Faculty

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Richard J. O'Callaghan, PhD

Richard O'Callaghan.jpg

Professor
(601) 984-1700
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Education
PhD, University of Mississippi Medical Center

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Primary research interest

There are two prime objectives of our research:
  • We use the eye as a model of infection to discover the virulence mechanisms of bacteria and the interaction of bacteria and host defenses; the eye is a precise and unique model that allows repeated observations of the ongoing infectious process.
  • We seek findings that will help in the prevention and/or treatment of eye infections, especially in terms of arresting tissue damage.

Our studies of experimental bacterial keratitis in the rabbit have shown that once bacteria reach a million colony forming units per cornea, the pathogenic processes initiated by bacterial products cannot be reversed by the administration of fortified antibiotics alone or in combination with antiinflammatory drugs. Bacterial toxins and/or enzymes released into the cornea cause damage directly and they stimulate neutrophil infiltration causing more damage. The result of keratitis is irreversible scarring and a loss in visual acuity or even blindness. Thus, there is a need for new therapies designed to arrest damage as antibiotic therapy kills the bacteria, a benefit that no presently available drugs can offer.

The development of such therapy requires a full understanding of the bacterial products that mediate the damage. Underway are bacterial genetic and biochemical studies to identify such reactive molecules and to seek chemotherapeutic or immunological means to arrest their action. These studies are designed to improve therapy of eye infections and the research employs experimental models particularly well suited to detect and analyze new aspects of bacterial virulence. 

The major ongoing components of this research include:

  • The toxins and the host defense system of the eye are being studied in Staphylococcus aureus keratitis. Among the accomplishments of this research has been the molecular and biochemical characterization of alpha-toxin in keratitis and use of antibody or chemical inhibitors to inhibit these reactions. The greatest effort now is on the characterization of a newly discovered corneal toxin.
  • The role of proteases in Pseudomonas aeruginosa keratitis and pneumonia is also a major project. This research led to the discovery of protease IV as a virulence factor and of PASP, another protease that is a corneal virulence factor. The study of Pseudomonas proteases in the virulence of lung infections has become an important and growing aspect of our research. Ongoing is a study of the pathogenesis of pneumonia and of infections among cystic fibrosis patients.

Our research also includes the study of anti-microbial agents in treating and preventing infections. Important to the antibiotic research are new antibiotics as well as the development of new formulations that better deliver drugs to the eye. Animal models of keratitis suitable for quantifying the effectiveness of antibiotic therapy have been developed for Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, and Mycobacterium abscessus. A model for studying the benefits of antibiotic prophylaxis has also been developed and used to quantify the value of specific formulations.

Other activities

  • Member of the American Society for Microbiology, 1965-present.
  • Member of the Association for Research in Vision and Ophthalmology, 1992-present.
  • Reviewer and guest editor for Investigative Ophthalmology and Visual Sciences, 1997-present.
  • Reviewer for Current Eye Research, 1998-present.
  • Reviewer for Cornea, 2002-present.
  • Reviewer for Ocular Immunology and Inflammation, 2003-present.