Associate Professor, Department of Molecular & Cell Biology
700 Albany Street
Boston, MA 02118 USA
MS, Vrije Universiteit, Amsterdam (The Netherlands)
PhD, Academic Centre for Dentistry (ACTA), Amsterdam (The Netherlands)
Research by Helmerhorst and coworkers is focusing on the role of the microbiome of the upper gastro-intestinal tract, the oral cavity, in the digestion of dietary gluten. Dietary gluten comprise a family of proteins that are abundantly present in the Western diet. Gluten proteins are fairly difficult to digest because of their unusual amino acid content and -sequence. In genetically predisposed individuals, gluten proteins elicit an auto-immune response leading to the destruction of the villi of the small intestine thus interfering with efficient uptake of nutrients causing celiac disease. The predominant amino acids in the gluten sequences are proline (Pro) and glutamine (Gln). Our recent investigations indicate that human saliva contains unique enzymes that can cleave the peptide bond C-terminal to the Xaa-Pro-Gln sequence. This tripeptide is prevalent in T-cell stimulatory gluten domains. While the human digestive enzyme system apparently lacks the capacity to neutralize essential immunogenic gluten domains implicated in celiac disease, such activities are naturally present in the oral microbial proteasome. These novel findings offer clinical insights as well as therapeutic perspectives for the treatment of celiac disease.
Helmerhorst EJ, Zamakhchari M, Schuppan D, Oppenheim FG. Discovery of a novel and rich source of gluten-degrading microbial enzymes in the oral cavity. PLoS One. 2010. In press.
Helmerhorst EJ, Traboulsi G, Salih E, Oppenheim FG. Mass spectrometric identification of key proteolytic cleavage sites in statherin affecting mineral homeostasis and bacterial binding domains. J Proteome Res. 2010. 9:5413-21.
Sun X, Salih E, Oppenheim FG, Helmerhorst EJ. Activity-based mass spectrometric characterization of proteases and inhibitors in human saliva. Proteomics Clin Appl. 2009. 3:810-820.
Sun X, Salih E, Oppenheim FG, Helmerhorst EJ. Kinetics of histatin proteolysis in whole saliva and the effect on bioactive domains with metal-binding, antifungal, and wound-healing properties. FASEB J. 2009. 23:2691-701.
Helmerhorst EJ, Sun X, Salih E, Oppenheim FG. Identification of Lys-Pro-Gln as a novel cleavage site specificity of saliva-associated proteases. J Biol Chem. 2008. 283:19957-66.
Helmerhorst EJ, Oppenheim FG. Saliva: a dynamic proteome. J Dent Res. 2007. 86: 680-693. Oppenheim FG, Salih E, Siqueira WL, Zhang W, Helmerhorst EJ. The salivary proteome and its genetic polymorphisms. Annals NY Acad Sci. 2007. 1098: 22-50.
Helmerhorst EJ, Alagl AS, Siqueira WL, Oppenheim FG. Oral fluid proteolytic effects on histatin 5 structure and function. Arch Oral Biol. 2006. 51:1061-1070.
Li J, Helmerhorst EJ, Leone CW, Troxler RF, Yaskell T, Haffajee AD, Socransky SS and Oppenheim FG. Identification of early microbial colonizers in human dental biofilm. J Appl Microbiol 2004. 97:1311-18.
Helmerhorst EJ, Murphy MP, Troxler RF and Oppenheim FG. Characterization of the mitochondrial respiratory pathways in Candida albicans. Biochim Biophys Acta 2002. 1556:73-80.
Helmerhorst EJ, Troxler RF and Oppenheim FG. The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. Proc Nat Acad Sci USA 2001. 98:14637-42.
Helmerhorst EJ, Van ‘t Hof W, Breeuwer P, Veerman EI, Abee T, Troxler RF, Nieuw Amerongen AV and Oppenheim FG. Characterization of histatin 5 with respect to amphipathicity, hydrophobicity and effects on cell and mitochondrial membrane integrity excludes a candidacidal mechanism of pore formation. J Biol Chem 2001. 276:5643-5649.
Helmerhorst EJ, Breeuwer P, Van ‘t Hof W, Walgreen-Weterings E, Oomen LCJM, Veerman ECI, Nieuw Amerongen AV and Abee T. The cellular target of histatin 5 on Candida albicans is the energized mitochondrion. J Biol Chem 1999. 274:7286-91.
Helmerhorst EJ, Reijnders IM, Van ‘t Hof W, Simoons-Smit AM, Veerman EI and Nieuw Amerongen AV. Amphotericin B and fluconazole-resistant Candida spp., Aspergillus fumigatus, and other newly emerging pathogenic fungi are susceptible to basic antifungal peptides. Antimicrob Agents Chemother 1999. 43:702-704.
Helmerhorst EJ, Hodgson R, Van ‘t Hof W, Veerman EI, Allison C and Nieuw Amerongen AV. The effect of histatin-derived antimicrobial peptides on oral bio¬films. J Dent Res 1999. 78:1245-50.
Helmerhorst EJ, van ‘t Hof W, Simoons-Smit AM, Veerman EI and Nieuw Amerongen AV. Synthetic histatin analogs with broad spectrum antimicrobial activity. Biochem J 1997. 326:39-45.
NIH/NIAID Grant AI087803 (R01): “Gastro-Intestinal Microbes Degrading Dietary Gluten”. Role: Principal Investigator.
NIH/NIDCR Grant DE18132 (R21): “Oral Fluid Proteolytic Effects on Salivary Protein Structure and Function”. Role: Principal Investigator.
NIH/NIDCR Grant DE07652 (R01): “Microbicidal Salivary Histidine-rich Proteins”. Role: Co-Investigator.
NIH/NIDCR Grant DE05672 (R01): “Salivary Proteins in Dental Integuments”. Role: Co-Investigator.