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Professor Gary Moran

Professor in Microbiology (Dental Science)
      
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Professor Gary Moran

Professor in Microbiology (Dental Science)

 gmoran@tcd.ie

 3531 6127245


I run the Oral Microbiome research group in the School of Dental Science. My research focuses on the pathogenicity of oral microorganisms, specifically the fungal pathogen Candida albicans and the oral bacterium Fusobacterium nucleatum. Our research involves a combination of molecular genetics, genomics and transcriptomics. We also carry out 16S profiling of the oral microbiome to better understand oral disease. Our research is carried out in the Microbiology laboratory at the Dublin Dental University Hospital, which is on the campus of Trinity College Dublin.
  16s Profiling   antifungal drug resistance   CANDIDA ALBICANS   comparative genomics   fungal morphogenesis   Fusobacterium nucleatum   Genomes, Genomics   in vitro models of infection   microbiome   Molecular Biology   Periodontal disease   Porphyromonas gingivalis   Tissue Culture   transcriptomics   virulence factors
Project Title
 The role in virulence and drug target potential of the Candida albicans telomeric TLO gene family
From
2020
To
Present
Summary
The genome of the fungal pathogen Candida albicans contains a family of ~14 telomeric TLO genes encoding putative transcription factors. The closely related non-pathogenic species C. dubliniensis contains only two orthologous genes, suggesting that the increased gene number in C. albicans may contribute to the increased virulence of this species. Using a combination of mutant construction, transcript profiling and ChIP-Chip analysis, this study aims to determine the role of these gene in the biology and virulence of Candida species.
Funding Agency
Science Foundation Ireland
Programme
Frontiers for the Future
Project Type
Basic Research
Project Title
 The role of Fusobacterium nucleatum and Candida albicans interkingdom interactions in promoting OSCC
From
01/01/24
To
31/12/25
Summary
Oral squamous cell carcinoma (OSCC) exerts a significant clinical and financial burden worldwide. Recently, there has been increasing interest in the role of the microbiome in OSCC. Among microbial species that have frequently been identified in association with OSCC and demonstrated to promote oral carcinogenesis, both in vitro and in animal models, include the bacterium Fusobacterium nucleatum and the fungus Candida albicans. The two species have been demonstrated to interact via co-aggregation; however, whether such interkingdom interaction can promote oral carcinogenesis has never been explored The current proposal builds on our previous studies investigating the microbiome associated with OSCC and oral leukoplakia in clinical samples, and assessing the effects of oral bacteria against oral epithelial cell lines in vitro. The proposed studies will investigate for the first time the potentially synergistic interaction between C. albicans and F. nucleatum in malignant progression, which we hypothesize is facilitated by their coaggregation. Based on our preliminary data, we also hypothesize that the two species mediate part of their oncogenic properties through upregulation of INHBA, a proposed oncogene acting through the TGF-ß pathway. To address these hypotheses, we propose to assess synergistic effects of C. albicans and F. nucleatum on normal, dysplastic, and neoplastic oral epithelium in vitro (Aim 1), and to study the carcinogenicity of C. albicans and F. nucleatum co-carriage in 4-nitroquinoline-1-oxide-induced OSCC mouse model (Aim 2). Combinations of wild-type, aggregation +ve strains and mutant, aggregation-deficient strains of the two species will be used in the two aims to assess the role of co-aggregation in promoting synergistic carcinogenicity. The involvement of INHBA upregulation in this synergy will be investigated by mechanistic gene knockdown experiments. The project will employ a range of technologies including cellular and biochemical assays, metatranscriptomics, histopathology, immunohistochemistry, flow cytometry, q-PCR, fluorescent in-situ hybridization and 16S sequencing to investigate the effect of treating the cell lines and mice with the test species. This innovative, exploratory study leverages the complementary expertise of the research team to provide a first insight into the potential role of interkingdom microbial interactions in OSCC and shed light on novel mechanisms by which C. albicans and F. nucleatum may contribute to oral carcinogenesis
Funding Agency
National Institutes of Health (NIH)
Programme
R21
Project Type
R&D
Person Months
1
Project Title
 Analysis of the oral metagenome for markers of malignant transformation of oral leukoplakia
From
01/10/2019
To
30/09/2024
Summary
Oral squamous cell carcinoma (OSCC) accounts for 90% of oral cancers. According to the National Cancer Registry, the rate of OSCC in Ireland is increasing annually by 3.3%. OSCCs can arise de novo or from preneoplasis such as Oral Leukoplakia (OLK). Risks factors for OLK include smoking and alcohol consumption, however the mechanisms by which OLK progresses to OSCC are poorly understood and it is difficult to predict which OLKs will resolve or progress. The degree of dysplasia on biopsy is the best indicator of progression, with severe dysplasia being associated with greater risk relative to mild or moderate dysplasia. Recently, oral bacteria such as Fusobacterium nucleatum have been identified as potential drivers of malignant progression in the GI tract. Our recently published preliminary data examining the microbiome of OLK has shown that OLK lesions are colonised with a greater abundance of Fusobacteria, Campylobacter species and Candida albicans compared to healthy mucosa from the same patient. Our hypothesis is that changes in the composition of the mucosal microbiome are a driver of the malignant transformation of oral leukoplakia (OLK) to oral squamous cell carcinoma (OSCC). Characterisation of these microbiome changes will allow us to identify the organisms associated with severe dysplasia and therefore develop tests to identify the patients at greatest risk of malignant progression. In this study we will carry out a comprehensive comparison of the OLK microbiome compared to the healthy mucosal microbiome by Illumina sequence analysis in a large cohort of patients (n=235) to determine whether colonisation of OLK with certain microorganisms is significantly associated with severe dysplasia. These data will indicate whether routine microbiome profiling could be useful as a tool to predict the risk of malignant progression and whether topical antibiotic therapy is warranted to reduce the risk of OSCC.
Funding Agency
Health Research Board
Programme
Investigator Led Projects
Project Type
Health Research
Project Title
 The Oral Microbiome in Disease
From
01/09/2014
To
Present
Summary
The oral micro biome constitutes several hundred species of bacteria and fungi. Their role in oral and systemic health is poorly understood. This study will use 16s and 18s sequencing to identify populations associated with malignant lesions in the oral cavity and marker organisms for diseases of the bowel (colitis and Crohn's)
Funding Agency
Libyan People's Bureau
Programme
PhD Scholarship
Project Type
Health Research
Project Title
 The role of Tor kinase in filamentation in Candida albicans and Candida dubliniensis
From
2011
To
2015
Summary
Our recent studies have highlighted the role of nutrients and the nutrient sensing kinase Tor1 in regulating filamentation and virulence in the fungal pathogen C. dubliniensis. In this study we will examine the role of mutations in the Tor kinase pathway that lead to Tor hyperactivity. It is our hypothesis that Tor hyperactive strains of C. albicans will resemble the less virulent pathogen C. dubliniensis. These data will indicate whether Tor agonists have potential as antifungal agents.
Funding Agency
Science Foundation Ireland
Programme
Research Frontiers Programme

