In 2009, he established the Laboratory of B-cell Repertoire Analysis and ultimately attained the position of associate professor of medicine. In the HIV field, Dr. Bonsignori isolated multiple broadly neutralizing antibody B cell lineages from chronically HIV-1 infected individuals and characterized antibody/virus co-evolution to rationally select immunogen candidates for sequential vaccination schemes. Dr. Bonsignori developed a high-throughput memory B cell culture system for the functional screening of memory B cells at the single-cell level and conceptualized a novel framework for steering the immune response through immunogen design based on the probability of individual mutations and their effect on antibody effector functions. He later applied some of the technologies and workflows to study B cell responses to P. falciparum and Zika virus. Before NIAID, Dr. Bonsignori supported the Duke University student COVID-19 surveillance program by establishing a high-throughput workflow for the rapid accessioning, pooling and storage of nasal swab samples that sustained the screening of up to 20,000 samples per week.