Mark Herzberg, DDS, PhD

Mark Herzberg is Professor, Department of Diagnostic and Biological Sciences, Director Emeritus of the NIH-supported Minnesota Craniofacial Research Training Program (MinnCResT) at the School of Dentistry, and former Associate Director of the University of Minnesota Clinical and Translational Science Institute at the University of Minnesota. He directs a research program focused on host-microbial interactions, with a serendipitous diversion into cancer biology. Conducted with his students and postdoctoral fellows, research from the Herzberg lab has been the subject of numerous research reports published in the peer-reviewed literature.

Mark obtained his BA in literature in 1967 from the State University College, Oneonta, NY, an MS in English Education in 1969 from the City College of New York, his DDS degree in 1973 from New York University, and PhD in Oral Biology and a Specialty Certificate in Periodontics from the State University of New York at Buffalo in 1978.  Mark has held Visiting Fellow and Professorial positions at research institutions world-wide and served on numerous NIH review panels and advisory groups.  In 1992, he was elected Fellow for the American Association for the Advancement of Science and in 1995 he received the Distinguished Scientist Award in Oral Biology from the International Association for Dental Research, served as editor of the Journal of Dental Research from 1993 to 2004, and in 2018, Mark was elected Vice President of the American Association for Dental Research and currently serves as Recent Past President (2021-2022).

During his terms as AADR President and Recent Past President, the Association adapted to the challenges of COVID-19.  Meetings were held virtually and then in hybrid formats. In collaboration with our research community, A COVID-19 Rapid-Response Research Agenda (JDR Clin Trans Res. 2020 Oct;5(4):293-296. doi: 10.1177/2380084420930683) was published, which contributed to direct discussions with National Institute of Dental and Craniofacial Research leadership followed by new COVID-related research initiatives. During his presidency, Mark testified on behalf of AADR during a Public Witness hearing convened by House Labor, Health and Human Services, Education and Related Agencies (Labor-HHS) Appropriations Subcommittee. He advocated for increased funding for the NIDCR and the NIH in fiscal year 2022 spending legislation. Mark shared how the research enterprise had been negatively impacted by the COVID-19 pandemic and how the NIDCR, even without receiving targeted federal coronavirus relief funding, skillfully pivoted to support coronavirus research.

At the University of Minnesota, as director and now director emeritus of MinnCResT, I contributed to career development for our many trainees supported first by our institutional T32 program in 1996, which was superseded by our current T90/R90 grant.  In my own research program, I have been primary mentor to more than 20 aspiring independent investigators (PhD students, postdoctoral fellows, and young faculty), many of whom are dentists.  All now enjoy careers in research, academics, and patient care

Much of my research activity through the years has focused on host-microbial interactions from the vantage point of the microbial biofilm and the innate host response.  I trained as a structural biochemist, which has guided our studies of streptococcal adhesion mechanisms in our lab for more than 30 years. We have pioneered in vitro and in vivo approaches to characterize structure-function relationships important in streptococcal-platelet interactions and innate epithelial immunity, as well as in vitro modeling of oral streptococcal biology in vivo. Our interest in gene regulation in streptococci during biofilm formation dates back more than 15 years, when we made seminal observations that suggested that binding to a salivary substrate could change adhesin gene expression. Several fine postdocs and collaborators contributed to the conduct of these studies. We have steadfastly worked toward more robust evidence to support the hypothesis that the streptococci respond to the surface environment and adjust the presentation of surface proteins (adhesins).  And we now show that S. gordonii responds to surface environmental cues using a newly discovered outside-in signaling mechanism involving the paired adhesins SspAB, lipoteichoic acid and an intramembrane two-component system, SraSR.  The mechanism regulates the expression of MbpA, a MUC5B-binding LPXTG-adhesin. Our studies in innate immune proteins led to the serendipitous observation that antimicrobial calprotectin (S100A8/A9) also behaves as a tumor suppressor.  Recently, we reported that S100A8/A9 is downregulated in clinical cases of head and neck cancer and may impact survival.  Our published in vitro and in vivo mechanistic studies explain the tumor suppressive mechanism of S100A8/A9 in oral cancer.  We are pursuing studies to learn whether mRNA transfections can effectively augment translation of S100A8/A9 in epithelial cells and tissues, which we are testing for suppression of tumor formation in vivo.

