Thea Willis
Academic and Work Experience Prior to Sept 2018 Programme Start
I completed my undergraduate degree in Molecular and Cellular Biology at the University of Bath. During my degree, I undertook a placement year to research novel autophagy adaptor proteins in redox homeostasis under Professor Luo at the Peninsula Schools of Medicine and Dentistry.
When I returned to Bath for my final year, I joined Professor Tosh’s lab where I was involved in the characterization of novel transcription factors associated with transdifferentiation events that occur in Barrett’s Oesophagus disease.
PhD Programme – Year 1 – MRes and Project Rotations
For my first rotation I worked with Dr Guermonprez to optimise the differentiation of iPSCs into hematopoietic stem cells and dendritic cells.
During my second rotation with Dr Andoniadou I learnt how to analyse single cell RNA sequencing data using bioinformatics and used this to investigate heterogeneity in the stem cell compartment of the pituitary gland. As well as learning some bioinformatics, I used mouse models and in vitro staining techniques to learn about these novel sub-populations (see image).
For my final rotation I joined the lab of Dr Charalambous to research the transcriptional regulation of ZAC1 on imprinted genes using CUT&RUN, a new epigenomic profiling strategy.
PhD Programme – Years 2 to 4 – Doctoral Studies
For my PhD project I have chosen to join the lab of Dr Cynthia Andoniadou to investigate the stem cell population of the pituitary. The pituitary gland controls processes such as growth, pregnancy, response to stress and metabolism. Subsequently, this gland has to remain plastic to respond to ever-changing demands for hormones throughout life, and does so, in part, through changes in the tissue-specific stem cell population.
This stem cell population is inherently heterogenous, with undefined subgroups promoting self-renewal, whilst others commit to hormone-specific lineages or remain quiescent. Furthermore, recent data from our lab has implicated Hippo pathway effector proteins YAP/TAZ as crucial for maintaining homeostasis within the stem cell population, with dysregulation causing tumourigenesis. In addition, WNT ligands have been shown to be secreted from a subgroup of the stem cells, promoting the proliferation of fate-determined progenitor populations to maintain the postnatal gland. Two branches of novel investigations are necessary to elucidate the importance and function of different subgroups within this heterogenous stem cell population.
Firstly, bioinformatic approaches will be utilised to identify specific subpopulation markers for assessment of stem cell potential and function in vitro and in vivo. Secondly, levels of interplay between Hippo and WNT signalling will be assessed in these cells, utilising proximal-protein interaction assays and analyses of mutant murine lines. Uncovering the extent of heterogeneity within the postnatal pituitary stem cell compartment and cross-talk between the WNT and Hippo pathways is key to understanding their potential for regenerative therapies to treat prevalent pituitary disorders.
