Nicholas Clemons lab

Dr Ebtihal Mustafa (Postdoctoral), Dr Julia Milne (Postdoctoral), Ibukun Adejumobi (PhD candidate) 

1. Determining the cellular origin of metaplasia and cancer in the oesophagus - the goal of this project is to identify and study different progenitor cell populations in the oesophagus to determine where the pre-cancerous metaplastic condition known as Barrett's oesophagus comes from. This project will provide a detailed understanding of the natural history of this disease, including the role of the inflammatory microenvironment, with the future goal of developing treatments to prevent disease progression. Technical approaches include single-cell sequencing and spatial imaging technologies to characterise potential progenitor cells, and 3D-organoid models to study their functional differentiation capacity. Funded by NHMRC Ideas grant
   
   
2. Functional characterisation and categorisation of gastro-oesophageal cancer driver genes - the goal of this project is to perform a high-throughput, in-depth functional characterisation of gastro-oesophageal tumour suppressors and oncogenes. This new knowledge will allow us to group driver genes that have similar functional effects with the goal of developing therapies to treat groups of tumours driven by different driver genes. Technical approaches include boutique CRISPR knockout and activation screens, combined with single cell transcriptomics (Perturb-seq) and individual and combinatorial CRISPR perturbations in cell line xenograft and patient derived organoid models of oesophageal tumourigenesis. - funded by NHMRC Ideas grant 

Dr Julia Milne (Postdoctoral), Katherine Papastratos (Research Assistant), Zoe Nguyen (PhD candidate), KaMeng (Ben) Wu (Masters student) 

1. Improving therapeutic responses in oesophageal cancer by overcoming resistance to ferroptosis - in this project we are studying the role of different metabolic pathways in protecting gastro-oesophageal cancer cells from undergoing a form of cell death called "ferroptosis". The goal is to identify metabolites and metabolic pathways that can be targeted to overcome resistance of these cancers to treatment. Technical approaches include in vitro and in vivo combination therapy studies, and metabolomic, proteomic and metabolism gene focussed CRISPR knockout screens to identify cancer vulnerabilities. - funded by NHMRC Ideas grant 
    
2. Identifying synthetic lethal approaches to target gastro-oesophageal cancers - in this project we are leveraging the knowledge gained from our work characterising the functional effects of individual driver genes in gastro-oesophageal tumourigenesis to identify genes and pathways that these are dependent on and are thus potentially good therapeutic targets. Technical approaches include genome wide CRISPR knockout screens, live-cell imaging, cellular and molecular biology techniques and in vitro and in vivo drug studies. - funded by NHMRC Ideas grant, US Department of Defense Rare Cancers Research Program Concept Award and industry partnership with Astex Pharmaceuticals, UK. 
    
3. Gene modified pluripotent stem cells to generate and empower innate immune cells against poor-prognosis cancers - this project is a collaboration with Cartherics Pty Ltd to develop and perform pre-clinical evaluation of CAR-NK cells (derived from adult induced pluripotent stem cells) targeting an antigen expressed in ovarian and gastro-oesophageal cancers. Technical approaches include in vitro co-culture cell killing assays and adoptive transfer studies in mice with gastro-oesophageal cell line or patient derived xenografts. - funded my MRFF Stem Cell Therapies Fund.

Dr David Liu (Clinical Associate), Associate Professor Cuong Duong (Clinical Associate), Sasha Witts (Research Assistant), Mike Bozin (PhD candidate), Zexi Allan (PhD candidate)