Microbiome in Health & Disease Translational Laboratory

The Microbiome in Health and Disease Translational Laboratory is an interdisciplinary and highly collaborative team of clinical microbiologists, computational biologists, nutritionists, immunologists, and gastroenterologists.

Our lab is dedicated to leveraging the potential of the microbiome to revolutionize the field of colorectal cancer (CRC) research. Our mission is to develop innovative diagnostic tools and microbiome-based biotherapeutics to intercept, prevent, and treat CRC.

Our research focuses on three key areas:

Biomarker Discovery: We aim to identify and validate novel gut microbiome biomarkers for risk assessment and early CRC diagnosis using precision microbiome profiling and machine learning technology. By analyzing the gut microbiota in individuals at different stages of CRC, we aim to enhance screening methods and enable early intervention.

Host-Microbiome Interactions: We study the role of microbial metabolites in shaping host immune responses in CRC. Through metabolomic profiling and culturomics, we aim to uncover the specific microbial metabolites linked to distinct immune responses in CRC. This knowledge will deepen our understanding of the microbiome-immune system crosstalk and facilitate the development of novel biotherapeutics.

Microbiome-based therapeutics: Another important focus of our lab is the development of microbiota consortia comprising commensal immune-stimulating bacteria. By harnessing the power of these beneficial microbes, we aim to modulate the host immune system in a favourable manner, potentially mitigating the risk of CRC development or aiding in treatment strategies. This research avenue holds promise for the development of novel probiotics or microbial-based therapies that can be tailored to specific individuals or subgroups at risk.

Through an ambitious and multidisciplinary approach that combines cutting-edge techniques in genomics, metabolomics, and immunology, our lab strives to unravel the complex interplay between the microbiome and CRC. By elucidating the underlying mechanisms, we aim to translate our findings into tangible clinical applications that will have a significant impact on cancer prevention, diagnosis, and treatment.

Team

Areas

• Identification of novel gut microbiome biomarkers for risk assessment and early diagnosis of Colorectal Cancer
• Unravelling novel microbial metabolites associated with distinct host immune responses in Colorectal Cancer
• Development of microbiome-based therapies for the treatment of Colorectal Cancer

Ongoing Projects

2023-2029 Improving Colorectal Cancer Early Screening in Portugal: Identification and Validation of Gut Microbiome and Methylation Biomarkers. Funding Agency: European Commission.

2023-2028 MISSION – The Power of Microbiota to Modulate the Immune Response in Colorectal Cancer. Funding Agency: Fundação para a Ciência e a Tecnologia.

Awards

2023-2028 Fundação para a Ciência e a Tecnologia (FCT) Scientific Employment Stimulus – Auxiliary Researcher

2021 Trainee Award from the American Association of Immunologists (AAI)

2021 Justice, Equity, Diversity and Inclusion Award from the Life Sciences Editors Foundation

2021 Research Grant from the Irish Higher Education Authority

2020 Erasmus+ Training Grant

2017 Research Grant from the Portuguese Association of Researchers and Students in the UK (PARSUK) Xperience 2017, Fundação Calouste Gulbenkian

2017 Postdoctoral Fellowship, H2020 Marie Sklodowska-Curie Actions Individual Fellowship

Selected Publications

Tosti E, Almeida AS, Tran TT, Silba MB, Broin PO, Dubin R, Chen K, Beck A, McLellan A, Vilar-Sanchez E, Golden A, O’Toole PW, Edelmann W (2022). Loss of MMR and TgfβII increases the susceptibility to microbiota-dependent inflammation-associated cancer. Cellular and Molecular Gastroenterology and Hepatology 14:693–717, doi:10.1016/j.jcmgh.2022.05.010

Bird BH, Nally K, Ronan K, Clarke G, Amu S, Almeida AS, Flavin R, Finn S (2022). Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise. Diagnostics 12:124. doi:10.3390/diagnostics12010124

Almeida AS, Tran TT, Ghosh TS, Ribière C, Foley C, Azevedo LA, Pellanda P, Frei W, Hueston CM, Kumar R, Flemer B, Sequeira I, O’Riordain M, Shanahan F, O’Toole PW (2021). Fiber-associated Lachnospiraceae reduce colon tumorigenesis by modulation of the tumour-immune microenvironment. bioRxiv doi:10.1101/2021.02.24.432654

Almeida AS, Fein MR, Egeblad M (2021). Multi-color flow cytometry for comprehensive analysis of the tumor immune infiltrate in a murine model of breast cancer. Bio-protocol vol. 11, doi: 10.21769/bioprotoc.4012

Sun L, Almeida AS*, Kees T*, Liu B, He XY, Ng D, Spector D, McNeish IA, Gimotty P, Adams S, Egeblad M (2021). Activation of a collaborative innate-adaptive immune response suppresses metastatic breast and ovarian cancer in mice. Cancer Cell 39, 1361-1374.e9

Fein MR*, He XY*, Almeida AS, Bruzas E, Pommier A, Eberhadt A, Fearon DT, Wilkinson JE, dos Santos CO, Egeblad M (2020). Cancer cell CCR2 orchestrates suppression of the adaptive immune response. Journal of Experimental Medicine 217 (10) e20181551

Öhlund D*, Handly-Santana A*, Biffi G*, Elyada E*, Almeida AS, Ponz-Sarvise M, Corbo V, Oni TE, Hearn SA, Jung Lee E, Chio C, Hwang C-I, Tiriac H, Baker LA, Engle DD, Feig C, Kultti A, Egeblad M, Fearon DT, Crawford JM, Park Y, Tuveson DA (2017). Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. Journal of Experimental Medicine

Perurena N, Zandueta C, Martínez-Canarias S, Moreno H, Vicent S, Almeida AS, Guruceaga E, Gomis RR, Santisteban M, Egeblad M, Hermida J, Lecanda F (2017). EPCR promotes breast cancer progression by altering SPOCK1-mediated 3D growth. Journal of Hematology & Oncology 10:23

Park J*, Wysocki RW*, Amoozgar Z*, Maiorino L*, Fein M, Jorns J, Schott AF, Kinugasa-Katayama Y, Lee Y, Won NH, Nakasone ES, Hearn SA, Kuettner V, Qiu J, Almeida AS, Perurena N, Kessenbrock K, Goldberg M, Egeblad M (2016). Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Science Translational Medicine 8, 361ra138

Fevre C*, Almeida AS*, Taront S, Pedron T, Huerre M, Prevost MC, Kieusseian A, Cumano A, Brisse S, Sansonetti PJ, Tournebize R (2013). A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes. EMBO Molecular Medicine 5(4): 516-530

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