P. Patrick Cleary
The molecular basis for streptococci disease
Streptococci are masters of immune avoidance. S. pyogenes, the most common cause of sore throat, are also responsible for serious diseases such as rheumatic fever, heart disease, and flesh eating wound infections. My research investigates the molecular and cellular processes that lead to these infections. Current experiments aim to define the impact of surface proteins, C5a peptidase and M protein, on persistence of S. pyogenes in the host. These multifunctional proteins interact with extracellular matrix proteins and cellular receptors to target streptococci to immune tissues. Experiments attempt to define host cell signaling pathways that lead to intracellular invasion and whether infection of secondary lymphoid tissue alters the immune response to streptococci. Studies of the cellular immune response to infection are another focus, which could help understand why children fail to develop a protective immune response following infection. A collaboration with a major pharmaceutical company will soon test a C5a peptidase vaccine in humans for prevention Strep throat. Molecular genetic, immunochemical and sophisticated imaging methods are used in these studies
- Cleary, P. P. 2006. Streptococcus moves inward. Nat Med 12:384-6.
- Wang, B., S. Li, P. J. Southern, and P. P. Cleary. 2006. Streptococcal modulation of cellular invasion via TGF-beta1 signaling. Proc Natl Acad Sci U S A 103:2380-5.
- Brown, C. K., Z. Y. Gu, Y. V. Matsuka, S. S. Purushothaman, L. A. Winter, P. P. Cleary, S. B.Olmsted, D. H. Ohlendorf, and C. A. Earhart. 2005. Structure of the streptococcal cell wall C5a peptidase. Proc Natl Acad Sci U S A 102:18391-6.
- Park, H. S. and P. P. Cleary. 2005. Active and passive intranasal immunizations with streptococcal surface protein C5a peptidase prevent infection of murine nasal mucosa-associated lymphoid tissue, a functional homologue of human tonsils. Infect Immun 73:7878-86.
- Park, H. S., M. Costalonga, R. L. Reinhardt, P. E. Dombek, M. K. Jenkins, and P. P. Cleary. 2004. Primary induction of CD4 T cell responses in nasal associated lymphoid tissue during group A streptococcal infection. Eur J Immunol 34:2843-53.