Richard Malley

Richard Malley's laboratory studies the acquired and innate immune responses to common human pathogens, including Streptococcus pneumoniae, Staphylococcus aureus, Mycobacterium tuberculosis and Salmonella typhi and paratyphi. A major area of interest of the laboratory is the development of alternatives to the expensive and serotype-dependent pneumococcal vaccines. Starting with the mucosal application of killed whole unencapsulated pneumococci, Malley and colleagues identified a novel mechanism of immunity to pneumococcal colonization that may have important implications for the generation of immunity to this and other mucosal pathogen: the generation of specific IL-17A-producing CD4+ T cells that greatly reduce the duration and density of mucosal colonization. The natural extension of this work has been efforts to identify antigens from pneumococcus, staphylococcus and mycobacteria that elicit protective T cell responses. The Malley laboratory is also working to further define this mechanism of protection. With funding from PATH, the Malley laboratory is pursuing the development of killed, whole cell vaccines for use in developing countries. This vaccine is currently undergoing Phase II clinical trials in Kenyan children, to evaluate immune responses and protection against pneumococcal carriage. The Malley laboratory is actively involved in the discovery and testing of vaccines against a number of pathogens, including pneumococcus, S. aureus, Mycobacterium tuberculosis, and Salmonellae, using a combination of genomic and proteomic analysis, immunological techniques, novel vaccine platforms (including a recently discovered Multiple Antigen Presenting System, or MAPS) and animals models. Another area of interest concerns the study of the regulatory mechanisms that underlie the bistable expression of the type 1 pneumococcal pilus, a virulence factor that has been associated with increased capacity to colonize the host. Work in the laboratory has uncovered a complex network of regulatory mechanisms between the pilus genes and other regulatory genes in pneumococcus. Finally, the Malley laboratory is interested in studying the transcriptome of both pneumococcus and S. aureus using materials both from animal models as well as clinical samples obtained from colonized or infected children.