• Primary Faculty Profiles
• Adjunct Faculty Profiles
• Crane, John, M.D., Ph.D., Assistant Professor
• Genco, Robert, Ph.D., Distinguished Professor
• Gill, Steven, Ph.D.
• Knight, Paul, M.D. and Ph.D., Professor
• Lesse, Alan, Ph.D., Professor
• Murphy, Timothy, Ph.D., Professor
• O'Brian, Mark, Ph.D., Professor
• Rittenhouse-Olson, Kate, Ph.D., Associate Professor
• Russo, Thomas, Ph.D., Assistant Professor
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Education:

1979-1981, Fellowship, Tufts University, Boston, MA
1976-1979, Residencey, Cornell University, New York, NY
1976, M.D., Tufts University, Boston, MA
1972, Bachelor of Science, New York University, New York,NY

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Research Interests:

Work in my laboratory focuses in three broad, related areas:

• Pathogenesis of infection by Haemophilus influenzae and Moraxella catarrhalis
• Bacterial infection in chronic obstructive pulmonary disease
• Vaccine development for H. influenzae and M. catarrhalis

The approach is to apply basic laboratory methods to study the pathogenesis of respiratory tract bacterial pathogens.  Applying genomic analysis of isolates has resulted in the discovery that strains of H. influenzae that cause infection in adults with chronic obstructive pulmonary disease (COPD) have combinations of genes that are important for virulence specifically in this setting.  Work is underway to investigate the mechanisms by which virulence factors encoded by these genes cause infection.  This work is supported by an NIH (RO1) grant.

An ongoing 14 year prospective study of adults with COPD has characterized the role of bacterial infection in COPD.  This study has generated thousands of clinical isolates, serum samples and sputum samples, all associated with detailed clinical data. This study has formed the foundation of studies of H. influenzae, M. catarrhalis, Streptococcus pneumoniae and Pseudomonas aeruginosa which are important pathogens in COPD. Molecular typing of isolates, analysis of molecular epidemiology, characterization of immune responses, elucidation of bacterial antigens as mediators of inflammation and a variety of other studies are underway.  This work is supported by a Merit Review grant from the Department of Veterans Affairs.

M. catarrhalis is now established as an important cause of otitis media (middle ear infections) in children and lower respiratory tract infections in adults with COPD.  A vaccine to prevent these infections would have an enormous impact.  Work is underway to use a genome mining approach to identify novel vaccine antigens for M. catarrhalis.  Several promising vaccine antigens are in various stages of development and additional new vaccine antigens are being identified.  This work is supported by an NIH (RO1) grant.

Relevant references:

1. Fernaays MM, Lesse AJ, Sethi S, Cai X, Murphy TF.  Differential genome content of nontypeable Haemophilus influenzae from adults with chronic obstructive pulmonary disease.  Infection and Immunity 74:3366-74 2006.

2. Murphy TF, Kirkham C, Lesse AJ.  Construction of a mutant and characterization of the role of the vaccine antigen P6 in the outer membrane integrity of nontypeable Haemophilus influenzae. Infection and Immunity 74:5169-76, 2006.

3. Fernaays MM, Lesse AJ, Cai X, Murphy TF. Characterization of igaB, a novel IgA protease gene in nontypeable Haemophilus influenzae.  Infection and Immunity 74:5860-5870, 2006.

4. Murphy TF, Brauer AL, Sethi S, Kilian M, Cai X, Lesse AJ.  Haemophilus haemolyticus: a human respiratory tract commensal to be distinguished from Haemophilus influenzae.  Journal of Infectious Diseases 195:81-89, 2007.

5. Sethi S, Sethi R, Eschberger K, Lobbins P, Cai X, Grant BJ, Murphy TF.  Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 176:356-61, 2007.

6. Sethi S, Wrona C, Eschberger K, Lobbins P, Cai X, Murphy TF.  Inflammatory profile of new bacterial strain exacerbations of chronic obstructive pulmonary disease.  American Journal of Respiratory and Critical Care Medicine 177:491-7, 2008.

7. Murphy TF, Brauer AL, Eschberger K, Lobbins P, Grove L, Cai X, Sethi S.  Pseudomonas aeruginosa in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 177(8):853-60, 2008.

8. Ruckdeschel EA, Kirkham C, Lesse AJ, Hu Z, Murphy TF.  Mining the Moraxella catarrhalis genome: identification of potential vaccine antigens expressed during human infection.  Infection and Immunity 76:1599-607, 2008.