Massari, Paola, Ph.D.
Ph.D. and Post-doctoral training: University of Naples “Federico II”, Naples, Italy and Chiron-Biocine, Siena, Italy
The main interest of the Massari’s laboratory is in understanding how host mucosal epithelial cells/bacteria interactions influence bacterial pathogenesis and disease. A major focus is on the Gram-negative bacteria Neisseriae, which comprise both pathogenic and non-pathogenic organisms that colonize the human host. N. meningitidis is an opportunistic nasopharyngeal pathogen; some strains are invasive and can cause fatal meningococcal disease and septicemia while others persist as carrier strains; nasopharyngeal colonization by N. lactamica is hardly ever associated with disease and this organism is considered a commensal; N. gonorrhoeae infection of the human genital tract causes the sexually transmitted disease, gonorrhea. A number of bacterial factors, as well as host cell receptors at the immediate bacterial-host cell interface contribute to epithelial cell colonization, invasion and activation by Neisseriae.
Porins are major outer membrane proteins expressed by all Neisseriae, regardless of pathogenicity. However, porins have significant sequence variability among strains, specifically in regions (loops) that are surface-exposed on the bacterial membrane. The PorB porin is recognized by host cells via the Toll-like receptor 2 (TLR2) and signals via the TLR2/TLR1 and MyD88-dependent pathway. However, PorB from pathogenic meningococci bind to and signals via TLR2 with a different specificity than PorB from commensal strains, due to amino acid sequence differences in the loop regions. The mechanism(s) of differential TLR recognition and signaling by these porins is one of the areas of our research. Our studies investigate on the porin/TLR2 structural features, how these can affect epithelial cell functional pathways in vitro and their potential consequences on the outcomes of pathogenic Neisseria infection of epithelial cells of the airway and genital tracts.
Additional areas of interest of the Massari’s group are in understanding the TLR-dependent effects of bacterial porins on the immune system, including their functions as both immunogens and adjuvants. This includes not only Neisserial PorB but also FomA from Fusobacterium nucleatum (an oral pathogen) and MOMP from Chlamydia. Lastly, in studies on the role of cell activation by porins and host cell apoptosis, Dr. Massari has shown a direct interact of PorB with mitochondria, which may ultimately influence host cells survival after Neisseriae infection. Dr. Massari closely collaborates with Drs. Wetzler and Genco at BU and with other investigators at national and international institutions.