Center for Global Health Faculty

Academic Degrees

Departmental Address

Contact Information

Email:

csears+jhmi.edu

Phone:

410-614-0141

Fax:

410-502-5741

Link:

SciVal Experts Research Profile

Research and Professional Experience

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.

Keywords

• Diarrheal diseases
• food poisoning
• enterotoxigenic Bacteroides fragilis
• Bacteroides fragilis
• Cryptosporidium parvum
• enteric diseases

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.

Selected Publications

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.

Wu S, Powell J, Mathioudakis N, Kane S, Fernandez E, Sears CL. Bacteroides fragilis enterotoxin induces intestinal epithelial cell secretion of interleukin-8 through mitogen-activated protein kinases and a tyrosine kinase-regulated nuclear factor-kappaB pathway. Infect Immun. 2004 Oct;72(10):5832-9.

Spacek LA, Hurley BP, Acheson DWK, Granok A, Currie A, Doing K, Sears CL. Shiga toxin-producing Escherichia coli (STEC) as a possible etiology of chronic diarrhea. 2004 Sep 1;39(5):e46-8. Epub 2004 Aug 11.

Wu S, Morin PJ, Maouyo D, Sears CL. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology 124:392-400, 2003.

Kirkpatrick BD, Daniels MM, Jean SS, Pape JW, Karp C, Littenberg B, Fitzgerald DW, Lederman H, Nataro JP, Sears CL. Cryptosporidiosis stimulates an inflammatory intestinal response in malnourished Haitian children. J Infect Dis. 186:94-101, 2002.

Wu S, Dreyfus LA, Tzianabos AO, Hayashi C, Sears CL. Diversity of the metalloprotease toxin produced by enterotoxigenic Bacteroides fragilis. Infec Immun 70:2463-2471, 2002.

Franco AA, Cheng RK, Goodman A, Polyak C, Sears CL. Modulation of bft expression by the Bacteroides fragilis pathogenicity island and its flanking region. Molecular Microbiology 45:1067-1077, 2002.

Acheson DW, Sears CL. Dangers of empiric oral ciprofloxacin in the treatment of acute inflammatory diarrhea in children. Pediatr Infect Dis J 20:817-818 , 2001.

Newman RD, Lima AAM, Guerrant RL, Sears CL. A prospective longitudinal study of Giardia lamblia infection in north-east Brazilian children. Tropical Medicine and International Health 6:624-634, 2001.

Navarro-Garcia F, Canizalez-Roman A, Luna J, Sears C, Nataro JP. Plasmid-encoded toxin of enteroaggregative Escherichia coli is internalized by epithelial cells. Infec Immun 69:1053-1060, 2001.

Trucksis M, Conn TL, Wasserman SS, Sears CL. The Vibrio Cholerae accessory cholera enterotoxin, Ace, stimulates calcium-dependent chloride and bicarbonate secretion in monolayers of human intestinal epithelial cells (T84 cells) in vitro. Am J Physiol 279: C567-577, 2000.

Sears CL. Molecular Physiology and Pathophysiology of Tight Junctions V. Assault of the tight junction by enteric pathogens. Am J Physiol Gastrointest Liver Physiol 279:G1129-G1134, 2000.