Sequeira Lab

Regeneration and Cancer Systems Biology

We study how the oral mucosa achieves its remarkable scarless healing and how immune balance and tissue regeneration are disrupted in disease and cancer, aiming to bring these lessons to skin repair and therapy.

At the Sequeira Lab, we’re fascinated by the body’s ability to heal.

The oral mucosa, unlike skin, can repair quickly and in a scarless fashion, and we want to understand the secrets behind this scarless healing.

Our work looks at what happens when this perfect balance is disrupted in conditions like epidermolysis bullosa and oral cancer.

The immune system plays a key role in both wound healing and cancer and we are interested in understanding how it supports healthy repair and shapes immune tolerance in the mouth and skin.

By combining cutting‑edge tools in single‑cell and spatial genomics, proteomics, and advanced tissue models, we map how different cells talk to each other during healing and disease.

Guided by a strong team science ethos, we collaborate closely with partner research groups, clinical teams, and bioinformaticians to lead truly integrated projects.

Ultimately, our goal is to turn these discoveries into new ways to improve wound healing, prevent scarring, and guide more personalised approaches to cancer therapy.

 

PROJECTS

 


Project description

The oral mucosa is a remarkable tissue that heals faster than skin and does so without scarring, making it a powerful model for uncovering the cellular and molecular mechanisms behind regenerative repair. We are particularly interested in how fibroblasts and immune cells coordinate this process. We combine single-cell and spatial omics with live-imaging tools to understand the cellular and molecular mechanisms that underlie this unique form of wound healing, with the broader goal of applying these lessons to improve skin repair. By uncovering these differences, we hope to identify new strategies to enhance wound healing and reduce scarring.

Principal Investigator: Inês Sequeira

Funded under: British Skin Foundation

Grant category: Research Grants

 


Project description

This project contributes to the Human Cell Atlas by building a detailed cellular map of healthy human oral and craniofacial tissues. The oral cavity contains multiple highly specialised niches, including mucosa, tongue, salivary glands, periodontium, palate, and tonsils, each with distinct cellular compositions and tissue functions.

Our team uses single-cell and spatial omics to define the shared and tissue-specific cell populations that support oral health and respond to injury, inflammation, and disease. The atlas is being developed as an openly accessible reference resource to support future studies in precision diagnostics, biomarker discovery, and oral and craniofacial disease biology.

 

Principal Investigator: Inês Sequeira

Funded under: Chan Zuckerberg Initiative (CZI) 


Project description

Epidermolysis bullosa (EB) is a severe genetic disease characterised by skin fragility, chronic wounds, inflammation, and scarring, and it can also affect the oral mucosa. In this project, we are comparing healthy and EB-affected oral and skin tissues to understand why scarless healing is lost and which cellular programs drive fibrosis and persistent inflammation.

Our long-term goal is to uncover mechanisms that can support more personalised diagnostics and therapies for chronic wounds and scarring disorders, including EB.

Principal Investigator: Inês Sequeira

Funded under: DEBRA UK.

DOI: DEBRA UK (https://www.debra.org.uk/eb-research/eb-research-projects/deb-cancer-and-mouth-wound-healing/)


Project description

Our goal is to understand how immune tolerance is maintained in the skin and oral mucosa, and how disruptions in this system can lead to inflammation and cancer. Building on our work on Keratin 76, we are investigating how keratin expression in thymic epithelial cells influences T cell education. We aim to explain how breakdowns in immune tolerance contribute to chronic inflammation, altered wound healing, and increased cancer risk, with the broader goal of informing precision immunotherapies.

Principal Investigator: Inês Sequeira

Funded under: UK Medical Research Council; Barts Charity.


Project description

Oral cancers are highly heterogeneous, and our previous work showed that mutational subclones, immune composition, and stromal context all shape tumour behaviour and metastatic potential.

We are combining whole-exome sequencing and spatial omics to map tumour subclones and their surrounding immune and stromal populations in both primary and metastatic disease. By linking genetic evolution with tissue architecture, this work aims to identify biomarkers of invasion, improve understanding of tumour ecology, and support the development of personalised diagnostic and therapeutic strategies.

Principal Investigator: Inês Sequeira

Funded under: Barts Charity; British Council

 

TEAM

 


Group Leader

Inês Sequeira is Principal Investigator and Vice-Director for Research at NIMSB.

Inês obtained her Biology degree from the University of Lisbon and Université Libre de Bruxelles, where she specialised in genetics and developmental biology. She completed her PhD at Institut Pasteur, in Paris, working as part of a multidisciplinary team to investigate stem cell heterogeneity and behaviour in the hair follicle, using lineage tracing, clonal analysis, imaging and mathematical modelling.

In 2014, Inês joined the lab of Prof Fiona Watt at King’s College London for her postdoctoral training on epithelial stem cells and cancer biology. During her postdoc, she discovered a novel immunoregulatory role for Keratin 76 in tumour development and led work on the genetic and cellular heterogeneity of oral squamous cell carcinoma. By linking whole-exome sequencing data with tumour location, clonal organisation, and immune infiltration, her research helped reveal the dynamics of oral cancer formation and opened new avenues for early diagnosis, and disease monitoring.

Following her postdoctoral training, Dr Sequeira led a research group at L’Oréal R&I, where she investigated skin ageing and regeneration.

