Dr. Frederick Winnett Luney Graduate Scholarships and Graduate Research Awards

I work in the laboratory of Dr. Samuel Asfaha as part of the London Regional Cancer Program at Victoria Hospital. Our work is focused on identifying the role of stem cell populations in regeneration of the gut after injury, as well as in the initiation and progression of colorectal cancer. Infact, a major risk factor for colorectal cancer is Inflammatory Bowel Disease (IBD), a chronic state of colonic inflammation. The mechanism by which colitis leads to cancer, however, still remains largely unknown. Using our recently established transgenic mouse model of colitis-associated cancer, I am working to target particular pro-inflammatory pathways, both pharmacologically and genetically, in attempts to inhibit the initiation of tumorigenesis. If we can determine which inflammatory mediators are critical for cancer development, we may be able to reduce the incidence of colorectal cancer in IBD patients.

Under the supervision of Drs. Zia Khan and Christopher Howlett, my research focuses on understanding the mechanisms underlying the depletion of regenerating stem cells in diabetes.  All patients with chronic diabetes will suffer from blood vessel damage due to metabolic insults to the endothelial cells.  The defective vasculature inevitably results in various vascular diabetic complications.  Our laboratory has shown that bone marrow-resident, vessel regenerating stem cells are depleted in diabetic patients and in experimental diabetes.  This depletion is associated with changes in the cellular composition of the marrow, with enhanced adiposity and reduced osteoblast differentiation.  These studies strongly suggest that changes to the marrow cellular microenvironment lead to reduction of stem cells and impaired vascular repair.  The goal is to preserve these regenerative stem cells to prevent the development of vascular complications of diabetes.

My research focuses on Shroom3 deficiency and the effects on murine heart, kidney, and gut development. Shroom3 is a protein responsible for the regulation of apical constriction and apicobasal elongation during embryogenesis, important for the formation of tubular structures. Previous research has shown that Shroom3 contributes to neural tube closure, glomerular functioning, cardiac performance, and gut rotation. As such, the protein has been investigated in the context of many diseases including spina bifida, heterotaxy syndrome, and chronic allograft nephropathy. While several developmental abnormalities have already been associated with Shroom3 deficiency, my project aims to corroborate these findings, and discover novel abnormalities. By investigating the protein on a multi-organ, comprehensive scale, it is the hope that this approach will provide a unifying interpretation of the abnormalities and could shed additional light on systematic pathogenesis.

I am currently pursuing my PhD under the supervision of Dr. Samuel Asfaha at Victoria Hospital, where our research team is focused on identifying and targeting the cellular origin of gastrointestinal cancers. Intestinal stem cells have previously been shown to give rise to colonic and small intestinal tumors. However, the contribution of mature non-stem cells to tumor formation has recently been proposed to occur through dedifferentiation of cells upon chronic tissue injury. Therefore, I am exploring the mechanism by which colonic inflammation activates mature, quiescent tuft cells to dedifferentiate and ultimately serve as cancer-initiating cells. With this project, I aim to provide novel insight into the pathogenesis of colitis-associated colorectal cancer which will have an immediate impact in oncology and gastroenterology clinical practice.

I work with the Imaging team at Lawson Health Research Institute at St. Joseph’s hospital, where my research focus is on molecular imaging in heart disease and heart failure. Heart disease is the leading cause of mortality in Canada with 1 in 2 people touched by heart disease during their lifetime. The current methods of detection of heart disease are made through a combination of imaging methods, blood tests and clinical examination. The problem with these tests lies in the lack of disease specificity as markers in the blood can come from many tissues, and the imaging methods only detect heart disease in its late stages when you can see physical changes in the heart. My work focuses on a possible new marker, the Growth Hormone Secretagogue Receptor, as an early marker for the detection of heart disease and heart failure. I am working on detecting this marker, and associated molecular pathways, in human patient cardiac biopsies that have various forms of heart disease. I am also working on a new in vivo detection method to be able to measure this marker non-invasively in the heart.

Throughout my studies I have been able to present my work at a number of national and international conferences including the World Molecular Imaging Congress, the Canadian Cardiovascular Congress, and the Imaging Network of Ontario. These conferences showcase the newest research in both imaging methods and cardiovascular research. I have been able to showcase my new work at all these conferences in the past year with both oral and poster presentations along with highlighting my recent publications that demonstrate the new discoveries of this marker in heart disease.

I am currently pursuing my PhD under the supervision of Dr. Samuel Asfaha at Victoria Hospital, where our research team is focused on identifying and targeting the cellular origin of gastrointestinal cancers. Intestinal stem cells have previously been shown to give rise to colonic and small intestinal tumors. However, the contribution of mature non-stem cells to tumor formation has recently been proposed to occur through dedifferentiation of cells upon chronic tissue injury. Therefore, I am exploring the mechanism by which colonic inflammation activates mature, quiescent tuft cells to dedifferentiate and ultimately serve as cancer-initiating cells. With this project, I aim to provide novel insight into the pathogenesis of colitis-associated colorectal cancer which will have an immediate impact in oncology and gastroenterology clinical practice.