Rebecca LR Powell, PhD
- ASSISTANT PROFESSOR | Medicine, Infectious Diseases
Research Topics:HIV/AIDS, Immunology, Infectious Disease
Dr. Powell received her Bachelor’s degree at the University of Toronto and her Ph. D. in Microbiology at the Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine. Her graduate work focused on HIV genetic diversity, detection and frequency of dual HIV infections, and the impact of these infections on viral recombination and the humoral immune response. Dr. Powell developed a low-cost method to rapidly detect dual HIV-1 infection and found that in normal-risk populations in West Africa, these infections were quite common, impacting genetic diversity of HIV in this area. Her analysis of a small dually-infected cohort in Cameroon led to the first study suggesting dual infections broadened the neutralizing antibody response to HIV. Dr. Powell’s early post-doctoral research at the International AIDS Vaccine Initiative (IAVI) Design and Development Lab (DDL) focused more heavily on HIV vaccine design, with emphasis on replicating, chimeric viral vectors displaying HIV-1 Envelope (Env). She developed various antibody-based assays using ultra-sensitive technologies that allowed detailed evaluation of various candidate vaccines in small and large animal studies. In her later work at the DDL, she characterized a lead Vesicular Stomatitis vector candidate in mice and assessed its immunogenicity, authoring the first study of this kind. Dr. Powell’s early research at the Icahn School of Medicine focused on HIV-1 Env V2 loop-based vaccines. She used structural models of Env to design various mutant pseudoviruses to better understand the mechanisms by which the variable loops are released from their occluded positions in the trimer and can be made available for antibody binding. She identified various mutations that can release V2, which may be highly critical V2-focused vaccine design. Dr. Powell adapted antibody-dependent cellular phagocytosis (ADCP) assays using primary neutrophils to demonstrate that V2-scaffold vaccines can focus the immune response on a single Env epitope and induce V2 Abs with Fc-dependent biologic function. Using this assay, she has analyzed the differential ADCP responses of THP-1s and neutrophils, which has determined that neutrophils exhibit a unique ADCP profile, likely due to their specialized Fc receptor repertoire. Currently, Dr. Powell is studying the contribution of ADCP by breast milk leukocytes to the relatively low rate of HIV transmission to infants breastfed by HIV-infected mothers.
MTCT of HIV
Mother-to-child transmission (MTCT) of HIV remains a crisis in many countries. ~200,000 MTCTs of HIV occur annually, with as many as half of infections being due to exposure via breastmilk (BM). Yet, only ~15% of infants breastfed by HIV-infected mothers become infected, suggesting a strong protective effect of BM itself. The contribution of milk’s cellular component has been relatively overlooked, despite evidence that maternal leukocytes are functional beyond the sites of ingestion. The only clinical HIV vaccine trial to show efficacy, RV144, correlated activities mediated by the constant (Fc) antibody (Ab) domain with protection from HIV. The essential Fc-mediated response - Ab-dependent cellular phagocytosis (ADCP) - has been understudied in the HIV context, particularly in the case of prevention of MTCT. Dr. Powell is currently conducting a comprehensive study of ADCP by BM leukocytes. This study addresses the impact of phagocytic target size/type, Ab class, and BM maturation over time on ADCP activity. These data will allow the field to better understand the potential contribution of ADCP mediated by BM cells to the reduction of MTCT of HIV, and may well be applicable to other pathogens that threaten infants over the course of lactation.