Research

What we do

Quality control of new cells, tissues and organs

Led by George and Dorian

We aim to automate the quality control of lab-grown cells, tissues and organs with single-cell and spatial resolution. This is key to integrate both models of rare disease and tissues and organs into routine translation and transplantation, respectively.

Collaboration with Prof Kurian and Prof de Coppi.

Budinger et al.

An in vivo and in vitro spatiotemporal atlas of human midbrain development

bioRxiv

Hall and Castellano

Dawnn: single-cell differential abundance with neural networks

bioRxiv

Other manuscripts in preparation.

Figure. Spatial distribution of (almost) single cells in a new organ post-transplant.

Rapid skin sheets for gene therapy

Led by Vignesh and George

We aim to accelerate the growth of engineered epithelial grafts for skin rare diseases while preserving their self-renewal properties.

Co-supervise with Prof Li and funded by the MRC.

Jayarajan et al.

Short-term keratinocyte Rho-associated kinase inhibitor treatment accelerates primary keratinocyte growth while preserving stem cell characteristics

Cells, 12, 346 (2023)

Figure. Accelerated differentiation and proliferation of keratinocytes, tracked at single-cells resolution

Natural history of micronutrient deficiencies

Led by Jas

We aim to understand the pattern of local adaptation to micronutrient deficiencies (Selenium, Zinc, Iron and others) as humans migrated around the world. These deficiencies are a global health burden worldwide and particularly prevalent during pregnancy and early childhood.

Rees et al.

Ancient loss of catalytic selenocysteine spurred convergent adaptation in a mammalian oxidoreductase

Genome Biology and Evolution (2024)

Other manuscripts in preparation.

Figure: Signatures of selection across world-wide human populations in micronutrient genes

Determinants of iPSC differentiation success

Led by Pau

We aim to understand which factors drive the success of iPSC models of development or rare disease. As it happens, the in vitro accumulation of deleterious variation likely plays a major role. See bioRxiv manuscript.

Co-supervised with Assistant Prof Kilipinen, now in Helsinki. Funded by the GOSH BRC and Wellcome (to Kilpinen)

Puigdevall et al.

Effects of somatic mutations on cellular differentiation in iPSC models of neurodevelopment

Cell Genomics, 3, 100280 (2023)

Figure. Excess of deleterious variation in the BCOR gene during dopaminergic differentiation.

Severe pre-eclampsia: molecular causes and consequences

Led by Dorian, Yara, Jose and Leysa

We aim to unveil the molecular underpinning of pre-eclampsia, which has no treatment and only resolves upon delivery. We apply single-cell and spatial transcriptomics to interrogate the maternal-fatal interface throughout gestation as well as interrogating potential infections.

CHI and other placental diseases also under investigation.

Co-supervised with Associate Prof Hillman Dr Kristiansen and Prof Sebire. Funded by the MRC.

Manuscripts in preparation.

Figure. Single-cell deconvolution of cell types across a tissue slide of the placenta.

Childhood Leukaemias: treatment, resis-tance and CAR-T targets

Led by Ilaria, Eduardo and George

We aim to profile resistant cells in CML and AML at single-cell resolution, including the transcriptome, surface proteome and driving mutations. We also test CAR-T properties as well as their life cycle, from infusion to expansion. See bioRxiv manuscript.

Mainly supervised by Associate Prof Giustacchini (now also Group Leader at the Human Technophole). Funded by TAS, AMS (to Giustacchini), CRUK and the GOSH BRC.

Michelozzi et al.

Enhanced functionality of low-affinity CD19 CAR T-cells is associated with activation priming and a polyfunctional cytokine phenotype

Blood Advances, 7, 1725–1738 (2023)

Figure. Individual cells carrying the BCR-ABL mutation, in red.

Assessing Genomic Risks in gene therapy

Led by Dimah

We aim to provide quick and robust measures of viral vector integrations in patients undergoing gene therapy. We apply highly optimised capture and enrichment approaches, followed by stringent computational analysis. It is applicable to natural infections.

Co-supervised with Dr Williams and funded by KACST.

Morfopoulou et al.

Genomic investigations of acute hepatitis of unknown aetiology in children

Nature, 617, 564–573 (2023)

Figure. Sensitivity and specificity of the identification of viral vector integrations in the genome at different stringencies.