Keywords
Last Name

Eva Helmerhorst, PhD

TitleAssociate Professor
InstitutionBoston University Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology
Address700 Albany St Ctr for Adv Biomed Res
Boston MA 02118
Phone(617) 414-1119
ORCID ORCID Icon0000-0002-4803-3018
Other Positions
TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine, Graduate Medical Sciences

 Awards and Honors

Start-EndDescription
1998Colgate-Palmolive, NY, NY: Colgate Research in Prevention Award
2000Interuniversitaire Onderzoeksschool Tandheelkunde (Netherlands): Bohn Stafleu Van Loghem-Thoden van Velzen Award
2002MRC Dunn Human Nutrition Unit: Collaboration with Dr. John Walker, Nobel laureate
2012United European Gastroenterology week: Best Oral Presentation in Session
2013Salivary Research Group, IADR: Salivary Researcher of the Year
 Research Expertise & Professional Interests
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.



 Self-Described Keywords
  • Antifungal
  • Candidiasis
  • Celiac
  • Cross-linking
  • Degradation
  • Dental
  • Enzymes
  • Gastrointestinal
  • Histatins
  • LC-ESI-MS/MS
  • Oral
  • Pellicle
  • Proline-rich
  • Proteins
  • Proteolytic
  • Proteome
  • Saliva
  • Transglutaminase
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Tian N, Wei G, Schuppan D, Helmerhorst EJ. Effect of Rothia mucilaginosa enzymes on gliadin (gluten) structure, deamidation, and immunogenic epitopes relevant to celiac disease. Am J Physiol Gastrointest Liver Physiol. 2014 Oct 15; 307(8):G769-76.
    View in: PubMed
  2. Trindade F, Oppenheim FG, Helmerhorst EJ, Amado F, Gomes PS, Vitorino R. Uncovering the molecular networks in periodontitis. Proteomics Clin Appl. 2014 Oct; 8(10):748-61.
    View in: PubMed
  3. Iavarone F, D''Alessandro A, Tian N, Cabras T, Messana I, Helmerhorst EJ, Oppenheim FG, Castagnola M. High-resolution high-performance liquid chromatography with electrospray ionization mass spectrometry and tandem mass spectrometry characterization of a new isoform of human salivary acidic proline-rich proteins named Roma-Boston Ser22 (Phos) ? Phe variant. J Sep Sci. 2014 Jul; 37(14):1896-902.
    View in: PubMed
  4. Vukosavljevic D, Hutter JL, Helmerhorst EJ, Xiao Y, Custodio W, Zaidan FC, Oppenheim FG, Siqueira WL. Nanoscale Adhesion Forces between Enamel Pellicle Proteins and Hydroxyapatite. J Dent Res. 2014 May; 93(5):514-9.
    View in: PubMed
  5. Fernandez-Feo M, Wei G, Blumenkranz G, Dewhirst FE, Schuppan D, Oppenheim FG, Helmerhorst EJ. The cultivable human oral gluten-degrading microbiome and its potential implications in coeliac disease and gluten sensitivity. Clin Microbiol Infect. 2013 Sep; 19(9):E386-94.
    View in: PubMed
  6. Oppenheim FG, Helmerhorst EJ, Lendenmann U, Offner GD. Anti-candidal activity of genetically engineered histatin variants with multiple functional domains. PLoS One. 2012; 7(12):e51479.
    View in: PubMed
  7. Zamakhchari M, Wei G, Dewhirst F, Lee J, Schuppan D, Oppenheim FG, Helmerhorst EJ. Identification of Rothia bacteria as gluten-degrading natural colonizers of the upper gastro-intestinal tract. PLoS One. 2011; 6(9):e24455.
    View in: PubMed
  8. Thomadaki K, Helmerhorst EJ, Tian N, Sun X, Siqueira WL, Walt DR, Oppenheim FG. Whole-saliva proteolysis and its impact on salivary diagnostics. J Dent Res. 2011 Nov; 90(11):1325-30.
    View in: PubMed
  9. Komatsu T, Salih E, Helmerhorst EJ, Offner GD, Oppenheim FG. Influence of histatin 5 on Candida albicans mitochondrial protein expression assessed by quantitative mass spectrometry. J Proteome Res. 2011 Feb 4; 10(2):646-55.
    View in: PubMed
  10. 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; 5(10):e13264.
    View in: PubMed
  11. 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 Oct 1; 9(10):5413-21.
