Dr. Jennifer EstallInstitut de recherches cliniques de Montréal (IRCM)
Role of PGC-1alpha in NAFLD-associated liver cancer
Non-alcoholic fatty liver disease affects one third of people in North America. Build-up of fat in the liver triggers inflammation and can cause permanent liver damage, increasing the risk of liver failure, diabetes, heart disease and liver cancer. It is known that diet and lifestyle, in combination with genetics, influence the development of liver cancer, but not much is known about how our genes are influenced by what we eat and whether this affects our cancer risk. Dr. Estall’s team has established that low levels of a protein called PGC-1 alpha make fatty liver disease worse. Dr. Estall will research whether the newly-discovered protective property of this protein also influences liver cancer risk associated with poor diet and obesity. This may lead to new ways to prevent liver cancer.
Dr. Denis Grant
University of Toronto
Effect of arylamine N-acetyltransferase deficiency on hepatitis B virus induced liver cancer
One of the most important risk factors for liver cancer is chronic hepatitis B. This chronic liver disease produces damage and inflammation of the liver, which in turn provides an environment that allows damaged cells to grow out of control and eventually form liver cancer. Dr. Grant’s research team has recently discovered that the removal from mice of one particular enzyme that can turn chemicals into cancer-causing agents protected them against getting liver cancer when they were exposed to a particular chemical found in cigarette smoke and some dyes. However, this protective effect was not related to the usual role of this enzyme in producing toxic by-products. Dr. Grant’s research will determine whether the elimination of this enzyme can prevent the development of liver cancer caused by the hepatitis B virus. If this is the case, Dr. Grant’s research can lead to the development of new treatments for liver cancer.
University of Alberta
Dr. Andrew Mason
Do microRNAs work in concert to modulate expression of the VEGF-A oncogene in hepatocellular carcinoma?The WHO estimates that liver cancer is the second leading cause of cancer-related deaths worldwide. Many patients cannot be treated with current available treatments and many do not qualify for liver transplantation. Therefore, other avenues for treating liver cancer are required. Dr. Mason’s laboratory has focused on identifying small regulatory molecules known as microRNAs that have been implicated in liver cancer. Their research found that the specific group of microRNAs might act together to prevent the onset of cancer by regulating a protein known as VEGF-A that promotes liver cancer growth. The research will focus on investigating whether enhancing the level of these microRNAs can inhibit the production of VEGF-A protein and as a result limit the development of liver cancer.
University of British Columbia
Drs. Orlee Guttman and Richard Schreiber
Neonatal cholestasis in British Columbia: a quality of care study.
Many babies have newborn jaundice (a yellowing of the whites of the eyes) lasting three to five days after birth because the liver is not fully developed. This type of jaundice usually clears by itself and is not a sign of liver disease. However, a small portion of newborns who have jaundice (about one in 2,500 births) have cholestasis (a condition in which bile cannot be drained from the liver). This can be a sign of serious liver disease that needs to be addressed as early as possible. In 2009, British Columbia introduced a policy that requires provincial laboratories to test bilirubin levels in jaundiced infants in order to identify those with liver disease. The goals of this research are to evaluate the laboratory compliance with this policy, to determine how many infants develop cholestasis and to assess the outcomes of these patients.
University of Toronto
Dr. Jordan FeldPoint-of-care nanodiagnostic to determine hepatitis C exposure and active infection by the naked eye.
It is estimated that 250,000 Canadians have hepatitis C and many are unaware of their infection. This is because the hepatitis C virus slowly destroys the liver, with few or no symptoms, until the disease progresses to cirrhosis (scarring of the liver) or liver cancer. Hepatitis C is the number one reason for liver transplants in Canada. Diagnosing hepatitis C is complex, requiring one test to confirm exposure to the virus, and a second to confirm the virus is still present in the blood. At this point, the genotype of the virus is also determined, which is essential to guide curative treatments. These tests are expensive and require trained personnel and sophisticated equipment. Dr. Feld is developing two novel approaches which will detect exposure to the virus, active infection, the viral genotype and the best course of treatment. These point-of-care tests have the potential to revolutionize the screening of hepatitis in community clinics and rural areas of the country, making elimination of this liver disease possible.
Dr. Gregory Steinberg
Unravelling the connections between obesity, NAFLD and metformin for the treatment of hepatocellular carcinoma.
