My laboratory focuses on two of the greatest threats to children.s health worldwide . Malaria (1 million pediatric deaths annually) and HIV/AIDS (230,000 pediatric deaths annually). The broad goals of my research program are to identify correlates of protective immunity to HIV and malaria in order to guide the rational design of vaccines and immunomodulatory therapies. We are also interested in understanding how the immune response of infants and young children differs from that of adults, in order to optimize the immunogenicity of vaccines and other strategies targeting infants.
Immunity to Childhood Malaria
We are interested in identifying in vitro correlates of protective immunity to malaria in both naturally exposed individuals and in experimental vaccination settings. There is abundant evidence that T lymphocytes are important for acquired immunity to malaria, yet the precise immune effector mechanisms responsible for protection have not been identified. Moreover, P. falciparum, which has co-evolved with humans for >100,000 years and exerted enormous selection pressure on our species, induces numerous immune regulatory mechanisms that may interfere with the generation of effective, durable malaria-specific T cell responses necessary for protection. My malaria immunology research program is based on collaborations with investigators in the Infectious Disease Division at SFGH and at Makerere University in Uganda. This work is supported by our field-based laboratory in Tororo, Uganda, a region of extremely high malaria transmission intensity.
While great strides have been made in the prevention of pediatric HIV infection in the U.S., mother-to-child transmission of HIV remains a major cause of pediatric morbidity and mortality worldwide and one HIV-infected infant is born each minute. Children infected with HIV display tremendous variability in their clinical course and rate of progression to AIDS. My laboratory seeks to identify immunologic and genetic factors underlying the high variability in the rate of progression to AIDS among children. Current studies focus on characterization of the T cell response to acute perinatal infection in infants, viral evolution following mother-to-child transmission, and the impact of HLA-associated viral mutations on the infant immune response. We are also engaged in the development of single-cell analysis assays to permit in depth characterization of antigen-specific T cells from small infant samples. These translational immunology studies are conducted in collaboration with clinical sites in the Caribbean and Africa.