    View in: PubMed
  12. Hanasab H, Jammal D, Oppenheim FG, Helmerhorst EJ. The antifungal activity of human parotid secretion is species-specific. Med Mycol. 2011 Feb; 49(2):218-21.
    View in: PubMed
  13. Salih E, Siqueira WL, Helmerhorst EJ, Oppenheim FG. Large-scale phosphoproteome of human whole saliva using disulfide-thiol interchange covalent chromatography and mass spectrometry. Anal Biochem. 2010 Dec 1; 407(1):19-33.
    View in: PubMed
  14. Siqueira WL, Margolis HC, Helmerhorst EJ, Mendes FM, Oppenheim FG. Evidence of intact histatins in the in vivo acquired enamel pellicle. J Dent Res. 2010 Jun; 89(6):626-30.
    View in: PubMed
  15. Bosch JA, de Geus EJ, Carroll D, Goedhart AD, Anane LA, van Zanten JJ, Helmerhorst EJ, Edwards KM. A general enhancement of autonomic and cortisol responses during social evaluative threat. Psychosom Med. 2009 Oct; 71(8):877-85.
    View in: PubMed
  16. Sun X, Salih E, Oppenheim FG, Helmerhorst EJ. Activity-based mass spectrometric characterization of proteases and inhibitors in human saliva. Proteomics Clin Appl. 2009 Jul 1; 3(7):810-820.
    View in: PubMed
  17. 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 Aug; 23(8):2691-701.
    View in: PubMed
  18. Blicharz TM, Siqueira WL, Helmerhorst EJ, Oppenheim FG, Wexler PJ, Little FF, Walt DR. Fiber-optic microsphere-based antibody array for the analysis of inflammatory cytokines in saliva. Anal Chem. 2009 Mar 15; 81(6):2106-14.
    View in: PubMed
  19. White MR, Helmerhorst EJ, Ligtenberg A, Karpel M, Tecle T, Siqueira WL, Oppenheim FG, Hartshorn KL. Multiple components contribute to ability of saliva to inhibit influenza viruses. Oral Microbiol Immunol. 2009 Feb; 24(1):18-24.
    View in: PubMed
  20. Campese M, Sun X, Bosch JA, Oppenheim FG, Helmerhorst EJ. Concentration and fate of histatins and acidic proline-rich proteins in the oral environment. Arch Oral Biol. 2009 Apr; 54(4):345-53.
    View in: PubMed
  21. Blicharz TM, Rissin DM, Bowden M, Hayman RB, DiCesare C, Bhatia JS, Grand-Pierre N, Siqueira WL, Helmerhorst EJ, Loscalzo J, Oppenheim FG, Walt DR. Use of colorimetric test strips for monitoring the effect of hemodialysis on salivary nitrite and uric acid in patients with end-stage renal disease: a proof of principle. Clin Chem. 2008 Sep; 54(9):1473-80.
    View in: PubMed
  22. 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 Jul 18; 283(29):19957-66.
    View in: PubMed
  23. Siqueira WL, Salih E, Wan DL, Helmerhorst EJ, Oppenheim FG. Proteome of human minor salivary gland secretion. J Dent Res. 2008 May; 87(5):445-50.
    View in: PubMed
  24. Helmerhorst EJ, Oppenheim FG. Saliva: a dynamic proteome. J Dent Res. 2007 Aug; 86(8):680-93.
    View in: PubMed
  25. Siqueira WL, Zhang W, Helmerhorst EJ, Gygi SP, Oppenheim FG. Identification of protein components in in vivo human acquired enamel pellicle using LC-ESI-MS/MS. J Proteome Res. 2007 Jun; 6(6):2152-60.
    View in: PubMed
  26. Helmerhorst EJ. Whole saliva proteolysis: wealth of information for diagnostic exploitation. Ann N Y Acad Sci. 2007 Mar; 1098:454-60.
    View in: PubMed
  27. Walt DR, Blicharz TM, Hayman RB, Rissin DM, Bowden M, Siqueira WL, Helmerhorst EJ, Grand-Pierre N, Oppenheim FG, Bhatia JS, Little FF, Brody JS. Microsensor arrays for saliva diagnostics. Ann N Y Acad Sci. 2007 Mar; 1098:389-400.
    View in: PubMed
  28. Siqueira WL, Helmerhorst EJ, Zhang W, Salih E, Oppenheim FG. Acquired enamel pellicle and its potential role in oral diagnostics. Ann N Y Acad Sci. 2007 Mar; 1098:504-9.
