Project ID CM-HD2026_50

ThemeCM-HD

Co Supervisor 1A Dr Miguel Reis Ferreira Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Host-Microbiome InteractionsEmail

Co Supervisor 1B Prof Mike Curtis Faculty of Dentistry, Oral & Craniofacial Sciences, Centre for Host-Microbiome InteractionsEmail

Deciphering the role of intra-tumoural bacteria in the prognosis and treatment response in head and neck cancers: a translational study.

(a) This project aims to unlock how bacteria living within head and neck squamous cell carcinoma (HN-SCC) influence patient survival, with a special focus on a group of bacteria called Fusobacterium.

Our recent published research suggests that patients whose tumours contain more Fusobacterium may actually have better outcomes. However, only a small subset of patients has been studied so far, and we do not fully understand why this effect occurs in humans or whether other bacteria play a role.

The student will analyse large genetic datasets from hundreds of cancer patients in The Cancer Genome Atlas (TCGA) and Cancer Genomics England (CGE) HN-SCC cohorts, which will be filtered using advanced computational methods to derive bacterial communities living within cancers. They also provide data about the cancers themselves and their associated immunity. Using imputed metagenomics, we can also predict which molecules the microbiome produces.
Using the full TCGA cohort (500+ patients), the student will map intra-tumoural bacterial communities, explore how they interact with each other, the tumour, and immune cells living within it. They will also explore whether certain bacterial products, especially those known to kill HN-SCC in laboratory experiments conducted at the Reis Ferreira lab, are linked to better patient survival. Findings will be validated in the unique UK CGE dataset.

In tandem with our ongoing wet lab research, this project will provide critical information to develop novel prognostics and treatments for HN-SCC.

(b) Skills and Techniques Developed:
The student will gain experience in bioinformatics, data analysis, and cancer/microbiome research. They will learn to handle large-scale genetic data, interpret complex biological patterns, and work with clinical information. The project will also involve scientific communication and multidisciplinary collaboration.

(c) Aims:
The overarching aim is to understand how bacteria living within HN-SCC affect survival to improve patient care.

(d) Yearly Objectives:
Year 1: Learn core bioinformatics skills, process genetic data from cancer patients, and identify key bacteria linked to survival.

Year 2: Explore how groups of bacteria and their metabolic activities influence cancer outcomes, and investigate how bacteria interact with cancer-associated immunity.

Year 3: Validate findings, prepare results for publication.

Year 4: Complete analysis, write thesis, and present/publish findings.

(e) 3-Month Rotation Project:
To develop a robust foundation for the main project, the student will analyse a subset of already available cancer data (HN-SCC/colorectal/oesophageal cancers) to identify the most common bacteria in tumours and explore their links to patient outcomes while controlling for established confounding factors.

Representative Publications

1. Chander A, Iacovacci J, Pellon A, Kataria R, Grigoriadis A, Maher J, Sears C, Bachrach G, Urbano TG, Lei M, Petkar I, Kong A, Ng T, Orlandi E, Iacovelli NA, De Cecco L, Serafini MS, Moyes D, Rancati T, Ferreira MR. Fusobacterium is toxic for head and neck squamous cell carcinoma and its presence may determine a better prognosis. Cancer Commun (Lond). 2024 Aug;44(8):879-883. doi: 10.1002/cac2.12588. Epub 2024 Jul 6. PMID: 38970403; PMCID: PMC11337922.;
2. Reis Ferreira M, Pasto A, Ng T, Patel V, Guerrero Urbano T, Sears C, Wade WG. The microbiota and radiotherapy for head and neck cancer: What should clinical oncologists know? Cancer Treat Rev. 2022 Sep;109:102442. doi: 10.1016/j.ctrv.2022.102442. Epub 2022 Aug 1. PMID: 35932549.;
3. Reis Ferreira M, Andreyev HJN, Mohammed K, Truelove L, Gowan SM, Li J, Gulliford SL, Marchesi JR, Dearnaley DP. Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy. Clin Cancer Res. 2019 Nov 1;25(21):6487-6500. doi: 10.1158/1078-0432.CCR-19-0960. Epub 2019 Jul 25. PMID: 31345839.

1. Joseph S, Carda-Diéguez M, Aduse-Opoku J, Alsam A, Mira A, Curtis MA. The Murine Oral Metatranscriptome Reveals Microbial and Host Signatures of Periodontal Disease. J Dent Res. 2023 May;102(5):565-573. doi: 10.1177/00220345221149675. Epub 2023 Mar 8. PMID: 36883648; PMCID: PMC10152569.;
2. Aduse-Opoku J, Joseph S, Devine DA, Marsh PD, Curtis MA. Molecular basis for avirulence of spontaneous variants of Porphyromonas gingivalis: Genomic analysis of strains W50, BE1 and BR1. Mol Oral Microbiol. 2022 Jun;37(3):122-132. doi: 10.1111/omi.12373. Epub 2022 Jun 2. PMID: 35622827; PMCID: PMC9328147.;
3. Joseph S, Aduse-Opoku J, Hashim A, Hanski E, Streich R, Knowles SCL, Pedersen AB, Wade WG, Curtis MA. A 16S rRNA Gene and Draft Genome Database for the Murine Oral Bacterial Community. mSystems. 2021 Feb 9;6(1):e01222-20. doi: 10.1128/mSystems.01222-20. PMID: 33563782; PMCID: PMC7883545.