novel antigen discovery

The identification of conserved antigens expressed by a majority of ETEC strains is central to the development of a broadly protective and cost effective vaccine. High throughput genomic characterization of many strains combined with unbiased “open- aperture” investigation of the global ETEC immunoproteome have highlighted conserved highly immunogenic antigens currently under investigation as ETEC vaccine antigens. With partners here, at icddrb, and Scripps we are currently working to identify critical epitopes of these molecules recognized during the course of infection to refine their use in vaccines.


Investigating molecular mechanisms of ETEC pathogen-host interactions | Elucidation of virulence molecules essential to effective delivery of LT and ST enterotoxins can pinpoint potential targets for neutralization by vaccines. Recent studies have shown that molecules secreted by ETEC can play important roles in interaction with intestinal epithelia. These include the EtpA adhesin which interacts with A blood group sugars on enterocytes, and EatA a protease that degrades intestinal mucin to promote access of the bacteria to target host cells.


Investigation of the consequences of ETEC-pathogen host interactions | Evidence has continued to accumulate that ETEC infections are associated with damage to the small intestine that persists long after the acute infection and diarrhea have resolved. Both ST and LT toxins drive accumulation of “second messenger” cyclic nucleotides in the cell that govern many cellular pathways. The laboratory is currently attempting to understand cellular changes that occur following intoxication with LT and ST to define molecular events underlying sequelae including malnutrition that follow ETEC infections.