In 2020, Inês joined the Institute of Dentistry at Queen Mary University of London as Associate Professor (Reader) and Deputy Director of Research.

Dr Sequeira’s lab focuses on the molecular and cellular mechanisms underlying oral cancer formation and the regenerative capacity of the oral mucosa, a tissue known for its rapid, scarless healing compared with skin. Her team combines experimental and computational approaches, including advanced imaging, transcriptomics, and mathematical modelling, to map cellular interactions and uncover the intrinsic and extrinsic signals that shape oral wound healing and tumour development.

Committed to collaborative science, she co-founded the London Stem Cell Network  and the SpatiaLondon network (network on Spatial Biology), and currently coordinates the Oral and Craniofacial Bionetwork of the Human Cell Atlas

 

                               

 

 

 


PhD Fellow 

Inês Saldanha has an academic background in Biology and Biomedical Research. She has developed research experience across several areas of the life sciences, including biochemistry, cancer biology, and immunology. More specifically, she has been involved in projects related to protein-protein interactions in xenobiotic metabolism pathways, intercellular communication and biomarker discovery in cancer, and has also explored innate immune responses to AAV-based gene delivery using 3D cell culture models. She is currently pursuing a PhD in Molecular Biosciences at ITQB NOVA, funded by a NIMSB fellowship in the Sequeira Lab, where she focuses on epithelial immunity and tumour development. Inês is also actively engaged in science communication through Pint of Science, where she is part of the national communication team.

                

 

 

 

 


Postdoctoral Research Associate

Diana Pereira is a Postdoctoral Researcher with a background in biochemistry, biotechnology, and a PhD in epithelial biology from Queen Mary University of London. Her research focuses on understanding tissue homeostasis and repair through the lens of multiomic technologies. Diana has extensive experience in single-cell RNA sequencing and spatial omics, which she use to dissect cellular heterogeneity and map cell–cell interactions in complex tissues. She is currently a postdoctoral researcher in Sequeira’s lab at Queen Mary University of London and her work integrates computational and experimental approaches, including organoid models, in vivo and in vitro systems and imaging.

 

         

 


Postdoctoral Research Associate

Mara Gelmetti completed her PhD in Immunology in May 2025 at Queen Mary University London and she is now working as a Postdoctoral Research Associate in the Sequeira lab at Queen Mary University of London. Her research focuses on the role of the thymus on central tolerance and more specifically on how keratins found in the thymus are crucial to prevent skin inflammatory diseases. Her work combines bioinformatics approaches and phenotypic characterisation with genetic models to investigate the functional function of thymic keratins in T cell development. Previously to her PhD, she worked as a research assistant at King’s College London in the Department of Infectious Diseases, an industrial placement intern at Kymab Ltd. (now Sanofi) and completed my BSc in Pharmacology at the University of Bath.

 

 

 

 

 

SELECTED PUBLICATIONS

 

Matuck BF, Huynh KLA, Pereira D, Easter QT, Zhang X, Kunz M, Kumar N, Pratapa A, Rupp BT, Ghodke A, Predeus AV, Fernandes A, Szabó L, Hartmann S, Harnischfeger N, Khavandgar Z, Beach M, Perez P, Nilges B, Moreno MM, Ko KI, Singh R, Tata PR, Teichmann SA, Kimple A., Pringle S, Kretzschmar K, Warner BM, Sequeira I*#, Liu J* & Byrd KM*#. An integrated single-cell and spatial proteotranscriptomics atlas of fibroblast-driven immunoregulation within the human adult oral cavity. Cell Press Blue (2026) | #Senior authors, *Corresponding authors  (doi:10.1016/j.cpblue.2026.100007)

 

Tissot N, Genty G, Santoprete R, Baltenneck F, Thibaut S, Michelet JF, Sequeira I*, Bornschlögl T*Mapping cell dynamics in human follicles reveals mechanisms of hair growth. Nature Communications (2025) (doi.org/10.1038/s41467-025-65143-x) *Corresponding author

 

Lim KHJ, Tippu Z, Corrie PG, Hubank M, Larkin J, Lawley TD, Stares M, Stewart GD, Strange A, Symeonides SN, Szabados B, Turner NC, Waddell T, Zelenay S, Salto-Tellez M, Dive C, Turajlic S; MANIFEST consortium: Sequeira I et al.  MANIFEST: Multiomic Platform for Cancer Immunotherapy. Cancer Discov (2025) (doi: 10.1158/2159-8290.CD-25-0099)

 

Sequeira I, Rashid M, Tomas I, Williams M, Graham T, Adams D, Vigilante A, Watt FM. The genomic landscape and clonal selection of carcinogen-induced mouse oral squamous cell carcinoma. Nature Communications (2020) (doi:10.1038/s41467-020-19401-9)

 

Sequeira I, Neves JF, Carrero D, Peng Q, Palasz N, Liakath-Ali K, Morgan P, Graham L, Lombardi G, Watt FM. Immunomodulatory role of Keratin 76 in oral and gastric cancer. Nature Communications (2018). (doi:10.1038/s41467-018-05872-4)

 

Liakath-Ali K, Mills EW, Sequeira I, Lichtenberger BM, Pisco AO, Sipilä KH, Mishra A, Yoshikawa H, Chih-Chien Wu C, Ly T, Lamond A, Adham IM, Green R, Watt FM. An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature (2018) (doi: 10.1038/s41586-018-0032-3)