Liver Cancer is one of the few types of cancer that affect more people today than it did 40 years ago. Patients are often diagnosed in the advanced stages of the disease with poor prognosis, with 5-year survival rates of only 20%. Metformin is the most widely prescribed diabetes medication worldwide and there is evidence that it can reduce the risk of liver cancer development in patients with diabetes. This research project will shed light on how metformin is able to reduce the risk of developing liver cancer and help physicians treat patients who are at risk of developing this deadly disease.
Bridget Anne Pierce
Dr. Kevork Peltekian
Long-term follow-up care of transplantation patients: exploring the comfort level of primary care providers in caring for patients post organ transplant.
Every year about 140 organ transplants (including liver, kidney, heart and pancreas) are performed at the Multi-Organ Transplant Program in Halifax which serves patients living in Atlantic Canada. Many of the transplant patients come from rural communities and their follow-up care is shared between the transplant team and the primary care physician. Until now, there has been no research looking at the comfort levels of primary care physicians in providing post-transplantation care. This research project aims to uncover how comfortable physicians are in providing post-liver transplantation care through the use of an online questionnaire survey. The findings of this study may be used to identify areas of improvement for managing the care of post-transplant patients.
Université de Montréal
Supervisor: Dr. Christopher Rose
Project Title:Tyrosine: a new pathogenic factor involved in the pathogenesis of hepatic encephalopathy?
Tyrosinemia is a genetic inborn error of metabolism associated with severe liver disease in infancy. About one person in 100,000 is affected with tyrosinemia globally. However, the disease is particularly common in the region of Saguenay-Lac-St-Jean, Quebec where one person in 20 is a carrier of the defective gene, and one person in 1,846 is affected with the actual disease. It is believed that increased tyrosine metabolism leads to brain toxicity called hepatic encephalopathy (HE). The goal of this study is to identify the metabolites responsible for this condition. The results of this study will define the role of tyrosine and its metabolites in the development of HE. As well, research findings will lead to a better understanding of the neurologic disease observed in children born with tyrosinemia.
University of Calgary
Supervisor: Dr. Carla Coffin
Project Title:Differences in immune cell subpopulation infection in hepatitis B virus (HBV) monoinfected versus human immunodeficiency virus type-1 (HIV-1) and HBV coinfected patients.
Hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) are leading causes of death worldwide. Chronic hepatitis B infection is common in HIV-1 infected individuals because these two viruses are transmitted in similar ways. Although the development of effective treatments has decreased the progression of HIV, for unknown reasons complications of liver disease are much more prevalent in coinfected individuals. The purpose of the study is to determine whether specific immune cells are targeted by viruses in hepatitis B monoinfected patients as compared to the hepatitis B/HIV-1 coinfected patients. The project will contribute to the understanding of the role these viruses play in disease progression and why they cannot be eliminated from the body. The study may have impact on future therapies that will lead to eradication of both viruses.
Jason Alexander Ji-Xhin Wong
University of Alberta
Supervisor: Dr. Michael Houghton
Project Title:Characterization of broadly cross-neutralizing antibodies elicited by a recombinant hepatitis C virus gpE1/E2 vaccine candidate in a phase 1 clinical trial.
It is estimated that 170 million people worldwide have hepatitis C and several million new infections occur every year. There is an urgent need for a vaccine against the hepatitis C virus. There is evidence that both neutralizing antibodies and cellular immune responses targeting the virus play a role in viral clearance. An ideal vaccine will be able to induce both type of immune response. Dr. Houghton’s research has lead to the discovery of a vaccine candidate that has been tested in a clinical phase 1 trial. Further research is required to determine which antibodies bind to the surface of the virus and how they prevent or limit the infection process. Research findings will help in designing the optimal vaccine against this major disease.
Laura Michelle Zenith
University of Alberta
Supervisor: Dr. Puneeta Tandon
Project Title:The efficacy and safety of an aerobic exercise intervention in decompensated cirrhosis.All forms of liver disease can lead to cirrhosis. Among many other complications, patients with cirrhosis suffer muscle waste. As a result, they tire more easily when performing daily activities, have reduced quality of life and higher risk of death. It has been proven that regular exercise (e.g. walking, riding a bike) decreases fatigue. A randomized trial evaluating the effects of exercise in early cirrhosis has almost been completed by Dr. Tandon’s team. As a next step, they would like to investigate the impact of exercise in patients with more advanced cirrhosis. This is extremely important as majority of patients on the liver transplant list have advanced cirrhosis. The research will compare patients on exercise regimen to those on usual care and measure the effects of exercise on heart and lung function, muscle mass, quality of life and safety. The findings of this study may lead to improved quality of life for all patients suffering from end-stage liver disease.
