse
models, which develop disease symptoms similar to those of human systemic lupus
Zan, H., C. Tat and P. Casali. 2014. MicroRNAs in lupus. Autoimmunity
White, C.A., E.J.
Pone, T. Lam, C. Tat, K.L. Hayama, G. Li, H. Zan & P. Casali. 2014. HDAC inhibitors upregulate selected B cell microRNAs that silence AID and Blimp-1 expression for epigenetic modulation of antibody and autoantibody responses. J. Immunol., in press.
Pone, E.J., T.S. Lam,
A.L. Edinger, Z. Xu and P. Casali.
2014. B Cell Rab7 mediates induction of AID expression and class-switching in T-dependent and T-independent antibody responses. J. Immunol., in press.
Xu, Z., Z. Fulop, G.
Wu, S.-R. Park, J. Zhang, E. J. Pone, A. Al-Qahtani, T. Mai, P. Steinacker, L.
Thomas, C.A. White, Z. Li, J. R. Yates, III, B. Herron, M. Otto, H. Zan, H. Fu
and P. Casali. 2010. 14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch DNA recombination. Nature
Str. Mol. Biol. 17:1124-1135.
Mai, T., E.J. Pone,
G. Li, J. Moehlman, Z. Xu and P.
Casali. 2013. Induction of the AID-targeting adaptor 14-3-3g is mediated by NF-kB-dependent CFP1 recruitment to the 5â€™-CpG-3â€™-rich 14-3-3g promoter and sustained by E2A. J.
Li, G., H. Zan, Z. Xu
and P. Casali. 2013. Epigenetics of the antibody response. Trends
Li, G., E.J. Pone, T.
Mai, T.S. Lam, C.A. White, 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. Cell Reports
Pone, E.J., J. Zhang,
T. Mai, C.A. Clayton, 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-switching through the non-canonical NF-ÎºB 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.
Zan, H., C.A. White,
L.M. Thomas, T. Mai, G. Li, Z. Xu, J. Zhang and P. Casali. 2012. Rev1 recruits Ung to switch regions and enhances dU glycosylation for immunoglobulin class switch DNA recombination. Cell Rep.
Mai, T., H. Zan, J.
Zhang, J.S. Hawkins, Z. Xu and P. Casali.
2010. Estrogen receptors bind to and activate the HOXC4/HoxC4 promoter to potentiate HoxC4-mediated activation-induced cytosine deaminase induction, immunoglobulin class-switch DNA recombination, and somatic hypermutation. J. Biol. Chem. 285: 37797-37810.