Mary Ann Jabra-Rizk, PhD
|Oncology and Diagnostic Sciences|
The research in our laboratory focuses on the characterization of virulence factors in the opportunistic fungal pathogen Candida albicans and on analyzing the various factors and conditions that play a role in the transition between colonization and infection. Specifically, we are interested in studying host-pathogen interactions, polymicrobial biofilms and drug tolerance.
Our laboratory developed a murine model of oral candidiasis to study the clinical implications of oral fungal-bacterial interactions in biofilms particularly in the immunocompromised hosts. We are currently pursuing development of novel therapeutic strategies targeting these complex polymicrobial infections. We are also using our mouse model to investigate the role of host oral innate immunity, specifically the salivary antimicrobial peptide histatin-5, in defense against colonization and infection by C. albicans. We recently demonstrated significant decrease in the salivary levels of this anti-candidal peptide in HIV-infected individuals, characterizing a defined mechanism behind the enhanced prevalence of oral candidiasis in this population. We are currently performing prospective clinical studies to monitor the decline in host innate immune defenses during the progression of HIV disease.
Our interest in exploiting the potent anti-candidal property of histatin-5 for potential application as a novel antifungal agent led to the recent development of a bioadhesive hydrogel-based delivery system for histatin-5. The formulation is currently being tested in the mouse model as well as in a rat model of Candida-associated denture stomatitis. The goal of these studies is to develop a pharmaceutically viable oral topical formulation for the prevention and/or treatment of oral infections in immunocompromised individuals.
Our laboratory is also interested in understanding the dynamics of biofilm formation by C. albicans as orchestrated by quorum sensing molecules and their role in development of drug resistance. We are specifically interested in a molecule with anti-microbial and anti-tumor properties. Since fungal and human cells are eukaryotic sharing similar metabolic pathways, our efforts have focused on identifying the mechanism of cytotoxicity of this molecule in C. albicans and human cancer cells. We are currently exploring the potential of this molecule as an anti-tumor agent using a xenograft mouse model of oral squamous carcinoma. In collaboration with the Dental School as the University of Amsterdam (ACTA), we are also investigating the role of the interaction between C. albicans and Streptococcus mutans on the development and progression of caries.
1. Mark A. Scheper, Mark E. Shirtliff, Timothy F. Meiller, Brian Peters and Mary Ann Jabra-Rizk. Farnesol a Fungal Quorum Sensing Molecule Triggers Apoptosis in Human Oral Squamous Carcinoma Cells. Neoplasia 2008: 10(9): 954-963. PMID: 18714396.
2. Sandra R. Torres, Alfredo Garzino-Demo, Ming Zhang, Valli Meeks, Timothy F. Meiller and Mary Ann Jabra-Rizk. Salivary Histatin-5 and Oral Fungal Colonization in HIV+ Individuals. Mycoses 2008: 52: 11-15. PMID: 18983435.
3. Timothy F. Meiller, Bernhard Hube, Lydia Schild, Mark E. Shirtliff, Mark A. Scheper, Robert Winkler, Amy Ton and Mary Ann Jabra-Rizk. Novel Immune Evasion Strategy of Candida albicans: Proteolytic Cleavage of a Salivary Antimicrobial Peptide. PLoS ONE 2009 4(4): e5039, 1-9. PMID: 19352427A.
4. Mark E. Shirtliff, Bastiaan P. Krom, Roelien A.M. Meijering, Brian M. Peters, Jingsong Zhu and Mary Ann Jabra-Rizk. Farnesol-Induced Apoptosis in Candida albicans. Antimicrobial Agents and Chemotherapy 2009 April 53(6): 2392-2401. PMID: 19364863.
5. Mark E. Shirtliff, Brian M. Peters and Mary Ann Jabra-Rizk. Cross-kingdom interactions: Candida albicans and Bacteria. FEMS Microbiology Letters 2009: 1-8. PMID: 19552706.
6. Brian M. Peters, Jingsong Zhu, Paul L. Fidel Jr, Mark A. Scheper, William Hackett, Sara El Shaye and Mary Ann Jabra-Rizk. Protection of the Oral Mucosa by Salivary Histatin-5 against Candida albicans in an Ex Vivo Murine Model of Oral Infection. FEMS Yeast Research 2010; 10(5): 597-604
7. Brian M. Peters, Mary Ann Jabra-Rizk, Jeff G. Leid, Jim W. Costerton and Mark E. Shirtliff. Microbial interactions and differential protein expression within Candida albicans-Staphylococcus aureus polymicrobial biofilms. FEMS Immunology and Medical Microbiology 2010; (59):494-503.
8. Brian M. Peters, Mark E. Shirtliff and Mary Ann Jabra-Rizk. Antimicrobial Peptides: Primeval molecules or novel drugs? PLoS Pathogens 2010: 6(10): e1001067).
9. Mary Ann Jabra-Rizk. Pathogenesis of polymicrobial biofilms. Open Mycology Journal 2011; (5)39-43.
10. Clinton C. Dawson, Chaidan Intapa and Mary Ann Jabra-Rizk. “Persisters”: Survival at the Cellular Level PLoS Pathogens 2011: 7(7): e1002121.
11. Jingsong Zhu, Bastiaan P. Krom, Dominique Sanglard, Chaidan Intapa, Clinton C. Dawson, Brian M. Peters, Mark E. Shirtliff and Mary Ann Jabra-Rizk. Farnesol-Induced Apoptosis in Candida albicans is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione. PLoS ONE 2011: 6(12): e28830.
12. Brian M Peters, Mary Ann Jabra-Rizk, Graeme A O’May, J. William Costerton and Mark E Shirtliff. Polymicrobial interactions in biofilms: impact on pathogenesis and human disease. Clinical Microbiology Reviews 2012: 25(1): 193-213.
13. Brian M Peters, Ekaterina Ovchinnikova, Lisa Marie Schlecht, Lois L. Hoyer, Henk J. Busscher, H.C. van der Mei, Bastiaan P Krom, Mary Ann Jabra-Rizk and Mark E Shirtliff. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p. Microbiology (August) 2012. PMID: 22918893.
14. Shariq A Khan, Paul L Fidel Jr, Awdah Al Thunayyan, Sharon Varlotta, Timothy F Meiller, Mary Ann Jabra-Rizk. Impaired histatin-5 level and salivary antimicrobial activity against C. albicans in HIV-infected individuals. J AIDS Clin Res 2013 4(2):1-6.
15. Khalid H. Metwalli, Shariq A. Khan, Bastiaan P. Krom, Mary Ann Jabra-Rizk. Streptococcus mutans, Candida albicans and the Human Mouth: A Sticky Situation. PLoS Pathogens 2013 9(10); e1003616.
16. Chaidan Intapa, John Basile, and Mary Ann Jabra-Rizk. Farnesol-induced apoptosis in oral squamous carcinoma cells is mediated by MRP1 extrusion and depletion of intracellular glutathione. PLoS ONE 2013 (in press).
EDUCATION AND TRAINING:
Ph.D Microbiology and Immunology