Basic Research

There is a wide range of cancer research being conducted in Nova Scotia. The following studies are related to cell cycle regulation and the development of cancer:

Dr. Brent Johnston is working to understand how white blood cells move from the blood to the tissues in order to protect the body from foreign pathogens and cancerous cells. Natural Killer T (NKT) cells are a type of white blood cell, which play an important role in the control of cancer cells and have been shown to induce potent tumor responses. Dr. Johnston is working to identify the molecules that tell NKT cells where to go and when to turn on their anti-tumor functions. This information could possibly be used to develop therapies that direct NKT cells to kill tumors more efficiently in cancer patients, or prevent the spread of cancer cells to other tissues. 

The primary focus of Dr. Paola Marignani's laboratory is to understand how and why we get cancer. To do this Dr. Marignani uses cutting edge proteomic and genomic strategies that allow her and her team to study the communication or signaling pathways between groups of proteins that have developed changes or mutations. These mutations are damaging and lead to the development of cancer and sometimes other serious diseases. Once the mutations in the proteins and the errors in signaling pathways between different proteins have been identified, Dr. Marignani will use these findings to correct the mutations that will return the communication between the groups of proteins back to normal. Dr. Marignani's research program will lead to the development of better treatments for cancer and hopefully cures for cancer.

Cancer cells are essentially cells that have lost the ability to stop growing. Signal transduction is how cells communicate with their environment and is one of several important processes cells use to decide whether they will grow or not. Dr. Christopher McMaster's research is identifying the signaling processes cells use to regulate their growth. His goal is to pinpoint new targets for the development of better cancer fighting drugs.

Dr. Catherine Too is primarily interested in prolactin receptor (PRLP) action in PRL-responsive tumor cells such as lymphomas and breast cancers. PRL is a natural hormone in the body with a wide spectrum of action such as regulating normal immune cell function and mammary (milk) gland development. However, PRL may also act as a growth factor stimulating growth of some cancer cells. PRL first binds to its cell surface receptor, which sends a cascade of signals that are transmitted all the way into the nucleus. Then specific genes are activated that ultimately leads to cell division. Clarification of the signaling cascades may potentially identify therapeutic targets to inhibit growth of these cancers.

Dr. Mark Nachtigal's laboratory studies ovarian cancer (OvCa) which will claim the lives of approximately 1600 Canadian women this year. OvCa is the number one killer among gynecologic cancers because it is usually detected at late stages after the cancer has spread to other organs in the abdominal cavity. At late stages, OvCa is very difficult to effectively treat with the current arsenal of chemotherapeutic drugs. As well, it can quickly develop resistance to chemotherapy and then recur. All OvCa researchers are trying to identify a method to detect OvCa at early stages of the disease or to identify an effective drug or combination of drugs to treat the disease. Dr. Nachtigal's team has identified differences between OvCa cells and normal ovarian cells that will lead to a better understanding of how the disease develops and progresses. From these studies we may develop new targets for therapeutic intervention.

Dr. Gerry Johnston and Dr. Rick Singer are internationally recognized for their expertise in using yeast models to examine basic issues in cell biology. Their collaborative research program seeks to identify processes that are important to regulate the division of cells. Cancer is a disease that is characterized by abnormal regulation of cell division. For this reason, an understanding of the processes that affect cell division will provide insights into the starting point for cancer. Their research is supported by funds from the Canadian Cancer Society through grants from the National Cancer Institute of Canada, and by the Canadian Institutes of Health Research.

Dr. Ken West is also interested in understanding white blood cells, specifically a type called dendritic cells. Dendritic cells are important for activating immune responses against cancers. In order for an immune response to occur against a cancer, the dendritic cell must make contact with other white blood cells. When the two cells come together they perform a "dance" which stimulates the other white blood cells to be able to kill cancer cells. The West lab is trying to understand what makes a dendritic cell dance with a white blood cell and what proteins in the dendritic cell are responsible for the dance.

Dr. Kirill Rosen's lab is studying epithelial cells. Most major cancers are derived from these cells that line various human organs. Normal epithelial cells often form a single layer and detachment from this layer usually causes death of such cells.

Conversely, tumors typically grow as three-dimensional disorganized multicellular masses in which many cells are detached form their original location. Such cells, however, instead of dying now live and this viability is required for cancer progression. They are investigating how to reverse this resistance to death of tumor cells to cure or slow down the disease. They are particularly interested in cancer cell survival mechanisms induced by a cellular protein called Ras.

Ras is normally activated by various signals that come from outside of the cell and can, in turn, trigger events that change levels of many proteins. Certain mutations in the gene that codes for Ras can make this protein active at all times. These mutations often occur in cancer cells and the resulting Ras activity strongly contributes to the progression of many human tumors. One of the properties of Ras that is thought to make it a major factor in cancer is its ability to block death of tumor cells that grow outside of the original single epithelial layer. However, the mechanisms of this effect of Ras are not well understood and our goal is to identify these mechanisms.

Cell life and death are directly controlled by numerous proteins. They found that Ras alters levels as well as activity of some of these proteins, such as Bak, Bcl-XL, cIAP2, XIAP, Omi/HTRA2 and others. They are now investigating to what extent these changes are required for the survival of Ras oncoprotein-carrying cancer cells outside of the normal epithelial layer and for subsequent growth of Ras-driven tumors. They expect that treatment aimed at the reversal of some these changes will significantly block Ras-dependent tumor growth.

If successful, their experiments could give rise to a new type of cancer therapy based on the suppression of the survival of cancer cells within a three-dimensional tumor mass.

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