Assoc. Prof. Hani
Alotaibi

For the past 15 years I have been involved in several projects mainly focusing on deciphering mechanisms of transcriptional regulation. During my Ph.D., we focused on the transcriptional regulation of the sodium iodide symporter (NIS) gene, and identified two distinct activators playing a critical role in the initiation and maintenance of expression. Estrogen receptor alpha (ERa) appeared to be crucial for the initiation of transcription as it directly binds the promoter (Alotaibi et al 2006). We also identified retinoic acid receptor alpha (RARa) as the second major regulator of NIS expression, and detailed the mechanism by which it interacts with intronic enhancers to achieve rapid and potent expression (Alotaibi et al 2010). Later on, during my postdoctoral training, I was responsible for exploring the transcriptional regulation of E-cadherin. This lead to the identification of Grhl3 and Hnf4a as the major regulators, and that Grhl3 is a critical factor for the initiation of transcription especially during the process of mesenchymal to epithelial transition – MET (Alotaibi et al 2015). We then became interested in understanding how MET is transcriptionally regulated and we are currently working on resolving the transcriptional networks controlling the mesenchymal to epithelial transition (MET). Recently we have identified a feed forward loop, which is composed of the transcription factors Grhl3 and Hnf4a that are essential for the progression of MET. Our preliminary data suggest the existence of several overlapping transcriptional nodes having Grhl3 in the centre of a larger network and E-cadherin as the major outcome. Our main goal is to confirm the transcriptional relationships between the identified transcription factors and to draw a more comprehensive picture of the MET network. As a result we aim to identify a core MET network, which, in the long run, would lead to the identification of therapeutic targets for a better management of MET during metastasis. MET is also a critical step during the reprogramming of iPSCs, thus identifying a core MET network could be utilised to improve the efficiency and quality of the reprogramming process.