Steven Stacker lab

Oliver CUCANIC, Rae Farnsworth and Steven Stacker

Organ-specific metastasis of cancer cells from the primary tumour to secondary organs, including lungs, depends on the formation of a supportive microenvironment called the pre-metastatic niche. Extravasation of cancer cells into secondary organs is a key event in metastatic progression, facilitated by vascular hyperpermeability induced by cellular mediators. However, the mechanisms involved are not well understood, and the role of lung endothelial cell diversity in metastasis is unknown. Herein, we aim to utilise single-cell RNA sequencing to understand the lung-specific vasculature's role in cancer metastasis to elucidate predictive, prognostic, and therapeutic markers that may be used to mediate metastasis. 

Lucas Tobar, Rae Farnsworth and Steven Stacker 

The brain is a frequent site of metastasis, and often fatal, due to the critical role of the nervous system and the limited options for treatment including surgery. Local changes in the vascular network, immune system and stromal components all have the potential to recruit and foster metastatic tumour cells. This project will use cutting-edge experimental techniques such as single-cell RNA sequencing (scRNAseq) to define the molecular changes within vascular environments and alterations in specialized subsets of blood and lymphatic vessel cells at various stages of cancer spread to the brain and meninges.

Aadya Nagpal, Rae Farnsworth and Steven Stacker 

It has been known for centuries that the presence of tumour cells in a regional lymph node portends a poor prognosis, but the role of lymph nodes in fatal metastasis to major organs remains unclear. Lymph nodes are uniquely positioned to receive lymphatic drainage of cells and molecules directly from the tumour, enabling them to act as sentinels. Notably, lymph node lymphatic and blood vessels can begin to change even before the arrival of metastasising tumour cells. We are using single cell RNA Sequencing technology to interrogate molecular alterations in lymph node vessels prior to tumour cell arrival to understand the earliest events of regional lymph node metastasis. 

Rae Farnsworth and Steven Stacker 

CAR T cell therapy involves engineering the patient’s own immune cells to express a Chimeric Antigen Receptor (CAR), which enables them to specifically seek and destroy tumour cells that display a certain molecular target. This therapy has had many successes, but the molecular diversity of cancer necessitates development of new CAR T cell targets. We are developing and testing a novel CAR T cell targeted to RYK, a cell surface receptor involved in cancer cell survival and metastasis. RYK is highly expressed in many cancer types relative to normal tissues, and also on nonmalignant cells within tumours, making it a promising new target for solid cancers. 

Kathleen Dominic, Aadya Nagpal and Steven Stacker 

The spread of cancer cells from its primary site of growth to distant organs is a major cause of cancer-related mortality in patients. Furthermore, acquired resistance to the current standard of care cytotoxic/radiation therapies leads to treatment failure in patients with advanced disease. Hence, it is critical to identify the key mechanisms underlying cancer spread and therapy resistance to improve patient outcomes. We are using functional cell biological assays, molecular biology techniques, advanced microscopy and preclinical models to understand the role of RYK receptor (a key growth promoting cell surface protein) in regulating cancer progression as well as therapy response.