Page 1 of 4
Details Date
Member of the Irish Expert body on Fluorides and Health 2020-Present
Irish Division Committee, Microbiology Society UK 2021-2022
President of the Irish Fungal Society 2015-2019
Meetings Secretary of the British Society of Medical Mycology 2006-2009
Editor for Scientific Reports (Nature Publishing group) 2017-Present
Topic Editor for Frontiers in Microbiology 2017-2021
Grant reviewer for MRC UK, Wellcome Trust, NSF USA, and H2020 Marie Curie Fellowship programme, among others. 2010-Present
Details Date From Date To
British Society for Medical Mycology 1994 Present
Internation Association of Dental Research (IADR) 1998 Present
American Society for Microbiology 2000 Present
Society for General Microbiology 2007 Present
Dublin Academy of Pathogenomics and Infection Biology 2010 Present
Irish Fungal Society (IFS) Present 2010
Galvin S, Honari B, Anishchuk S, Healy CM, Moran GP., Oral Leukoplakia Microbiome Predicts the Degree of Dysplasia and is Shaped by Smoking and Tooth Loss., Oral diseases, 2025, Journal Article, PUBLISHED  DOI
Crowley C, Selvaraj A, Hariharan A, Healy CM, Moran GP., Fusobacterium nucleatum subsp. polymorphum recovered from malignant and potentially malignant oral disease exhibit heterogeneity in adhesion phenotypes and adhesin gene copy number, shaped by inter-subspecies horizontal gene transfer and recombination-derived mosaicism., Microbial genomics, 10, (3), 2024, Journal Article, PUBLISHED  DOI
O'Connor-Moneley J, Fletcher J, Bean C, Parker J, Kelly SL, Moran GP, Sullivan DJ., Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance., PloS one, 19, (8), 2024, pe0308665 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Selvaraj A, McManus G, Healy CM, Moran GP, Fusobacterium nucleatum induces invasive growth and angiogenic responses in malignant oral keratinocytes that are cell line- and bacterial strain-specific., Frontiers in cellular and infection microbiology, 2024, Journal Article, PUBLISHED  DOI
O'Connor M, Harrison G, Lenahan D, Moran GP., A dentifrice containing salivary enzymes and xylitol exhibits superior antimicrobial activity in vitro against adherent Streptococcus mutans compared to a chlorhexidine dentifrice., Letters in applied microbiology, 76, (2), 2023, povad026 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Moran GP, Zgaga L, Daly B, Harding M, Montgomery T., Does fluoride exposure impact on the human microbiome?, Toxicology letters, 2023, pS0378-4274(23)00098-X , Journal Article, PUBLISHED  TARA - Full Text  DOI
O'Connor-Moneley J, Alaalm L, Moran GP, Sullivan DJ., The role of the Mediator complex in fungal pathogenesis and response to antifungal agents., Essays in biochemistry, 2023, pEBC20220238 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Galvin S, Moran GP, Healy CM., Influence of site and smoking on malignant transformation in the oral cavity: Is the microbiome the missing link?, Front Oral Health, 4, 2023, p1166037 , Journal Article, PUBLISHED  DOI
Winning L, Moran G, McClory M, El Karim I, Lundy FT, Patterson CC, Linden D, Cullen KM, Kee F, Linden GJ., Subgingival microbial diversity and respiratory decline: A cross-sectional study., Journal of Clinical Periodontology, 50, (7), 2023, p921 - 931, Journal Article, PUBLISHED  DOI
Galvin, Sheila, Anishchuk, Sviatlana, Healy, Claire M., Moran, Gary P., Smoking, tooth loss and oral hygiene practices have significant and site-specific impacts on the microbiome of oral mucosal surfaces: a cross-sectional study, Journal of Oral Microbiology, 15, (1), 2023, p2263971 , Journal Article, PUBLISHED  DOI
  

