Profile
Dr Inês Sequeira joined the Institute of Dentistry at Queen Mary University of London, in 2020 as a Lecturer. She has been studying stem cell and cancer biology for the past 18 years. Inês obtained her Biology degree at Lisbon University and Université Libre de Bruxelles and moved to Institut Pasteur in Paris to complete her doctoral studies. During her PhD, she worked with a multidisciplinary team to investigate stem cell heterogeneity and behaviour in the hair follicle using clonal analysis, 3D imaging and mathematical modelling, and establishing a novel model to describe stem cell behaviour in the niche during hair regeneration. In 2014, Inês moved to London and joined the laboratory of Prof Fiona Watt, one of the world-leading labs in skin and stem cell biology, at the Centre for Stem Cells & Regenerative Medicine (King’s College London) for her postdoctoral training on cancer biology. There, she developed her line of research using a mouse model for oral cancer (OSCC), establishing methodologies that were entirely new to the lab. During her postdoc, she uncovered a novel immunoregulatory role for Keratin 76 during tumour development. Furthermore, she focused in understanding the genetic and cellular heterogeneity in OSCC, correlating the genetic changes identified by whole exome sequencing with their location, clonal organisation and immune infiltrate changes of individual tumours in order to determine the dynamics of OSCC formation. This analysis opens new avenues to the development of new biomarker testing for early stage mutations, improving early diagnosis and monitoring of oral cancer.
Dr Sequeira’s lab at QMUL is particularly interested in dissecting the molecular and cellular mechanisms involved in oral cancer formation and in understanding the regenerative potential of the oral mucosa, a tissue with rapid and scarless healing when compared to skin. Inês and her team combine experimental and theoretical approaches including cutting-edge imaging with computational modelling to map the cellular interactions, and transcriptomics to uncover intrinsic and extrinsic signals during oral wound healing and tumour formation.
Dr Sequeira is also involved in the Barts Centre for Squamous Cancer which is a cross-institute collaborative centre at QMUL, bringing together research groups with diverse expertise from across the School of Medicine and Dentistry to tackle the problem of squamous cancer and drive clinical innovation.
Furthermore, to promote collaborative science, she co-founded the London Stem Cell Network (https://lscn.co.uk/) and currently coordinates the Oral and Craniofacial Bionetwork of the Human Cell Atlas (https://www.humancellatlas.org/biological-networks/).
Personal Webpage: www.sequeira.science
Linkedin: https://www.linkedin.com/in/inesequeira
ResearchGate: https://www.researchgate.net/profile/Ines_Sequeira
Centre: Oral Immunobiology and Regenerative Medicine
Research
Research Interests:
Dr Sequeira’s lab is particularly interested in dissecting the molecular and cellular mechanisms involved in oral cancer formation and in understanding the outstanding regenerative potential of the oral mucosa, a tissue with rapid and scarless healing when compared to skin. Our aim is to combine experimental and theoretical approaches including advanced single cell and spatial multi-omics, multiplex imaging, 2D and 3D organoid technology, 3D live-imaging to unravel fundamental mechanisms underlying oral wound healing and tumour formation.
Ongoing research projects:
1. Creating the Oral Cell Atlas.
We just completed a molecular (single cell RNA sequencing) and spatial cell atlas of human oral cavity as part of the Oral and Craniofacial Human Cell Atlas, where we defined the heterogeneity of 11 different oral niches. In parallel, we have also created the first Oral Cell Atlas for the mouse tissues, during development, neonatal and adult stages. (Caetano et al, J Dent Research, 2022; Pereira et al, JID, 2023; Huang et al, Nature Medicine, 2021)
If interested in collaborating with the Oral Human Cell Atlas, get in touch (https://www.humancellatlas.org/biological-networks/)
2. The scarless wound healing of the oral mucosa.
Wound healing is a complex biological process that requires overlapping phases of haemostasis, inflammation, cell proliferation and remodelling of the dermis where the fibroblasts reside.
While in skin wound healing results in scar formation, the oral mucosa holds a unique and fascinating property as it rarely scars. What drives scarless healing in healthy oral mucosa? How can we apply this remarkable scarless potential to improve skin wound healing? Using the expertise and knowledge gained from the cell atlases generated, together with in vitro and in vivo testing, we uncover the molecular signatures of scarless and rapid wound healing that can be targeted to reduce skin fibrosis and accelerate healing. This research has broad translational applications: the identification of the microenvironment signatures in scarless tissues offer an exciting strategy to accelerate wound healing in patients with chronic wounds, like in Epidermolysis bullosa, or after tumour resection surgical treatment, improving patients’ quality of life.
(Pereira and Sequeira, Frontiers Cell Dev Biology, 2021; Pereira et al, JID, 2023)
3. Investigating oral cancer genetic and microenvironment heterogeneity.
Tumour heterogeneity is one of the biggest challenges for cancer therapy as it is considered one of the main causes of therapeutic failure. Recent sequencing studies have highlighted the genetic heterogeneity of oral cancer, which is considered the basis of tumour microenvironment heterogeneity (including immune cell infiltrate, angiogenesis and remodelling of the tumour stroma). Our multidisciplinary lab combines leading edge tools in multi-omics, integrative genome analysis of tumour evolution, organoids culture, animal models of carcinogenesis, multiplex imaging analysis and application of artificial intelligence methods to map the cellular heterogeneity, behaviour and gene expression.
