MRC Molecular Haematology Unit
MRC Weatherall Institute of Molecular Medicine
Senior Postdoctoral Researcher
Cis-Regulatory Sequence Characteristics and Gene Regulation
I am a senior Postdoctoral Researcher working with Prof. Doug Higgs in the MRC Molecular Hematology Unit at the MRC Weatherall Institute of Molecular Medicine, University of Oxford, studying how genes are switched on and off in development, differentiation and disease.
My research focuses on what characterises the linear DNA sequence underlying cis-regulatory elements (mainly enhancers) in mammalian genomes. More specifically, I am studying the impact of enhancers' sequence orientation and position within a regulatory landscape on gene regulation.
In more detail
Throughout my academic training, I have been interested in how genes are switched on and off, the outstanding question that underlies the complexity of living organisms. Addressing the topic from both, the regulatory protein and DNA sequence perspectives, I have used the hematopoietic system (and red cells in particular, erythropoiesis) as the model of choice:
1- In my D.Phil and first postdoctoral project, I focused on a tissue-specific transcription factor (Tal-1) and studied the effect of its recruitment to regulatory DNA sequences on gene regulation genome-wide. In the process, I have developed an in depth theoretical knowledge and technical expertise that allowed me to maintain and genetically manipulate mouse Embryonic Stem (ES) cells, and produce and analyse both in vivo and in vitro mammalian models to test my hypotheses.
2- In my current research position, I am focusing on enhancer biology. Using state of the art molecular biology tools, I inverted the sequence encompassing the regulatory elements in the alpha-globin locus and dissected its effect on the genomic architecture and gene expression.
In my co-supervisory role of Helena Francis, a Wellcome Trust Chromosome and Developmental Biology D.Phil student, we examine in detail the effect of sequence and context perturbation on the function of a single enhancer in the alpha-globin locus. In the process, we have developed an in vitro miniaturised mouse ES hematopoietic differentiation system for high throughput manipulation and screening of genetically-modified mouse ES cells.
Following on from my projects' findings, I will continue my pursuit of unravelling how the linear organisation of genomic elements impacts on gene regulation, both in normal and pathological contexts.
I am co-founder and current president of Innovation Forum Oxford, a non-for-profit organisation, part of a global organisation, run by "scientists for scientists" with the mission to inspire, educate, and empower scientific researchers to recognise the value of their research and harness their findings for the benefit of human health. Lowering the barriers for knowledge exchange and collaborations with the outside world (industry, NHS, policy makers, enablers) is at the heart of the events we design and deliver. This has been acknowledged by the University of Oxford as we were awarded the Knowledge Exchange Seed Fund for our 2018 workshop series (ACE saturdays) and three independent nominations (MRC WIMM, MSD Business Development Office, OUI) for the 2018 Vice-chancellor Inaugural Innovation Award.
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After completing my BSc at the American University of Beirut (AUB), I was awarded Karim Rida Said Foundation (KRSF) scholarships to complete my graduate studies in the UK; an MSc in Human Genetics at Brunel University and a D.Phil at the University of Oxford.
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Scalable in vitro production of defined mouse erythroblasts.
Francis HS. et al, (2022), PLoS One, 17
Reactivation of a developmentally silenced embryonic globin gene.
King AJ. et al, (2021), Nat Commun, 12
The mouse alpha-globin cluster: a paradigm for studying genome regulation and organization.
Oudelaar AM. et al, (2021), Curr Opin Genet Dev, 67, 18 - 24
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.
Brown JM. et al, (2018), Nat Commun, 9
Between form and function: the complexity of genome folding.
Oudelaar AM. et al, (2017), Hum Mol Genet, 26, R208 - R215