B.S., Pennsylvania State University; M.D., Thomas Jefferson Medical College
Our research area of focus is the pathogenesis of enteric infections, specifically enterotoxigenic Bacteroides fragilis (ETBF) and Cryptosporidium parvum. In the laboratory located at JHU SOM, we investigate the mechanisms of action of the B. fragilis toxin (BFT) and ETBF using eukaryotic cell lines and mouse models of disease. These studies have identified that BFT and ETBF stimulate marked proinflammatory and proliferative responses both in cells in vitro and in the mouse colon. We presently seek to identify the BFT receptor and the early steps in disease as well as long term sequelae of ETBF infection.
In the field, we pursue translational studies to understand the pathogenesis of ETBF disease and disease due to Cryptosporidium parvum. Previous studies have been conducted in Brazil and Haiti; currently we conduct studies in Dhaka, Bangladesh at the International Centre for Diarrheal Diseases Research-Centre for Health and Population Research. Our studies of ETBF have identified that these organisms are associated with inflammatory diarrhea, similar to Shigella spp. Ongoing studies are characterizing the host response to ETBF infection as well as evaluating ETBF genetic and pathogenetic heterogeneity. Studies of Cryptosporidium parvum conducted initially in Haiti and Brazil indicate this parasite stimulates iintestinal inflammation when causing disease in young children and is associated with growth faltering. Ongoing studies in Dhaka conducted by Dr. Beth Kirkpatrick (University of Vermont) pursue the immunopathogenesis of C. parvum infection in young children.
Honors and Awards
Alpha Omega Alpha, 1975 Membership in the American Society for Clinical Investigation, May, 1996. Bacteriology and Mycology II Study Section, Permanent member, 1998-2002 Clinical Infectious Diseases, Associate Editor. January, 2000 - Present.
enterotoxigenic Bacteroides fragilis
Bushen OY, Kholi A, Pinkerton RC, Newman RD, Sears CL, Fayer R, Lima AAM, Guerrant RL. Heavy cryptosporidial infections in children in northeast Brazil: Comparison of C. hominis and C. parvum (in press).
Kirkpatrick BD, Wagner D, Noel F, Rouzier P, Pape JW, Alston WK, Larsson CJ, Powden C, O’Neill JP, Sears CL. Mannose-binding lectin deficiency is associated with cryptosporidiosis and male gender in young Haitian children (in press).
Kirkpatrick BD, Noel F, Rouzier PD, Powell J, Pape JW, Bois G, Alston WK, Larsson CJ, Tenney K, Ventrone C, Powden C, Sreenivasan M, Sears CL. Childhood cryptosporidiosis is associated with a persistent systemic inflammatory response (in press).
Sears CL. A Dynamic Partnership: Celebrating our Gut Flora. Anaerobe 11:247-251, 2005.
Franco AA, Buckwold S, Shin JW, Ascon M, Sears CL. Mutation of the zinc-binding metalloprotease motif affects Bacteroides fragilis toxin activity without affecting propeptide processing. Infect Immun 73:5273-7, 2005.