Dr. Olivier Barbier, Laval University
Pharmacological induction of hepatic glucuronidation: An efficient way to detoxify bile acids in hepatobiliary diseases.
Cholestasis, or impairment of bile flow, is one of the most devastating consequences of liver disease. Patients with this condition have extremely poor quality of life and suffer severe symptoms such as jaundice, severe itching, and fluid retention in the abdomen and legs. There are no treatments for this condition. The only cure is liver transplantation. The research project involves studying a specific metabolic detoxification pathway that eliminates bile acids through urine. The findings of this research may lead to the discovery of new treatments for cholestatic liver diseases.
Dr. Jordan Feld, University Health Network
Co-investigators: Drs. Ian McGilvray, Conrad Liles
Understanding the antiviral effects of interferon in HCV infection.
Hepatitis C is a major public health problem, affecting 200 million people worldwide, including 1-3% Canadians. Hepatitis C is a liver disease that can lead to liver failure, liver cancer and death. Although hepatitis C treatment has improved greatly, 50% of people still do not respond to current interferon-based treatment. Interferon works by activating hundreds of genes in liver cells infected with the hepatitis C virus. In many cases, these genes are able to clear the virus. To understand why interferon is not always successful in getting rid of the virus, we need to understand first how it works when it is successful. This study will focus on identifying which of the genes are necessary to clear hepatitis C infection. The research findings will lead to the development of new medications specifically targeting the antiviral genes without activating the genes that cause interferon side effects.
Dr. Kartik Jhaveri, University Health Network
Co-investigators: Drs. Sean Cleary, Sandra Fisher, Masoom Haider, Steven Gallinger
Preoperative predication of microvascular invasion in hepatocellular carcinoma by blood oxygenation level dependant magnetic resonance imaging.
Liver cancer is the fifth most common and most rapidly increasing fatal cancer in Canada. The treatment of liver cancer is complex, and cure depends on specific cancer traits, especially the spread of cancer into small blood vessels of the liver near the tumour. This spread ultimately influences patient survival. Currently this cannot be determined before treatment is undertaken. The research project will study the ability of magnetic resonance imaging (MRI) to predict such tumour spread before treatment is undertaken so that in the future the most appropriate treatment can be offered for maximum treatment benefit of the patient.
Dr. Samuel Lee, University of Calgary
Pathogenesis of cirrhotic cardiomyopathy: myosin heavy chain.
Cirrhosis due to viral hepatitis, fatty liver, autoimmune liver diseases and alcoholism is a leading cause of death and disability in Canada. Patients with cirrhosis also suffer from abnormalities of the heart. When patients with cirrhosis are put through tests to show how well the heart performs under stress, the cardiac response is blunted, suggesting the presence of a latent abnormal heart pumping function. This is known as cirrhotic cardiomyopathy (CCM). However, the underlying mechanisms remain unclear. Since the heart pumping function is impaired, it is believed that certain proteins are abnormal in CCM. This research will study if and how these proteins cause abnormal heart function. The study is significant because CCM contributes to poor outcomes for patients with cirrhosis who need liver transplantation or surgery.
Dr. Andrea Richter, Centre de recherche, Hôpital Sainte-Justine
Co-investigator: Dr. Grant Mitchell
Development of zebrafish models for North American Indian childhood cirrhosis (NAIC).
In First Nations children from Northwestern Quebec, a liver disease called North American Indian childhood cirrhosis (NAIC) is very prevalent. The only treatment available is liver transplantation. In several communities, one child out of 10 carries the gene mutation responsible for this disease. The research team identified a mutation in a protein called cirhin. The goal is to understand the function of this protein and how it causes NAIC. This research may lead to finding treatments that will eliminate the need for liver transplantation which is difficult to reconcile with traditional lifestyles in this population.
Dr. Mark Swain, University of Calgary
Regulatory role of liver recruited myeloid derived suppressor cells in response to hepatic NKT cell activation.
When the liver is exposed to hepatitis viruses, including hepatitis B and C, there is a very rapid response within the liver which is lead by a cell called the NKT cell. Activation of NKT cells in the liver results in a number of subsequent immunological events within the liver which are critical for clearing these viruses from the body. Similar events also likely occur in the early immune system response to liver cancer. However, these very early responses are hard to study in people, because patients are diagnosed with a disease long after these immune events have occurred. The research will involve studying these very early immune responses in an animal model in order to understand how they work. This will lead to the developments of new treatment for viral hepatitis.