    View in: PubMed
  29. Oppenheim FG, Salih E, Siqueira WL, Zhang W, Helmerhorst EJ. Salivary proteome and its genetic polymorphisms. Ann N Y Acad Sci. 2007 Mar; 1098:22-50.
    View in: PubMed
  30. Helmerhorst EJ, Alagl AS, Siqueira WL, Oppenheim FG. Oral fluid proteolytic effects on histatin 5 structure and function. Arch Oral Biol. 2006 Dec; 51(12):1061-70.
    View in: PubMed
  31. Piludu M, Lantini MS, Cossu M, Piras M, Oppenheim FG, Helmerhorst EJ, Siqueira W, Hand AR. Salivary histatins in human deep posterior lingual glands (of von Ebner). Arch Oral Biol. 2006 Nov; 51(11):967-73.
    View in: PubMed
  32. Helmerhorst EJ, Venuleo C, Sanglard D, Oppenheim FG. Roles of cellular respiration, CgCDR1, and CgCDR2 in Candida glabrata resistance to histatin 5. Antimicrob Agents Chemother. 2006 Mar; 50(3):1100-3.
    View in: PubMed
  33. Helmerhorst EJ, Venuleo C, Beri A, Oppenheim FG. Candida glabrata is unusual with respect to its resistance to cationic antifungal proteins. Yeast. 2005 Jul 15; 22(9):705-14.
    View in: PubMed
  34. Helmerhorst EJ, Stan M, Murphy MP, Sherman F, Oppenheim FG. The concomitant expression and availability of conventional and alternative, cyanide-insensitive, respiratory pathways in Candida albicans. Mitochondrion. 2005 Jun; 5(3):200-11.
    View in: PubMed
  35. Mendelsohn RD, Helmerhorst EJ, Cipollo JF, Kukuruzinska MA. A hypomorphic allele of the first N-glycosylation gene, ALG7, causes mitochondrial defects in yeast. Biochim Biophys Acta. 2005 May 25; 1723(1-3):33-44.
    View in: PubMed
  36. Li J, Helmerhorst EJ, Yao Y, Nunn ME, Troxler RF, Oppenheim FG. Statherin is an in vivo pellicle constituent: identification and immuno-quantification. Arch Oral Biol. 2004 May; 49(5):379-85.
    View in: PubMed
  37. Helmerhorst EJ, Flora B, Troxler RF, Oppenheim FG. Dialysis unmasks the fungicidal properties of glandular salivary secretions. Infect Immun. 2004 May; 72(5):2703-9.
    View in: PubMed
  38. Ahmad M, Piludu M, Oppenheim FG, Helmerhorst EJ, Hand AR. Immunocytochemical localization of histatins in human salivary glands. J Histochem Cytochem. 2004 Mar; 52(3):361-70.
    View in: PubMed
  39. Li J, Helmerhorst EJ, Troxler RF, Oppenheim FG. Identification of in vivo pellicle constituents by analysis of serum immune responses. J Dent Res. 2004 Jan; 83(1):60-4.
    View in: PubMed
  40. Li J, Helmerhorst EJ, Leone CW, Troxler RF, Yaskell T, Haffajee AD, Socransky SS, Oppenheim FG. Identification of early microbial colonizers in human dental biofilm. J Appl Microbiol. 2004; 97(6):1311-8.
    View in: PubMed
  41. Gusman H, Leone C, Helmerhorst EJ, Nunn M, Flora B, Troxler RF, Oppenheim FG. Human salivary gland-specific daily variations in histatin concentrations determined by a novel quantitation technique. Arch Oral Biol. 2004 Jan; 49(1):11-22.
    View in: PubMed
  42. Li J, Helmerhorst EJ, Corley RB, Luus LE, Troxler RF, Oppenheim FG. Characterization of the immunologic responses to human in vivo acquired enamel pellicle as a novel means to investigate its composition. Oral Microbiol Immunol. 2003 Jun; 18(3):183-91.
    View in: PubMed
  43. Helmerhorst EJ, Murphy MP, Troxler RF, Oppenheim FG. Characterization of the mitochondrial respiratory pathways in Candida albicans. Biochim Biophys Acta. 2002 Oct 3; 1556(1):73-80.
    View in: PubMed
  44. Murakami Y, Xu T, Helmerhorst EJ, Ori G, Troxler RF, Lally ET, Oppenheim FG. Inhibitory effect of synthetic histatin 5 on leukotoxin from Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol. 2002 Jun; 17(3):143-9.
