Research

Our Research

Creation of physiologically relevant cellular models of disease through genome engineering of induced pluripotent stem cell (iPSC) models.

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Creation of physiologically relevant cellular models of disease through genome engineering of induced pluripotent stem cell (iPSC) models. We routinely generate homogeneous macrophages which we exploit to better understand immune susceptibility to pathogens and disease. iPSCs are also used to generate human umbilical vein endothelial cells to study innate immune response. Furthermore, we create isogenic iPSCs which contain sub-Saharan relevant SNPs involved in adverse drug reactions to assess the effects of toxicity in iPSC derived liver cells.

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Using sequencing, bioinformatic and two- and three-dimensional microscopy-based tools to map out the chromatin landscape of primary cancer cells in an African context.

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Using sequencing, bioinformatic and two- and three-dimensional microscopy-based tools to map out the chromatin landscape of primary cancer cells in an African context. This work aims to recapitulate cancer-specific chromatin arrangements and transcriptional profiles in induced pluripotent stem cell (iPSC) models and primary tumors to identify prognostic and druggable configurations.

Understanding different aspects of mRNA localization and translational regulation, including identifying and characterizing key RNA and protein players.

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A large number of mRNAs exhibit tightly controlled localization patterns specific to particular cell types, which can act as determinants of protein subcellular localization through local translation. In my work, I focus on understanding different aspects of mRNA localization and translational regulation, including identifying and characterizing key RNA and protein players. As part of this work, we established DypFISH an image-based novel method to explore and analyze the distribution and subcellular localization of different molecules within cells.

Uncontrolled activation of the immune system is the etiology of many disorders with an inflammatory basis, such as inflammatory bowel disease, cancer, autoimmune disease and severe sepsis.

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Uncontrolled activation of the immune system is the etiology of many disorders with an inflammatory basis, such as inflammatory bowel disease, cancer, autoimmune disease and severe sepsis.  Gene regulation, or the mechanism whereby genes are switched on and off, is critical to inflammatory processes. However, the molecular mechanism whereby this occurs remains incomplete. My work focuses on understanding how nuclear architecture and lncRNA-based mechanisms contribute to immune gene regulation. This is achieved using the combination of advanced microscopy and molecular biology approaches, including chromosome conformation capture technologies; chromatin immunopreciptation; genome editing technologies (eg.TALENs, CRISPR) and single cell microscopy techniques (eg. single molecule fluorescent in situ hybridization). By gaining a detailed understanding of these processes, we will be able to develop therapeutic strategies that more precisely and discretely treat these inflammatory disorders

Gene expression heterogeneity and drug response of the cancer cells at single cell level by using next generation sequencing and bioinformatic tools.

aAlthough various methods have been developed to treat cancer, cancer is still leading lethal disease in the world. The biggest barrier to treat cancer is drug resistance caused by cancer heterogeneity. However, it remains unknown how heterogeneity contribute to drug resistance. In an attempt to understand this, we study gene expression heterogeneity and drug response of the cancer cells at single cell level by using next generation sequencing and bioinformatic tools. This study will give us a new insights moving into tumour precision medicine.

Long-range chromatin contacts form multi-gene complexes by bringing genes into close spatial proximity.

aLong-range chromatin contacts form multi-gene complexes by bringing genes into close spatial proximity. Through the formation of these three-dimensional conformations, the transcription of spatially segregated genes (in 1D space) can be highly coordinated and co-regulated. The observation of such long-range chromosomal interactions and the resultant gene transcription, in living cells, is particularly challenging due to their dynamic nature. Our work involves developing a discrete system that is able to specifically label chromosomal loci and nascent transcription allowing us to study the dynamics of chromatin contacts and gene transcription in living cells. In order to do this, we use various DNA manipulation, genome editing and live cell microscopy techniques.

Pathogens alter host gene regulation to create a favourable environment for infection.

aPathogens alter host gene regulation to create a favourable environment for infection. What may seem as a homogenous process of infection in a population of cells, however, can be vastly heterogeneous whereby individual host cells respond differently by having different gene expression profiles. We use an intracellular bacterial pathogen as a model to understand the molecular mechanisms behind transcriptional control in the host and how this difference contributes to infection outcomes. By using advanced imaging techniques, we can detect active transcription while following the process of infection in single cells.