Cher Shen Kiar
Academic and Work Experience Prior to Sept 2020 Programme Start
At UCL, I received my undergraduate degree in Biochemistry with a Year in Industry undertaken at Protein Technologies group, GlaxoSmithKline Stevenage.
In the past, I was fascinated by the mechanisms of molecular machines that are responsible for the correct functioning of cells. Under Dr Lisa Cabrita's supervision, I explored various methodologies to create 'snapshots' of protein biogenesis to probe the co-translational protein (mis)folding facilitated by the ribosomes.
At GSK, I received excellent mentorship from Dr Maja Firczuk and Dr Michael Mullin; I was entrusted to lead the expression technology project which sought to improve mammalian protein expression and secretion through the design of regulatory genetic circuits. Here, I developed a high-throughput secretion assay and investigated the influence of differential codon adaptation in mammalian secretion efficiency. The experience was intellectually stimulating and rewarding for me as a scientist to contribute to the delivery of innovative, life-saving medicines.
PhD Programme- Year 1- MRes and Project Rotations
I spent my first year exploring various aspects of cell biology and regenerative medicine. In my first rotation supervised by Prof Francesca Spagnoli, I worked on developing CRISPR/Cas9 approach for ex vivo pancreatic culture and probing the influence of extracellular matrix in pancreatic development using ex vivo pancreas model. For the second rotation, I worked with Dr Subhankar Mukhopadhyay to explore the influence of malignant tissue signals on macrophage gene expression through single-cell RNA sequencing analysis. Finally, my third rotation supervised by Dr Alessandra Vigilante sought to build a bioinformatic pipeline for tumour-derived cell-free DNA, to identify predictive clinical markers for metastatic pancreatic cancer.
PhD Programme- Years 2 to 4- Doctoral Studies
Tissue-resident macrophages are highly heterogeneous populations of innate immune cells residing in all tissues as a dispersed organ, with crucial homeostatic, physiological and immunological functions. Their remarkable diversity is dependent on their developmental origins, tissue niche-specific signals and stimulus-dependent activations; however the underlying mechanisms for generating such diversity remain unclear. Studying these cells are difficult as they quickly lose their tissue specificity upon retrieval from specific tissue niches.
For my PhD project, I am working with Dr Subhankar Mukhopadhyay and Dr Andrew Bassett:
to establish methods for converting iPSCs into different tissue-resident macrophages,
to characterise the differences in their epigenetic and metabolic landscapes, and
to generate iPSC-derived ‘designer’ macrophages through synthetic biology approach and examine their preclinical safety and efficacy as cell therapy.
The overall goal for this project is to uncover the molecular control mechanism of diverse macrophage cell fates; with this understanding, we will pioneer the rational design and engineering of iPSC-derived macrophages as advanced therapy to address the unmet medical need in cancer, inflammatory-associated diseases and other macrophage-driven pathologies.
