Research Topics

In contrast to T cells, B cells undergo a relatively permissive selection process during development. Consequently, approximately 20% of mature naive B cells exhibit mild autoreactivity. This phenomenon is widely believed to be an evolutionary strategy designed to maximize the breadth of the immune repertoire, thereby ensuring effective defense against pathogens that employ molecular mimicry. However, the precise mechanisms by which these potentially hazardous clones maintain tolerance toward self-antigens while mounting selective immune responses against pathogens remain largely underexplored.

Our laboratory aims to identify the hidden mechanisms and molecular mediators that regulate this delicate balance between activation and tolerance. We specifically focus on the quantitative and qualitative regulation of B cell activation through the investigation of mechanotransduction, cytoskeletal regulation, differential signaling of IgM and IgD, antigen valency, and cytokine stimulation. Furthermore, we examine the impact of environmental factors, such as physiological stress, on humoral immunity. By elucidating these underlying mechanisms and "molecular switches," our research seeks to pioneer novel therapeutic approaches, ranging from "vaccine adjuvants" that maximize immune activation to "autoimmune therapies" that enhance immune tolerance.

Affinity maturation within germinal centers is critical for the production of high-quality antibodies. Central to this process is the effective "selection" of GC B cells that express high affinity B cell receptors (BCRs), generated via somatic hypermutation, and their subsequent "differentiation" into antibody secreting plasma cells. To support this highly stringent selection process, GC B cells undergo extensive intrinsic reprogramming and preparatory phases during their differentiation. However, the functional implications of these specific intrinsic changes remain largely underexplored.

Consequently, we study how germinal center B cells undergo these intrinsic preparatory changes to favor the selection of clones with superior antigen affinity. This work seeks to uncover additional intrinsic mechanisms that guide optimal clonal selection during the germinal center reaction.

The immune system programs the longevity of antibody secreting plasma cells in a highly context dependent manner. This regulation is essential not only because prolonged persistence of certain antibodies can be deleterious to the host, but also due to the spatial constraints within the survival niches that house these cells. Previous research has established that specific vaccination strategies or repeated antigenic exposures can induce exceptionally long lived plasma cells. However, the specific molecular mediators and mechanisms that determine this lifespan remain largely elusive.

Unraveling these regulatory mechanisms is a critical challenge in vaccinology, as it holds the key to overcoming current platform limitations and achieving lifelong immunity with minimal revaccination. To this end, our laboratory focuses on identifying early predictive biomarkers of vaccine efficacy within plasma cells. We are actively investigating the functional roles of these biomarkers and elucidating the upstream immune signaling pathways that govern their expression during the immune response.

The immunogenicity of a defined antigen is not static; rather, it can be profoundly modulated, both quantitatively and qualitatively, by its structural assembly, the specific adjuvants employed, the choice of delivery system, and the route of administration. Consequently, the strategic engineering of these induction parameters is essential for maximizing vaccine efficacy and tailoring the immune response to specific targets.

To address this, our team is developing integrated vaccine platforms designed to assess and achieve optimal vaccine efficacy, alongside robust analytical assays to accurately quantify these outcomes. Through interdisciplinary collaborations with diverse platform laboratories, we aim to engineer these advanced systems and apply them translationally. Our ultimate goal is to elicit precise, desirable immune profiles that overcome the limitations of conventional vaccination strategies.