Mount Sinai Hospital
Supervisor: Dr. Jim Woodgett
Project Title:A developmental pathway perspective to liver cancer: The role of GSK-3 α and β genes.
Liver cancer rates are on the rise in Canada. About 70% of patients with liver cancer that undergo treatment experience recurrence of the cancer within 5 years. The development and recurrence of liver cancers have been demonstrated to be linked to stem-cell like cells. Dr. Woodgett’s team has generated a clinically relevant and novel model to understand these cells by utilizing a genetic approach that deletes certain gene mutations that is found in one third of liver cancers. This model has tremendous implications for the development of better therapies that may prevent recurrence of cancerous cells and their spread.
Supervisor: Dr. Peter Metrakos
Project Title: Lipid droplets and associated proteins in hepatocellular carcinoma tumour cells.The incidence of liver cancer has been steadily increasing alongside rising incidences of viral hepatitis and obesity in Canada. Very few liver cancer studies have focused on fat metabolism, which may play an important role in the development and progression of liver cancer as well as many other cancers. Fat metabolism in the body is regulated in part by specialized structures within cells called lipid droplets (LDs). Ms. Yassa will research LDs and other important proteins surrounding and regulating the LDs to determine what role they play in the development and progression of liver cancer. The findings of this research may lead to the development of new treatments for liver cancer.
University of Toronto
Supervisor: Dr. Johane Allard
Project Title:Regulation of hepatic gene expression in patients with non-alcoholic fatty liver disease compared to healthy controls.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Canada. NAFLD can lead to liver cirrhosis and liver cancer as well as other health problems including diabetes and heart disease. Mechanisms that regulate our genes could play a role in the development of fatty liver disease. It has been established that genes that lead to more fat storage are activated in patients who have NAFLD compared to healthy people. In this project, data collected from patients with NAFLD and healthy controls will be compared and analyzed to identify which genes are likely to be involved in the development of NAFLD. The overall goal is to determine if gene regulation is a mechanism that contributes to fatty liver. These genes could be new targets for prevention and development of treatment of NAFLD.
Supervisor: Dr. Olivier Barbier
Project Title:Is there a place for n-3 polyunsaturated fatty acids in the anti-cholestatic pharmacopeia of hepatobiliary diseases: a preclinical and pharmacological investigation.
Impaired bile flow (cholestasis) is one of the most devastating manifestations of liver disease. While liver diseases that involve impaired bile flow are among the leading indications for liver transplantation in all age groups, no curative treatment has been identified. Therefore, novel treatment approaches are needed for an efficient treatment of diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). It has recently been observed that Omega 3 fatty acids can be used to detoxify the liver from bile acids which accumulate in the liver, killing liver cells and causing liver damage. Research will determine whether Omega 3 fatty acids can be useful for protecting liver cells from damage and whether this may have a potential for the treatment of these liver diseases.
Supervisor: Dr. Gregory Steinberg
Project Title:Treating non alcoholic fatty liver disease by activating the AMP-activated Protein Kinase (AMPK).
Non-alcoholic fatty liver disease (NAFLD) is a very common condition affecting almost 1 in 4 individuals and is tightly linked to the obesity epidemic. NAFLD can lead to health problems including diabetes and heart disease, and affected individuals may require a liver transplant if not cured. Fat metabolism in the liver is being regulated by a specific protein. The student will be testing whether a commonly used drug for the treatment of arthritis might be effective in reversing fatty liver disease and identify how this occurs. The findings of this research will lead to new therapies for treating this very common liver disease which currently has no cure.
Université de Montréal
Supervisor: Dr. Fernando Alvarez
Project Title:Hepatitis E virus: an emerging chronic infection in liver-transplant and immunosuppressed patients.
All liver transplant patients have to take immunosuppressive drugs to prevent rejection of their new organs. These patients are more vulnerable to infections. Some viruses present in our environment are harmless in healthy individuals but can be life threatening for immunosuppressed patients. Hepatitis E Virus (HEV), which is common in developing countries with suboptimal sanitary conditions, is also highly prevalent in livestock in Canada. Recently we reported a high prevalence of HEV infection in children who had received a liver transplant. Some patients developed chronic liver disease and cirrhosis. The goal of this project is to develop better diagnostic tools to detect this virus and to understand the impact of HEV in children. This project could lead to new recommendations for prevention of infections in children who undergo liver transplantation.
