Currently, the Sheng Lab is focused on three areas of research:
Mechanism of B Cell Receptor (Bcr) Maturation Following Infection and Vaccination
We use probe-sorting to identify antigen-specific BCRs and apply high-throughput BCR repertoire sequencing technology, including bulk and heavy-light paired sequencing, to trace longitudinal development of antigen-specific antibody lineages following infection (HIV-1, influenza, etc.) and vaccination. The goal is to elucidate mechanism of coevolution of pathogen/immunogen and antibody lineages, to evaluate vaccine efficacy, and to optimize vaccination strategy.
Learning How Nature Designs Antibody
Accumulation of somatic hypermutation is critical for antibody affinity maturation, but our current understanding of structural and functional roles of somatic hypermutation is very limited. We have been developing a platform to incorporate bioinformatic (BCR repertoire, molecular dynamics simulation, evolution, deep learning, etc.) and biophysical (Surface Plasmon Resonance,Small-angle X-ray scattering, etc.) approaches to elucidate structural and biophysical basis of modulation of antibody affinity by somatic hypermutation. We will then apply the obtained knowledge to optimize therapeutic antibodies.
B Cell in Autoimmune Diseases and Cancers
Auto-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. We use single cell BCR and transcriptome sequencing to characterize BCR and transcriptome features related to autoimmune diseases (IgA Nephropathy, Systemic Lupus Erythematosus, Rheumatoid Arthritis, etc.), with the goal of elucidating disease etiology. We also apply similar approaches to study functional roles of B cells in tumor micro-environment (Liver cancer, Intrahepatic Cholangiocellular Carcinoma, etc.).