Meghan Chow, University of Calgary (Supervisor: Dr. Mark Swain) will study the potential of probiotics in treating liver disease-related symptoms such as fatigue
Christian Parent-Robitaille, University of Montreal (Supervisor: Dr. Christopher Rose) will study whether hepatic encephalopathy (a symptom of advanced liver disease caused by a build-up of toxins in the brain) results in neurological problems post-transplant. Recipient of Doug Cassidy Summer Studentship Grant.
Alana Rose Sherker, University of Toronto (Supervisor: Dr. Jordan Feld) will research whether a particular protein manufactured by the immune system could help keep the hepatitis C virus from replicating.
Alissa Visram, University of Toronto (Supervisor: Dr. Jordan Feld) will study why all cancer patients are not screened for hepatitis B before undergoing chemotherapy.
Yirui Gui, Université de Sherbrooke
Supervisor : Subburaj IlangumaranRegulation of MET receptor signaling by SOCS1 in hepatocellular carcinoma.
Liver cancer is the third leading cause of cancer-related death worldwide. Dr. Gui is researching a gene that may help suppress tumour growth and could lead to gene-based therapies for liver cancer. Sally Yu Shi, University of Toronto Supervisor: Dr. Minna Woo The role of hepatic JAK2 in the pathogenesis of hepatocellular carcinoma. Inflammation of the liver can lead to scarring (cirrhosis) which can in turn progress to liver cancer. Dr. Shi is studying the molecular pathways in the liver that play a role in inflammation to determine how they impact the development of liver cancer.J.N. Kinola Williams, University of Alberta
Supervisor: Dr. Deborah BurshtynMarc Bilodeau, Université de Montréal
Co-applicants: R. Lapointe, F. Vandenbroucke
With the incidence of liver cancer on the rise, it is critical to find effective treatments for current and future patients. Unfortunately, it has been difficult to study liver cancer in a laboratory setting because there are no models of the disease that effectively mimic the tumours found in patients. Dr. Bilodeau and his team are using tissue from the tumours of liver cancer patients to grow copies of these tumours outside the body. Once it is confirmed that a model is similar enough to the patient’s actual tumour, doctors would be able to test a number of different treatments to determine what would work best for the patient.
Diana Mager, University of Alberta
Co-applicants: J. Yap, S. Gilmour, R. Tang-Wai, T.J. Snyder
When babies are born with liver diseases that interfere with bile flow, (these are known as ‘cholestatic’ liver diseases), their bodies are not able to process the nutrients – protein, fat, minerals and vitamins – from the food they eat. Starved of the fuel their bodies need to grow, these babies develop a form of malnutrition called ‘protein energy malnutrition’ or PEM. This malnutrition can cause serious delays in these babies achieving the same physical and cognitive milestones as their healthy counterparts.
Dr. Diana Mager and her colleagues are looking at ways to counteract PEM by boosting the amino acids that babies with biliary atresia (a form of cholestatic liver disease) receive prior to liver transplants.
Ran Chen, University of Alberta
Supervisor: Dr. Lorne Tyrrell
Hepatitis B and C are the major causes of liver cancer worldwide. Co-infection with the two diseases can lead to more rapid and aggressive liver disease. Ms. Chen is studying how both hepatitis B and C viruses respond to interferon which may help in the treatment of co-infected patients.
Ivan Diamond, The Hospital for Sick Children, University of Toronto
Supervisor: Dr. Paul Wales
Liver disease caused by parenteral nutrition (nutrition given directly into a vein) is known as Parenteral Nutrition Associated Liver Disease (PNALD). PNALD is common in infants with intestinal problems who need parenteral nutrition for a long time and it can eventually result in the need for a liver transplant. The omega-6 fatty acids (derived from soy beans) used in parenteral nutrition are believed to contribute to PNALD when used in isolation. Dr. Diamond is investigating whether omega-3 fatty acids (derived from fish oil) may be useful in preventing and treating PNALD.
Charmaine Ferguson, University of Toronto
Supervisor: Dr. Rachel F. Tyndale
Although smoking and alcohol consumption are recognized risk factors for the development of liver cancer, the reasons are not clear. Recent studies suggest that alcohol and nicotine can increase the levels of certain cancer-causing proteins in the liver. Mr. Ferguson is studying the levels of these proteins after several weeks of exposure to nicotine and alcohol to determine the impact on the liver.
Michael Ryczko, Mount Sinai Hospital University of Toronto
Supervisor: Dr. Jim Dennis
Carcinogens, viruses and obesity are well known causes of liver cancer. Cell growth depends on nutrient transporters and growth factor receptors located at the cell surface. Since the cell surface can adapt to environmental conditions, Mr. Ryczko is investigating the interplay between environmental and genetic factors in liver cancer initiation, progression and spread.
Raj Bhargava Summer Studentship Award
