ZiZhang Sheng, PhD

The Sheng lab uses interdisciplinary approaches to elucidate the mechanisms of humoral immune response to infection and vaccine and to understand the role of autoantibodies in autoimmunity.

Currently, the Sheng lab focuses on three areas of research:

Immune response to infection and vaccination.

We sequence antigen-specific antibody repertoire and develop antibodomics methods to study immune responses of humans and animal models. The goals are to identify signatures and epitopes of antibody responses to infectious diseases and vaccines, elucidate the mechanisms of antibody affinity maturation and neutralization, and determine immune features associated with protection. The knowledge we obtained from these studies will guide vaccine design and protection efficacy evaluation. The pathogens we currently study include HIV-1, malaria, SARS-CoV-2, and influenza.

Learning how nature designs antibody.

Accumulation of somatic hypermutation is critical for antibody affinity maturation, but our current understanding on structural and functional roles of somatic hypermutation is still limited. We have been developing a platform to incorporate bioinformatics (BCR repertoire, molecular dynamics simulation, molecular evolution, etc.) and biochemical approaches to elucidate structural basis of modulation of antibody affinity by somatic hypermutation. The findings will be used to develop knowledge-based methods to engineer therapeutic antibodies. We also develop a bioinformatics pipeline for optimization of antibodies with therapeutic potential.

B cells in autoimmune diseases and cancers

Self-reactive B cells appear in many autoimmune diseases and play an important role in disease progression. But how auto-reactive B cells escape immune surveillance and develop is still poorly characterized. To address this question, we apply single cell BCR sequencing technology to characterize genetic features of auto-reactive BCRs and to investigate their longitudinal development trajectories. We also perform single cell transcriptome sequencing to identify disease associated B cell populations and cellular factors. Currently, we are studying Systemic Lupus Erythematosus and IgA Nephropathy. We also apply similar approaches to study functional roles of B cells in liver tumor micro-environment.