The University of Guelph hosts a number of innovative cancer researchers in the basic, social, and medical sciences. This past summer the University launched the Institute for Comparative Cancer Investigation, which will bring together these researchers and will enable the researchers to study cancer in animals as well as humans. Brief profiles of a few of these researchers are listed below.

Brenda Coomber, Professor, Dept. of Biomedical Sciences
Dr. Coomber's research group has been investigating aspects of cancer biology at the University of Guelph for over 16 years. The main current projects in the laboratory are:

1) We are investigating aspects of tumor microenvironment (especially ischemia) and how it contributes to cancer progression by affecting the development of DNA mutations and alterations in epigenetic control. Areas of poorly perfused tissue are commonly found in all solid tumors, yet the cancer cells located here are not
necessarily dead and dying. A better understanding of the adaptive changes that cancer cells use to survive and thrive under these conditions will help us improve the our therapeutic approaches for dealing with this disease. This work is primarily focussing on colorectal carcinoma, and is currently funded by the Canadian Cancer Society, and the Cancer Research Society

2) We are examining the phenotype of tumor blood vessels and determining how this varies with different types of cancers and with different stages of tumor progression. It has long been known that blood vessels in cancers are quite different from those of surrounding normal tissue, but we have also discovered a variety of differences in the blood vessel makeup that seem to be related to specific cancer types. We have recently shown with some experimental systems that the blood vessel characteristics may significantly impact tumor responses to anti-angiogenic therapy. This work is currently focussing on malignant melanoma, colorectal carcinoma, and breast cancer, and is funded by the CIHR.

3) We are discovering pathways used by cancer cells to avoid apoptosis in non-adhesive environments. When cancer cells break away from their tumor and spread in the circulation to distant sites, they must survive varying periods of suspension / non-adhesion (in the blood, at their new home, etc.) before they can form a metastatic colony. This is particularly true for ovarian carcinoma, where numerous cells are shed into the pelvic cavity to eventually seed new tumors on the visceral surfaces of other organs. Identifying the pathways that cancer cells use for this unusual form of survival will help us develop therapies to more specifically target these spreading cells. This work is currently focussing on colorectal and ovarian carcinoma and is supported by the CIHR.

Alison Duncan, Associate Professor, Dept. of Human Health and Nutritional Sciences
My general research interest relates to the biological effects of functional foods and nutraceuticals on chronic disease-related endpoints through human intervention studies. My specific interest involves the role of soy and its constituent protein and isoflavones in the reduction of disease risk, including cardiovascular disease, diabetes, breast cancer, prostate cancer and kidney disease. Another research interest in relation to nutraceuticals involves the use of natural health products (prevalence, associated attitudes and beliefs) in healthy and clinical populations. My specific research activity in the area of cancer has been to study the role that consumption of soy protein and its components can play in reducing risk of prostate cancer; this research was funded by the American Institute for Cancer Research. I have also completed research that has explored the use of antioxidant supplements in women undergoing chemotherapy for breast cancer.

James Kirkland, Associate Professor, Dept. of Human Health and Nutritional Sciences
Niacin is a B vitamin that is involved in energy metabolism, but it also plays key roles in DNA repair and in signal transduction. Poly(ADP-ribose) is synthesized on proteins in response to DNA damage, using nicotinamide adenine dinucleotide (NAD) as substrate. Poly(ADP-ribose) synthesis is important in DNA repair and we are testing the effect of niacin deficiency on poly(ADP-ribose) synthesis, DNA repair rates, apoptosis and the progression of leukemia in response to carcinogen exposure. NAD and nicotinic acid are also used to make cyclic ADP-ribose and NAADP, two molecules that control the release of calcium from intracellular stores. Calcium release controls many aspects of cell signaling, and we are interested in the processes of long term depression and potentiation that occur in brain neurons during the development of memory and learning. We are testing the effect of niacin deficiency and pharmacological supplementation on maze learning and brain metabolism. This research has been funded by the NCIC, the Cancer Research Society, and NSERC.

Roger Moorehead, Associate Professor, Dept. of Biomedical Sciences
The type I insulin-like growth factor receptor (IGF-IR) is a protein that plays an important role in a number of human cancers. Although elevated IGF-IR levels and activity have been found in breast cancer, high breast tumor IGF-IR levels have been associated with both enhanced and reduced disease-free survival. Therefore, the exact function of IGF-IR in human breast cancer remains unclear. My lab has genetically altered mice to express high levels of IGF-IR in the mouse mammary gland. Our work has shown that elevated levels of IGF-IR rapidly induced mammary tumor development. There are however still a number of unanswered question regarding IGF-IR's role in breast cancer such as (i) is there stage in mammary development (i.e. puberty) where the mammary gland is more susceptible to tumor development induced by IGF-IR, (ii) how exactly does IGF-IR transform a normal cell into a tumor cell, (iii) do tumors initiated by IGF-IR progress and eventually metastasize to other tissues, and (iv) if the IGF-IR is targeted with a drug will tumors shrink and if so will they permanently disappear or eventually recur. The researching ongoing in my lab will address these questions and direct future research examining IGF-IR as a screening tool or as a therapeutic target.

Jim Petrik, Associate Professor, Dept. of Biomedical Sciences
Ovarian cancer is a very difficult disease to deal with because the signs are often very vague and therefore isn’t typically discovered until the later stages. One of the reasons that the disease is not well understood is the lack of a good animal model with which to study ovarian cancer. We recently have developed an animal model that very closely replicates the human disease, providing us with a tool to make some very important discoveries in the biology and treatment of ovarian cancer. We currently are looking at techniques to starve ovarian tumours of their blood supply. Adequate blood supply is a requirement for the formation and growth of ovarian tumours and we hypothesize that if we prevent these new blood vessels from forming, we can shrink the tumours. We also are working on discovering new markers of the disease that will allow us to detect ovarian tumour at their very early stage when they can be treated very successfully. The result obtained in our laboratory will hopefully allow us to provide early detection and successful treatment of ovarian cancer.

Frances Sharom, Associate Professor, Dept. of Molecular and Cellular Biology
Professor Frances Sharom’s research interests lie in the area of membrane proteins and their role in health and disease. One of her current projects is to investigate a transporter molecule called P-glycoprotein, which sits within the cell membrane and acts as an ATP-driven efflux pump. This molecule pumps chemotherapy drugs out of cells, allowing cancer cells to develop resistance to multiple drugs. Professor Sharom and her team are using fluorescence techniques to determine the binding and transport mechanism of P-glycoprotein. They hope to understand how the protein can bind to so many different drugs, and to determine the mechanism of its pumping action. This research is crucial in the development of “modulator drugs” which could be administered together with chemotherapy to prevent the action of P-glycoprotein and the drug resistance it causes.