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.

Award: Treatment of cancer pain by lipid mediator Resolvin D1:
Principal Investigator: Khasabov, Serhii
Sponsoring Organization: NIH NATIONAL CANCER INSTITUTE (NCI)
Award Dates: 2021 - 2026
 

Award: Calprotectin-mediated CD69 signaling in periodontitis
Principal Investigator: Costalonga, Massimo
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2021 - 2026
 

Award: Calprotectin and CD69 affect regulatory T cell responses
Principal Investigator: Costalonga, Massimo
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2021 - 2023

Award: A novel, two-armed autotherapy for mucosal infectious di
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2020 - 2022

Award: Regulation of Surface Protein Presentation on Streptococ
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2018 - 2019
 

Award: Regulation of Surface Protein Presentation on Streptococ
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2018
 

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2022
 

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2022

Award: Minnesota Craniofacial Research Training Program - R90
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2022

Award: Minnesota Craniofacial Research Training Program - R90
Principal Investigator: Mansky, Kim
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2017 - 2022

Award: Regulation of Surface Protein Presentation on Streptococ
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2019

Award: Regulation of Surface Protein Presentation on Streptococ
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2022
 

Award: Calprotectin in oral innate immunity
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2018

Award: Minnesota Craniofacial Research Training Grant
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2017

Award: Minnesota Craniofacial Research Training Grant
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2017

Award: Minnesota Craniofacial Research Training R-90
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2017

Award: Minnesota Craniofacial Research Training R-90
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2016 - 2017

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2012 - 2016

Award: Minnesota Craniofacial Research Training Program - R90
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2012 - 2016

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2012 - 2016

Award: Minnesota Craniofacial Research Training Program - R90
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2012 - 2016

Award: University of Minnesota Clinical and Translational Scien
Principal Investigator: Blazar, Bruce R
Sponsoring Organization: NIH Nat'l Center for Research Resources
Award Dates: 2011 - 2017
 

Award: University of Minnesota Clinical and Translational Scien
Principal Investigator: Blazar, Bruce R
Sponsoring Organization: NIH Nat'l Center for Research Resources
Award Dates: 2011 - 2017

Award: University of Minnesota Clinical and Translational Scien
Principal Investigator: Blazar, Bruce R
Sponsoring Organization: NIH Nat'l Center for Research Resources
Award Dates: 2011 - 2017

Award: University of Minnesota Clinical and Translational Scien
Principal Investigator: Blazar, Bruce R
Sponsoring Organization: NIH Nat'l Center for Research Resources
Award Dates: 2011 - 2017
 

Award: Augmenting Innate Immunity to Protect the Oral Mucosa
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2010 - 2015

Award: Transmission Electron Microscope in the Academic Health
Principal Investigator: Zhang, Wei
Sponsoring Organization: NIH Nat'l Center for Research Resources
Award Dates: 2010 - 2012

Award: S. sanguis Adhesion: Molecular Basis of Specificity
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2005 - 2012

Award: Oral Epithelial Cells: Innate Immune "Gatekeeper" of HIV
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2003 - 2008

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2002 - 2012

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2002 - 2012

Award: Minnesota Craniofacial Research Training Program
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 2002 - 2009

Award: Innate Intraepithelial Defense against Oral Infection
Principal Investigator: Herzberg, Mark C
Sponsoring Organization: NIH NIDCR NATL INST OF DENTAL
Award Dates: 1997 - 2009
 

Periodontics, Residency
State University of New York