Jana Obajdin
Academic and Work Experience Prior to Sept 2016 Programme Start
I obtained a Bachelor’s degree in Biochemistry with a Year in Industry at the University of Leeds. During this time, I spent a year working in the Investigative Toxicology group at UCB BIoPharma in Belgium exploring novel biomarkers of drug-induced kidney injury for toxicity assessments.
I then completed my undergraduate thesis project in the lab of Alan Berry working on structural studies to uncover the crystal structure of IdmH, a putative polyketide cyclase and an enzymatic component of the NRPS/PKS system which generates the antibiotic indanomycin.
PhD Programme – Year 1 – MRes and Project Rotations
During my first year of the Wellcome Trust 'Cell Therapies and Regenerative Medicine' Four-Year PhD Programme I completed three different rotations:
I worked under the supervision of Dr Alessandra Vigilante, using bioinformatic tools to assess genetic factors which contribute to HIV-1 infectivity levels using human induced pluripotent stem cell (hIPSC) lines.
Under the supervision of Dr Joana Neves and Dr Franziska Denk, I established a triple co-culture system between small intestinal organoids, sensory neurons and innate lymphoid cells type 2 (ILC2s) to study neuro-immune-epithelial interactions.
My final rotation was spent in the lab of Dr John Maher where also under the supervision of Dr Marc Davies, I worked on generating chimeric antigen receptor (CAR) T-cells and assessing their efficacy against solid tumours.
PhD Programme – Years 2 to 4 – Doctoral Studies
CD8+ T-cells are predominantly responsible for the detection and elimination of cancerous cells, recognising tumour-associated antigens (TAAs) presented on major histocompatibility complex (MHC) molecules via their T-cell receptor (TCR). However, tumours may adapt by downregulating MHC expression or altering TAAs. Chimeric antigen receptor (CAR) T-cells are genetically modified to express TAA-specific receptors, expanding the repertoire of targetable antigens without MHC restriction.
Effective T-cell activation requires a stimulatory signal provided by TCR components and a co-stimulatory receptor signal. First-generation CARs provided only the stimulatory component, however second-generation constructs incorporating the additional co-stimulatory domain demonstrate superiority. We will generate second-generation CARs using the activating natural killer cell group 2D (NKG2D) receptor as the targeting moiety. NKG2D targets eight ligands expressed on most haematological and solid tumours, expressed at low levels on healthy tissue, and upregulated specifically in transformed cells. We will be comparing previously described NKG2D CARs for their ability to re-target T-cell specificity against a range of solid tumour cell lines and generate novel constructs which encompass different variations of activating and co-stimulatory components.
We will assess anti-tumour efficacy, cytokine secretion and safety both in vitro and mouse xenograft models. We then plan to conduct an RNAseq analysis to compare CAR T-cells with varying anti-tumour potencies to uncover key differentially expressed genes which contribute to the phenotypic and functional differences, and mechanistic insights into their efficacy, including information on signalling pathways activated, their metabolic status and differentiation.
