Dr. Julie Zikherman is an Associate Professor in the Department of Medicine at UCSF and serves as Associate Chief for Basic Research in the Division of Rheumatology. Her laboratory is focused on understanding how B cell behavior is regulated after encounter with either “self” or “foreign” antigens, and how this translates into effector responses including antibody production. Her lab seeks to define the rules that govern B cell responses to specific features of antigens, including antigen affinity, valency and co-stimulatory signals. The lab further aims to understand how regulatory mechanisms that normally keep self-reactive B cells in check are disrupted to produce autoimmunity, and how they can be harnessed to restore tolerance and optimize vaccine responses. The lab takes a range of approaches that span mouse genetics, cellular immunology, biochemistry, and genomics in order to address these questions. In particular, Dr. Zikherman’s group has exploited novel reporter mice (NUR77-eGFP transgenic) in which antigen receptor signaling rapidly drives expression of green fluorescent protein (GFP) in T and B lymphocytes. This reporter serves as an in vivo sensor of both self and foreign antigen encounter, and has enabled the lab to identify naturally occurring self-reactive B cells and explore their development. This in turn led to work showing that downregulation of IgM, but not IgD, antigen receptor is a critical B cell tolerance mechanism. More recently, the lab has defined the role of the nuclear receptor NUR77 and closely related members of the NR4A family in negative regulation of B cell responses to both self and foreign antigens. This, along with future work, aims to deepen our understanding B cell biology for the purpose of developing novel therapeutic approaches to manipulate antigen-specific responses in the context of immune-mediated disease as well as vaccination.
Julie Zikherman, MD