Page 1 of 10
GARY P. MORAN, WHY CANDIDA ALBICANS FILAMENTS BETTER THAN ITS BUDDING COUSIN, EUKARYOTIC CELL, 9, (9), 2010, p1299 - 1299, Notes: [Spotlight feature on O'Connor et al. 2010, an "Article of Significant Interest Selected from This Issue by the Editors."], Journal Article, PUBLISHED
GARY P. MORAN, MARY ANN JABRA-RIZK, 8TH ASM CONFERENCE ON CANDIDA AND CANDIDIASIS: MOLECULAR TOOLS, MYCOPATHOLOGIA, 162, 2006, p17 - 24, Journal Article, PUBLISHED

  


Award Date
Fellow of TCD 22/04/2024
Irish Division of International Association of Dental Research (IADR) Elida Gibbs Award 1998
EMBO Short-term Fellowship 1997
F.S. Stewart prize (Awarded by Dept. of Microbiology, TCD, for highest grade in moderatorship exam) 1994
Since embarking on my PhD studies in 1994, I have been investigating the molecular biology of pathogenic oral microorganisms. My goal is to use the tools of molecular biology and genomics to understand the evolution of pathogenicity in oral microorganisms. Since becoming Associate Professor at the School of Dental Science at Trinity College Dublin, my research interests have expanded to examine how complex communities of oral microorganisms (i.e. microbiomes) evolve in health and disease. I have an interest in how the oral microbiome influences the overall health of the GI tract and in identifying novel microbial-induced disease mechanisms. I am currently collaborating with Crumlin Children's hospital to investigate whether Crohn's disease induces changes in the oral microbiome and to determine whether this can be used to diagnose IBD. I am also PI on a HRB funded study to investigate the premalignant condition oral leukoplakia (OLK) to understand if colonization of these lesions with a dysbiotic microbiome could act as a driver of malignant progression. Linked with this I have PhD students carrying out mechanistic studies investigating how oral bacteria, specifically Fusobacteria, interact with oral cells and how these bacteria could induce malignant changes in host epithelial cells. In addition to my research on the oral microbiome, my work on virulence and drug resistance Candida species has resulted in numerous highly cited publications. Very soon after the publication of the C. albicans genome sequence in the early 2000's, my research focused on exploiting this sequence information to identify the genes that make C. albicans the most virulent of the Candida species. In one of the first microarray studies to be published on Candida species, I carried out comparative genomic hybridizations between C. dubliniensis and C. albicans on glass slide arrays that identified many unique genes in C. albicans such as the virulence factors SAP6 and HYR1, and also identified a C. albicans-specific family of genes known as the TLO family of genes, due to their telomeric location. In collaboration with Derek Sullivan, we used these data to successfully lobby the Sanger Centre in Cambridge UK to generate a whole genome sequence for C. dubliniensis at a time when genome sequencing was a major under-taking. These data were published in Genome Research and highlight many disparities in gene family content between C. albicans and C. dubliniensis. I was the first molecular biologist to develop tools to study the pathogenicity of Candida dubliniensis that have facilitated a new field of comparative virulence in Candida species. I am currently funded by SFI to investigate the function of the novel TLO gene family in C. albicans using CRISPR-Cas9 mutagenesis to create TLO gene mutants in order to determine their role in the evolution of virulence in C. albicans.