ZiZhang Sheng, PhD

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

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

• Immune response to infection and vaccination: We develop computational methods to study immune responses of humans and animal models. In collaboration with labs at ADARC, we sequence viral antigen-specific B cell receptors (BCRs) to identify immune signatures of infections including HIV-1, SARS-CoV-2, and influenza. Our research reveals a class of IGHV1-2 derived neutralizing antibodies that are potent and prevalent in human response to SARS-CoV-2. In collaboration with the Vaccine Research Center at NIH, we study the longitudinal maturation trajectories of broadly HIV-1 neutralization antibodies (bnAbs) following sequential or/and cocktail immunizations. Our studies reveal distinct roles of different immunogens for bnAb potency and breadth development, which provide information for optimizing HIV-1 vaccine strategy.
• 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.
• 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, Myelin oligodendrocyte glycoprotein antibody disease, and IgA Nephropathy. We also apply similar approaches to study functional roles of B cells in liver tumor micro-environment.