BSc (Hons), PhD
Marshall-Smith Syndrome (MSS) is a congenital disorder affecting skeletal and neural development due to mutations in the nuclear factor I/X (NFIX) gene. These mutations introduce frame shifts and splice site variants, which result in the production of aberrant transcripts, leading to the production of dysfunctional mutant NFIX proteins. NFIX is a transcription factor that regulates gene expression in many tissues, including lung, kidney, liver, blood, heart, skeleton and nervous system. It binds as homo- or hetero- dimers to the promoter regions of genes where it can act as either a suppressor or activator of gene transcription.
My postdoctoral research focuses on understanding the role of NFIX in the pathogenesis of Marshall-Smith Syndrome and to identify potential treatments for MSS by using a wide range of basic molecular and cellular biology techniques such as cloning techniques, PCR, RT-qPCR, RNA sequencing, western blot, immunohistochemistry, cell culture, cell transfections, microscopy and in vitro expression and reporter assays. My work predominantly focuses on (i) elucidating the mechanisms of action of MSS-associated NFIX mutations on NFIX activity in order to gain greater insight into the role of MSS-associated NFIX mutations in bone development; (ii) identifying pathways that are differentially altered by the MSS-associated NFIX mutations which may represent potential targets for drugs; (iii) identifying compounds that could modulate NFIX activity; and (iv) assessing the efficacy of compounds at modulating NFIX activity and their use as possible treatments for MSS. Prior to starting my postdoctoral work in Oxford, I completed an undergraduate degree in Biological Sciences (Genetics) from the University of Birmingham and a PhD in Genetics from the University of Cambridge, where I investigated pathways and mechanisms of epigenetics and RNA interference. I am a member of the Genetics Society and the Society for Endocrinology.
Ap2s1 mutation causes hypercalcaemia in mice and impairs interaction between calcium-sensing receptor and adaptor protein-2.
Hannan FM. et al, (2021), Hum Mol Genet
Multiple Endocrine Neoplasia Type 1 (MEN1) Phenocopy Due to a Cell Cycle Division 73 (CDC73) Variant.
Lines KE. et al, (2020), J Endocr Soc, 4
Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.
Mulder PA. et al, (2020), J Intellect Disabil Res
Multiple endocrine neoplasia type 1 (MEN1) 5' UTR deletion, in MEN1 family, decreases menin expression.
Kooblall KG. et al, (2020), J Bone Miner Res
Detection of neutralising antibodies to SARS coronavirus 2 to determine population exposure in Scottish blood donors between March and May 2020
THOMPSON C. et al, (2020), Working paper