University of Alberta
Supervisor: Dr. Diana Mager
Project Title:How do high intakes of fructose and glycemic index influence markers of inflammation, liver function and lipoprotein expression in children and adolescents with non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) typically occurs in children who are overweight or obese. It is not well understood why some children develop fat in the liver and others do not. Dr. Mager’s research has shown that fat build-up in the liver may be related the foods that are high in added simple sugars such as high corn syrup fructose (HCFS) that children commonly eat. The student will study how intake of foods high in HCFS and saturated fats can influence liver function, inflammation of the liver and levels of lipid and lipoproteins in children with NAFLD. This information will lead to the development of better treatment strategies for children with NAFLD.
Dr. Fernando Alvarez
CHU Sainte-Justine Montreal, Quebec
Project Title:Depletion of B cells as a treatment for autoimmune hepatitis
Autoimmune hepatitis (AIH) is a liver disease caused by the body’s own immune system which attacks the liver resulting in inflammation and scarring. If left untreated, AIH is always fatal. AIH may present both as an aggressive form of acute hepatitis or a chronic illness that can progress to cirrhosis. Recently, Dr. Alvarez and his team have discovered that a complete remission of AIH could be achieved in some patients with an antibody (Rituximab) that temporarily destroys a type of white blood cells called B-lymphocytes. However, AIH is believed to be caused by the attack on the liver by T-lymphocytes and not by B-lymphocytes. The goal of this research is to explain the mechanisms by which destruction of B-cells help in the control of the AIH. The research findings may lead to new treatments for AIH, with fewer side effects than what is reported with current available therapy.
Dr. Klaus Gutfreund
Co-Applicant: Dr. Lorne Tyrrell
University of Alberta Edmonton, Alberta
Project Title: Identification and targeting of inhibitory T-cell signaling pathways in the duck hepatitis B model to explore novel immunotherapeutic strategies for chronic hepatitis B.
Chronic hepatitis B affects over 350 million people worldwide and an estimated 300,000 people in Canada. Many patients with chronic hepatitis B will die due to cirrhosis and liver cancer. Current treatments with interferon alpha and oral antiviral drugs effectively suppress the virus but most patients will not maintain a long-term response to therapy. Hence, a prolonged antiviral therapy is often required which is costly and many patients eventually develop drug resistance. Therefore, finding better treatments for hepatitis B remains a priority. The purpose of this research is to develop new treatment strategies that stimulate a successful immune response to resolve chronic hepatitis B infection. Dr. Gutfreund’s team has recently developed novel genetic vaccines and identified several molecules that can be targeted to improve antiviral immune responses. The focus of this research is to further explore these promising new therapeutic vaccines, which will lead to the development of new treatments for hepatitis B patients.
Dr. Mathieu Laplante
Quebec City, Quebec
Project Title: Determination of the role of Deptor in the development of liver cancer.
Liver cancer is one of the most common cancers worldwide. Liver cancer is resistant to both conventional chemotherapy and radiation. This leaves liver cancer patients with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools to treat this disease is needed. A protein called mTOR is known to be commonly overactivated in cancer. This protein contributes to cancer growth by promoting protein and lipid synthesis. Recently, Dr. Laplante has identified a new protein called Deptor that can inhibit mTOR. Deptor levels are low in liver cancer cells and preliminary experiments indicate that Deptor loss promotes tumour formation. The objectives of this research are to find out the role of this protein in liver cancer and to determine whether it could be targeted for the development of new treatment of liver cancer.
Dr. Andrew MasonUniversity of Alberta Edmonton, Alberta
Project Title: Mouse models of genetic and environmental factors in primary biliary cirrhosis.
It is believed that primary biliary cirrhosis (PBC) results from an abnormal reaction of the body’s immune system possibly initiated by an infection. Designed to protect the body from infection, the immune system of PBC patients attacks the liver causing slow, progressive damage to the bile ducts. When the bile ducts are damaged, bile and other substances cannot be eliminated and accumulate in the liver. This eventually leads to cirrhosis. It is believed that both genetic and environmental factors may play a role in the development of PBC. Dr. Mason has recently discovered that a virus found in PBC patients resembles a mouse virus known as mouse mammary tumour virus. A mouse model has recently been developed. This model has the same immune features that have been found in patients with PBC. Dr. Mason has discovered that mouse mammary tumour virus is associated with the development of autoimmune biliary disease (similar to PBC) in these mice. Furthermore, Dr. Mason has discovered that this biliary disease can be blocked by antiviral therapy. This research should lead to the development of treatments for patients with PBC.
