Abigail Isaacson
Academic work and experience prior to September 2019
I completed my Master’s degree in regenerative medicine at UCL and afterwards gained experience in corneal tissue engineering using 3D bioprinting at Newcastle University.
Following this, I worked as a research assistant at the Sanger Institute where I helped to establish a pipeline for genetic knockout studies on induced pluripotent stem cell (iPSC)-derived hepatocytes.
PhD Programme- Year 1- MRes and Project Rotations
This particular PhD programme interested me because of the broad interdisciplinary research carried out at King's and the training in both computational and experimental methods for this purpose.
During my MRes year I completed 3 different rotation projects that were wide-ranging and encompassed research into in situ tissue regeneration, muscular dystrophy, and the discovery of a novel mutation implicated in monogenic diabetes. I undertook my first rotation project in Professor Abigail Tucker's lab where I monitored the movement of potential stem cell populations during eardrum repair, both in vivo and in eardrum explants.
During my second rotation project in Professor Peter Zammit’s lab, I focused on the computational prediction of regulators of DUX4, a gene that is derepressed in Facioscapulohumeral muscular dystrophy (FSHD), from single-cell trajectory data.
I completed my final rotation project during the UK COVID-19 lockdown in Dr Francesca Spagnoli’s lab where I carried out gene ontology term enrichment analysis on differently expressed genes during different stages of in vitro pancreatic beta cell differentiation of a mutant iPSC line. The mutation introduced into this cell line had previously been identified as a disease-causing candidate in a cohort of patients with early-onset diabetes. The skills I gained during this year were enhanced by the many different workshops provided by King’s that enabled me to take a comprehensive approach when tackling different scientific questions.
PhD Programme- Years 2 to 4- Doctoral Studies
For my PhD project I have joined Dr Spagnoli’s lab in the Centre for Stem Cells and Regenerative Medicine. I am interested in understanding the molecular mechanisms underlying development and the maintenance of cell identity with a view to harnessing these for the generation of cell therapies. My PhD project is aimed at understanding the function of Pbx1, a homeodomain transcription factor, in both the developing and adult pancreas.
Pbx1 activity is essential for early pancreatic development as embryos with homozygous deficiency of Pbx1 exhibit pancreatic hypoplasia and cell differentiation defects prior to death in utero at E15.5. Using a conditional Cre-Lox system, we will focus on Pbx1 deletion in pancreatic epithelium at various stages of mouse development and in the adult pancreas. I will establish an iPSC model to assess whether developmental mechanisms involving Pbx1 observed in mice are also conserved in humans. I will also construct a gene regulatory network of the pancreatic epithelium using Chromatin Immunoprecipitation (ChIP) and RNA sequencing data at various developmental stages to test Pbx1 targets. This project has great potential for advancing the field of diabetes research and for the in vitro recapitulation of pancreatic development for cell therapies.
