Research

Our lab is dedicated to understanding the intricate biology of germinal centers (GCs), which are specialized structures in lymphoid organs essential for refining antibody responses. These microenvironments orchestrate the process of affinity maturation, during which antibodies are fine-tuned to target pathogens with high specificity. Our research aims to investigate the cellular and molecular mechanisms that regulate these processes, with particular emphasis on three key areas:

B cell receptor (BCR) signaling in GC B cells

The positive selection of germinal center B cells relies on the affinity of BCRs to antigens, with optimal BCR signaling and balanced T cell help being crucial for effective antibody affinity maturation and diversity. The delicate balance between BCR signaling and help from follicular T helper cells (Tfh) governs expansion of selected clones in the GCs. To understand these mechanisms, we are investigating the signaling dynamics of B cell receptors (BCRs) and their interaction with co-receptors such as CD19, CD21, and CD22 in positively selected GC B cells. A major goal of this research is to examine the spatial organization of these receptors on the cell membrane and how their reorganization, mediated by glycan remodeling through Tfh cell help, facilitates positive selection.

Antibody durability and diversity

A major challenge in vaccine development is the gradual waning of immunity over time, a process that remains poorly understood. While recall responses typically enhance the durability and diversity of immune protection, some viral infections or repeated vaccinations can hinder the formation of secondary germinal centers (GCs), often due to memory from prior antigen exposures. Our lab focuses on unraveling the pathways driving memory and plasma cell differentiation within GCs and understanding the factors that determine this dichotomy. Utilizing GC-specific fate-mapping mouse models, we aim to trace the migration, maintenance, and reentry of differentiated memory B cells in GCs. Additionally, we seek to define the reentry thresholds of memory B cells during secondary responses and investigate how these cells influence overall antibody diversity.

IgG1 memory B cells (MBCs) as reservoir in allergies

Our lab is also investigating the role of IgG1 MBCs in allergic responses. Although allergic reactions are primarily driven by IgE antibodies, IgE-producing plasma and MBCs are short-lived. Instead, long-term allergic memory is maintained by IgG1 MBCs, which act as reservoirs capable of rapidly undergoing class-switch recombination to produce IgE upon allergen exposure. We aim to uncover the mechanisms that sustain IgG1 memory and facilitate the class-switching process to IgE. Additionally, we are investigating whether IgG1 memory established early in life contributes to the progression of inflammatory conditions later in life, often referred to as the "allergic march”.

By understanding the molecular underpinnings of GC biology, we aim to identify novel strategies for enhancing vaccine efficacy against pathogens. Additionally, our work seeks to provide a deeper understanding of the pathological mechanisms that drive autoimmunity and allergies, potentially offering new therapeutic targets for managing these conditions.

Publications and patents

Selected Publication

Chapter in book

Patents filed (in USA)

Opportunities

We are seeking highly motivated PhD candidates to join our research group. Our lab is also offering postdoctoral opportunities for highly motivated researchers to join our lab through national postdoctoral programs.