Mark Herzberg

Professor

Diag/Biological Sciences, School of Dentistry

Email: mcherzb@umn.edu
Phone: (612) 625-8404

Education

BA, SUNY Oneonta
MS, CCNY
DDS, New York University
PhD, SUNY Buffalo

Research Interests

The oral mucosa is directly challenged with Human Immunodeficiency Virus (HIV) by exposure of infants to HIV-carrying vaginal fluids at birth and to breast milk postnatally, and with passive oral sex among men. Exposures commonly include both X4 and R5 HIV, yet R5 viruses account for most primary systemic infections. When exposed to HIV and Porphyromas gingivalis cysteine proteases, we hypothesize that oral keratinocytes up-regulate expression of innate immune molecules, including alpha- and beta-defensins and other associated genes, to enhance HIV R5 transcytosis and intracellular resistance to HIV infection. To test this hypothesis, we will: 1. show that expression of CXCR4 and CCR5 by oral keratinocytes contribute to coreceptor-specific transcytosis of X4 and R5 HIV isolates; 2. determine if exposure to HIV regulates expression of the innate immune molecules calprotectin and alpha- and beta-defensins directly or in association with PAR signaling mediated by specific P. gingivalis protease mutants; 3. identify and profile oral keratinocyte innate immune-associated gene expression patterns, including known plausible HIV co-receptors and other innate immune molecules, which are regulated by HIV in the presence and absence of P. gingivalis proteases; and 4 show how innate immune molecules modulate transcytosis, translocation by paracellular routes, and anti-HIV resistance in oral keratinocytes in vitro. This project will show that oral keratinocytes express innate immune molecules to resist intracellular infection by X4 and R5 HIV. In the presence of cysteine proteases, innate immune molecules and genes required for transcytosis ofR5 HIV expression will be up-regulated, increasing intracellular anti-HIV resistance and facilitating transfer R5 HIV-1 to initiate systemic infection. Innate immune factor-related genes may prove to be novel targets
to prevent mucosal HIV.

Selected Recent Publications

(Note: new to HIV research)

• Nobbs AH, Zhang Y, Khammanivong A, Herzberg MC. 2007. Streptococcus gordonii Hsa environmentally constrains competitive binding by Streptococcus sanguinis to saliva-coated hydroxyapatite. J Bacteriol. 2007 Feb 2; [Epub ahead of print].
• Herzberg MC, Griffith LG, Doyle MJ. 2006. Driving the future of dental research. J Dent Res. 85(6):486-7.
• Herzberg MC, Weinberg A, Wahl SM.2006. (C3) The oral epithelial cell and first encounters with HIV-1. Adv Dent Res. 19(1):158-66.
• Kumar RB, Maher DM, Herzberg MC, Southern PJ. 2006. Expression of HIV receptors, alternate receptors and co-receptors on tonsillar epithelium: implications for HIV binding and primary oral infection. Virol J. 3:25.
• Kuboniwa M, Tribble GD, James CE, Kilic AO, Tao L, Herzberg MC, Shizukuishi S, Lamont RJ. 2006. Streptococcus gordonii utilizes several distinct gene functions to recruit Porphyromonas gingivalis into a mixed community. Mol Microbiol. 60(1):121-39.
• Herzberg MC, Nobbs A, Tao L, Kilic A, Beckman E, Khammanivong A, Zhang Y. 2005. Oral streptococci and cardiovascular disease: searching for the platelet aggregation-associated protein gene and mechanisms of Streptococcus sanguis-induced thrombosis. J Periodontol. 76(11 Suppl):2101-5.
• Gong K., MacFarlane G.D., Costalonga M., Ross K.F., & Herzberg, M.C. 2005. Inactivation of Streptococcus gordonii SspAB alters expression of multiple adhesin genes.. Infect Immun. 73(6):3351-7.
• Kilic AO, Tao L, Zhang Y, Lei Y, Khammanivong A, Herzberg MC. 2004. Involvement of Streptococcus gordonii beta-glucoside metabolism systems in adhesion, biofilm formation, and in vivo gene expression. J Bacteriol. 186:4246-53.
• Zhang Y, Lei Y, Khammanivong A, Herzberg MC. 2004. Identification of a novel two-component system in Streptococcus gordonii V288 involved in biofilm formation. Infect Immun. 2004 Jun;72(6):3489-94.
• Basi DL, Ross KF, Hodges JS, Herzberg MC. 2003. The modulation of tissue factor by endothelial cells during heat shock. J Biol Chem. 278:11065-71.
• Costalonga M, Hodges JS, Herzberg MC. 2002. Streptococcus sanguis modulates type II collagen-induced arthritis in DBA/1J mice. J Immunol. 169:2189-95.
• Herzberg MC. 2001. Coagulation and thrombosis in cardiovascular disease: plausible contributions of infectious agents. Ann Periodontol. 6:16-9. Review.
• Yokota M, Basi DL, Herzberg MC, Meyer MW. 2001. Anti-fibrin antibody binding in valvular vegetations and kidney lesions during experimental endocarditis. Microbiol Immunol. 45:699-707.
• Nisapakultorn K, Ross KF, Herzberg MC. 2001. Calprotectin expression in vitro by oral epithelial cells confers resistance to infection by Porphyromonas gingivalis. Infect Immun. 69:4242-7.
• Nisapakultorn K, Ross KF, Herzberg MC. 2001. Calprotectin expression inhibits bacterial binding to mucosal epithelial cells. Infect Immun. 69:3692-6.
• Ross KF, Herzberg MC. 2001. Calprotectin expression by gingival epithelial cells. Infect Immun. 2001 May;69(5):3248-54.
• Gong K, Mailloux L, Herzberg MC. 2000. Salivary film expresses a complex, macromolecular binding site for Streptococcus sanguis. J Biol Chem. 275:8970-4.