MODEL SYSTEMS AND TECHNOLOGIES

Human somatic (such as blood stem cells) and pluripotent stem cells (such as embryonic stem cell lines) share common distinct pathways. In studying both, we have gained deeper insights. Similarly, cancerous adult stem cells and cancerous pluripotent stem cells share many properties that are distinct from other cancer cells that make up a tumour. Uniquely, our approach is to study both adult and pluripotent cells in their normal and cancerous states. This allows us to ask scientific questions and explore novel therapeutic approaches that are unique to our program and expertise. Most recently, to unlock the complex heterogeneous system of healthy tissue and cancerous tumour, we are using and developing novel approaches of multi-cytomics (single cell RNAseq, flow and image-based cytometry, clonal tracking).

Our research focuses currently on tissue restricted bone marrow blood stem cells and previously on embryonic stem cell lines. As research in this area has advanced worldwide, so have our options and we now use “induced pluripotent stem cells”. These cells are obtained using Nobel Prize winning “cell reprogramming” technology to reverse cell fate decisions in adult cells. We have further developed an approach to identify and characterise pluripotent cell lines at the earliest stages of cell fate transformation to cancerous states, which has been an instrumental tool for our program in unlocking new candidate therapies.

Our human cancer stem cell and pluripotent stem cell screening platform represents an important and proprietary component of our program being developed over the last decade. This platform focuses on identifying anti-cancer “hits” for cancers using AML as the gateway disease, which is being extended to include breast, colon and brain tumours, and accesses novel chemical space for these ongoing studies. 

We have revealed the influences on cancer stem cells from the microenvironment or “niche” in patients, and we have created a suite of tools from human assays to high content screens for chemical genomics and lead target/drug discovery, which we have moved into Phase I trials. This suite of tools forms the basis of our model systems and platform technologies, and engine of our research program.

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With work previously done by a former lab member, we have developed a powerful tool for use in the identification and characterization of the processes in our model system. A major advantage of this development is its improved sensitivity, which allows it to detect subtle dynamic property changes in response to our experimentation.