(Sequeira et al, Nature Communications, 2020; Kumar et al, Cancer Research, 2023)
4. Uncovering the immunoregulatory role of keratins. Keratins role in immunity has largely gone ignored and unstudied. We have revealed the importance of keratins as immunomodulator (Sequeira et al, Nature Communications, 2018). Our research brings a completely novel angle to the role of keratins in regulating immunity, enhancing our knowledge of autoimmune and skin inflammatory diseases.
More info in the lab webpage: www.sequeira.science
Publications
View all Publications at: https://orcid.org/0000-0003-3342-665X
Selected publications:
Moon JS, Ho CC, Jong-Hyun Park JH, Shin BY, Kim JH, Kim BS, Park K, Sequeira I, Mun CH, Son JY, Shin JS, Cho H, Oh JW, Lee SW, Morio T, Watt FM, Seong RH, Lee SK (2023). Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis. Nature Communications. doi.org/10.1038/s41467-023-40986-4
Caetano AJ, HCA Oral and Craniofacial Biological Network, Byrd KM*, Sequeira I* (2022). A Roadmap for the Human Oral and Craniofacial Cell Atlas. J Dent Research. Human Cell Atlas Publications. doi: 10.1177/00220345221110768
Bassler MC, Stefanakis M, Sequeira I, Ostertag E, Wagner A, Bartsch JW, Roeßler M, Mandic R, Reddmann EF, Lorenz A, Rebner K, Brecht M (2021). Comparison of Whiskbroom and Pushbroom darkfield elastic light scattering spectroscopic imaging for head and neck cancer identification in a mouse model. Analytical and Bioanalytical Chemistry. doi.org/10.1007/s00216-021-03726-5
Pereira D, Sequeira I* (2021). A Scarless Healing Tale: Comparing Homeostasis and Wound Healing of Oral Mucosa with Skin and Oesophagus. Invited Review for Frontiers in Cell and Developmental Biology. doi: 10.3389/fcell.2021.682143
Huang N, Perez P, […], NIH COVID-19 Autopsy Consortium, HCA Oral and Craniofacial Biological Network#, Teichmann SA, Warner BM, Byrd K (2021). # Byrd K, Sequeira I, Warner BM, Teichmann SA, Freire M, Kimple A. SARS-CoV-2 Infection in the Oral Cavity and Saliva. Nature Medicine. doi:10.1038/s41591-021-01296-8
Sequeira I, Rashid M, Tomas I, Williams M, Graham T, Adams D, Vigilante A, Watt FM (2020). The genomic landscape and clonal selection of carcinogen-induced mouse oral squamous cell carcinoma. Nature Communications. doi:10.1038/s41467-020-19401-9
Joost S, Annusver K, Jacob T, Sun X, Sivan U, Dalessandri T, Sequeira I, Sandberg R, Kasper M (2020). The molecular anatomy of mouse skin during hair growth and rest. Cell Stem Cell. doi: 10.1016/j.stem.2020.01.012
Byrd KM, Piehl NC, Patel JH, Huh WJ, Sequeira I, Marangoni P, Lough KJ, Wagner BL, Marangoni P, Watt FM, Klein OD, Coffey RJ, Williams SE (2019). Heterogeneity Within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress. Cell Stem Cell. doi: 10.1016/j.stem.2019.11.005
Girardeau-Hubert S, Deneuville C, Pageon H, Abed K, Tacheau C, Cavusoglu N, Donavan R, Bernard D, Asselineau D, Sequeira I (2019). Epidermal differentiation and proliferation heterogeneity in skin color types. J Inv Dermatology. doi: 10.1016/j.jid.2019.07.234
Sequeira I, Watt FM (2019). The role of keratins in modulating carcinogenesis via communication with cells of the immune system. Invited Review for Cell Stress. doi: 10.15698/cst2019.04.184
Sequeira I, Neves JF, Carrero D, Peng Q, Palasz N, Liakath-Ali K, Morgan P, Graham L, Lombardi G, Watt FM (2018). Immunomodulatory role of Keratin 76 in oral and gastric cancer. Nature Communications. 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 (2018). An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis. Nature. doi: 10.1038/s41586-018-0032-3
Telerman S, Rognoni E, Sequeira I, Pisco AO, Lichtenberger BM, Culley O, Viswanathan P, Driskell R, Watt FM (2017). Dermal Blimp1 acts downstream of epidermal TGFβ and Wnt/β-catenin to regulate hair follicle formation and growth. J Inv Dermatology. doi: 10.1016/j.jid.2017.06.015
Weber C, Telerman SB, Sequeira I, Liakath-Ali K, Reimer AS, Arwert EN, Watt FM (2016). MEK1-induced, wound-mediated skin carcinogenesis depends on macrophage recruitment and a switch in macrophage activation during wound healing. Cancer Research. doi: 10.1158/0008-5472.CAN-14-3676
