Research | Publications | Curriculum vitae (Pdf format) | Biosketch (Pdf format)
| Lab Page
Hong Zan, Ph.D.
Tel: (210) 567-3956Fax: (210) 567-6612
B lymphocytes respond to infection or immunization by diversifying the antibodies (immunoglobulin, Ig) they produce through two processes: antibody class switch DNA recombination and somatic hypermutation (SHM) of their antigen-binding regions. CSR causes a change in antibody class expression from IgM to IgG, IgA or IgE, resulting in an increased ability of the antibody to remove the pathogen. SHM, in conjunction with B cell selection, results in increases in the antigen binding ability of the antibody. Class-switched/hypermutated B cells then differentiate into plasma cells that secrete large amounts of antibodies. Both SHM and CSR are highly regulated and are effected by a two-step process: (i) DNA lesions initiated by activation-induced cytidine deaminase (AID), and (ii) lesion repair by the combined intervention of DNA replication and repair factors that include translesion DNA synthesis (TLS) polymerases. Aberrant SHM and CSR, whether due to dysregulation or off-targeting of the SHM and CSR machinery, results in diseases ranging from primary immunodeficiency, systemic or organ-specific autoimmunity, atopic IgE reactions to neoplastic transformation. In addition, epigenetic marks can “interact” with genetic programs to regulate CSR, SHM and plasma cell differentiation, thereby informing the antibody response. Epigenetic dysregulation can also result in aberrant antibody responses to exogenous antigens, such as those on viruses and bacteria, or self-antigens, such as chromatin, histones and dsDNA.
We are 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. Our 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. We 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 microRNA expression.