Director, Rochester General Hospital Research InstituteView Michael Pichichero's Full Profile
Our Laboratory is focused on the goal of intervening in the disease process of nasopharyngeal colonization by respiratory bacterial pathogens Streptococcus pneumoniae, Nontypeable Haemophilus influenzae and Moraxella catarrhalis.
Clearly the pathogens must colonize the NP and become the dominant organism. To be dominant they must out - compete other normal flora and other potential bacterial pathogens. So can we intervene in the pathogenesis of a respiratory bacterial pathogen gaining dominance and an increased inoculum? Are the potential pathogens working together as co-pathogens? If the normal flora maintains dominance then AOM, sinusitis, pneumonia and bronchitis would be prevented.
Nearly always an AOM, sinusitis, pneumonia or bronchitis is preceded by a viral URI. We know the viral URI promotes up-regulation of NP epithelial cell receptors, down-regulates innate and adaptive immune responses, increases viscosity of nasal mucus and damages NP cells thereby exposing additional receptors for respiratory pathogens to utilize. Can we intervene in this pathogenic process?
When enough antibody is available on the NP mucosa (by transudation from serum) that is directed to appropriate target antigens that are surface-exposed on a respiratory pathogen, then attachment of the pathogen can be prevented. We need to know how much antibody is needed and to which specific antigens for each of our target respiratory pathogens.
What is the role of cellular immunity? Th1, Th2, Th17, T reg, T memory, B memory. Is there a subgroup of individuals where cellular immunity is more important?
The innate response, particularly in the NP, may vary among human hosts. Cytokines, chemokines, complement, neutrophils are released and mobilized in response to colonization and infection. Success of the innate response may predict the need for an adaptive response to clear colonization and infection.
Do biofilms form in the NP or middle ear or bronchi? If so, does this occur in a subpopulation or all individuals who become colonized or infected with the respiratory bacterial pathogens under study? If so, how can we intervene in biofilm formation?
Human and mouse Immunology: PCR, qPCR, RT-PCR, FACS, CyTOF, Elispot, ELISA, Functional assays (bactericidal, anti-adherence), cell culture
Gene cloning, protein purification and characterization for vaccine development
Bacterial genetics: Whole genome sequencing, virulence determinants, pathogenesis
Mouse Models: Sepsis, pneumonia, otitis media, nasopharyngeal colonization, protection, correlates of protection,
Infectious disease pathogenesis and immune mechanistic investigations
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