    View in: PubMed
  45. Rothstein DM, Helmerhorst EJ, Spacciapoli P, Oppenheim FG, Friden P. Histatin-derived peptides: potential agents to treat localised infections. Expert Opin Emerg Drugs. 2002 May; 7(1):47-59.
    View in: PubMed
  46. Helmerhorst EJ, Troxler RF, Oppenheim FG. The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. Proc Natl Acad Sci U S A. 2001 Dec 4; 98(25):14637-42.
    View in: PubMed
  47. Flora B, Gusman H, Helmerhorst EJ, Troxler RF, Oppenheim FG. A new method for the isolation of histatins 1, 3, and 5 from parotid secretion using zinc precipitation. Protein Expr Purif. 2001 Oct; 23(1):198-206.
    View in: PubMed
  48. Gyurko C, Lendenmann U, Helmerhorst EJ, Troxler RF, Oppenheim FG. Killing of Candida albicans by histatin 5: cellular uptake and energy requirement. Antonie Van Leeuwenhoek. 2001 Sep; 79(3-4):297-309.
    View in: PubMed
  49. Ruissen AL, Groenink J, Helmerhorst EJ, Walgreen-Weterings E, Van't Hof W, Veerman EC, Nieuw Amerongen AV. Effects of histatin 5 and derived peptides on Candida albicans. Biochem J. 2001 Jun 1; 356(Pt 2):361-8.
    View in: PubMed
  50. van 't Hof W, Veerman EC, Helmerhorst EJ, Amerongen AV. Antimicrobial peptides: properties and applicability. Biol Chem. 2001 Apr; 382(4):597-619.
    View in: PubMed
  51. Gusman H, Travis J, Helmerhorst EJ, Potempa J, Troxler RF, Oppenheim FG. Salivary histatin 5 is an inhibitor of both host and bacterial enzymes implicated in periodontal disease. Infect Immun. 2001 Mar; 69(3):1402-8.
    View in: PubMed
  52. Helmerhorst EJ, van't Hof W, Breeuwer P, Veerman EC, Abee T, Troxler RF, Amerongen AV, 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 Feb 23; 276(8):5643-9.
    View in: PubMed
  53. van't Hof W, Reijnders IM, Helmerhorst EJ, Walgreen-Weterings E, Simoons-Smit IM, Veerman EC, Amerongen AV. Synergistic effects of low doses of histatin 5 and its analogues on amphotericin B anti-mycotic activity. Antonie Van Leeuwenhoek. 2000 Aug; 78(2):163-9.
    View in: PubMed
  54. Helmerhorst EJ, Hodgson R, van 't Hof W, Veerman EC, Allison C, Nieuw Amerongen AV. The effects of histatin-derived basic antimicrobial peptides on oral biofilms. J Dent Res. 1999 Jun; 78(6):1245-50.
    View in: PubMed
  55. Helmerhorst EJ, Reijnders IM, van 't Hof W, Veerman EC, Nieuw Amerongen AV. A critical comparison of the hemolytic and fungicidal activities of cationic antimicrobial peptides. FEBS Lett. 1999 Apr 23; 449(2-3):105-10.
    View in: PubMed
  56. Helmerhorst EJ, Breeuwer P, van't Hof W, Walgreen-Weterings E, Oomen LC, Veerman EC, Amerongen AV, Abee T. The cellular target of histatin 5 on Candida albicans is the energized mitochondrion. J Biol Chem. 1999 Mar 12; 274(11):7286-91.
    View in: PubMed
  57. Helmerhorst EJ, Reijnders IM, van't Hof W, Simoons-Smit I, Veerman EC, 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 Mar; 43(3):702-4.
    View in: PubMed
  58. Helmerhorst EJ, Maaskant JJ, Appelmelk BJ. Anti-lipid A monoclonal antibody centoxin (HA-1A) binds to a wide variety of hydrophobic ligands. Infect Immun. 1998 Feb; 66(2):870-3.
    View in: PubMed
  59. Helmerhorst EJ, Van't Hof W, Veerman EC, Simoons-Smit I, Nieuw Amerongen AV. Synthetic histatin analogues with broad-spectrum antimicrobial activity. Biochem J. 1997 Aug 15; 326 ( Pt 1):39-45.
    View in: PubMed
  60. Appelmelk BJ, Qing AY, Helmerhorst EJ, Maaskant JJ, Abraham PR, Thijs LG, MacLaren DM. Diversity in lipid A binding ligands: comparison of lipid A monoclonal antibodies with rBPI23. Prog Clin Biol Res. 1995; 392:453-63.
    View in: PubMed
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