Dr. Christopher Richardson
Co-applicant: Dr. Eric Arts
Dalhousie University Halifax, Nova Scotia
Project Title: Development of a novel hepatitis C virus cloning system in yeast to screen for infectious genomes and determine the role of neutralizing antibodies in viral clearance at acute infection.
Hepatitis C virus is responsible for 170 million infections worldwide and is a major cause of cirrhosis and liver cancer. However, 30% of those infected with the hepatitis C virus never develop chronic disease and get rid of the virus during the acute stage of the infection. Dr. Richardson’s research team proposes that the virus clearance is related to the rapid development of antibodies that neutralize the specific hepatitis C strains infecting the patients. This research requires the development of a unique yeast-based cloning system to produce infectious virus based on specific proteins derived from recently infected patients that either get rid of the infection of go on to develop chronic disease. Findings of this research will lead to the development of more effective treatments of chronic hepatitis C.
Dr. Naglaa Shoukry
Centre de Recherche du CHUM (Hôpital St-Luc) Montréal, Quebec
Project Title: How does IL-28B polymorphism influence the outcome of acute hepatitis C?
Chronic hepatitis C is a major cause of liver disease and liver cancer. We still do not understand how a small fraction of people exposed to the virus can get rid of it while the rest cannot. Recent studies have established a correlation between the variations in one gene known as IL-28B and the capacity to eliminate hepatitis C infection. However, how this gene variation influences the immune response against the virus is not yet known. Dr. Shoukry believes that this gene controls the type of immune response that develops upon infection where patients who have the bad gene variant are not able to respond and consequently cannot clear the infection. The research findings will lead to the development of new treatments for hepatitis C.
Mr. Andrew Collins
Supervisor: Dr. Gregory SteinbergProject title: Treating Non Alcoholic Fatty Liver Disease by Activating the AMP-activated Protein Kinase
Non-alcoholic fatty liver disease (NAFLD) is a common condition. The growing incidence of NAFLD is tightly linked to the obesity epidemic. NAFLD can also lead to other health problems including diabetes and heart disease, and affected individuals may require a liver transplant if inflammation and liver damage develop. The number of people who develop severe liver damage is likely to increase further as the rate of childhood obesity becomes more prevalent. Fat metabolism in the liver is being regulated by an enzyme that is switched on by exercise and drugs such as metformin and aspirin. Mr. Collins will be testing whether metformin and aspirin might be effective in reversing NAFLD. The findings of this research will lead to new therapies for treating this very common liver disease which currently has no cure.
Ms. Emma Torbicki
The Hospital for Sick Children
Supervisor: Dr. Nicola Jones
Project Title: Investigating the Role of Autophagy in Ischemia Reperfusion Injury.
Currently, the short-term outcome after pediatric liver transplantation is excellent. However, the long-term outcomes for children who require liver transplantation need to be improved. During a transplant, when the liver is taken from the donor, the blood flow is cut off causing lack of oxygen. Once the organ is placed in the patient and the blood vessels reconnected, the organ receives blood once again. This results in tissue damage due to the formation of toxins and invasion by white blood cells. Recent studies indicate that a specific cellular recycling pathway called autophagy may help to remove the toxins and limit inflammation due to immune response. The results of this study will be the first step in determining if autophagy is protective in this injury that occurs in transplanted livers.
Ms. Elizabeth Kuczynski
Sunnybrook Health Sciences Centre
Supervisor: Dr. Robert Kerbel
Project Title: Reversible Resistance to Sorafenib in Hepatocellular carcinoma (HCC): Mechanisms and Implications.
Worldwide, liver cancer is the third most common cause of cancer-related deaths. Sorafenib is a drug that targets blood vessels that supply tumour with blood. However, eventually patients stop responding to drug treatment and develop resistance. Ms. Kuczynski is studying how, contrary to common perception, resistance may be reversible and not permanent. By giving a prolonged time off a drug, cancer cells can be “reset” and re-sensitized to once again respond to therapy. This research may have important implications for the clinical management of liver cancer and potentially other cancer-drug combinations in which resistance may be reversible.
Mr. Daniel Pang
University of Alberta
Supervisor: Dr. Lorne Tyrrell
Project Title: Studying Hepatitis A Virus (HAV) Infection, Replication and Clearance in a Chimeric Mouse Model.
Hepatitis A virus (HAV) and hepatitis C virus (HCV) are two similar viruses that cause liver disease in humans. However, HAV primarily causes short-term disease while HCV usually causes long lasting disease for reasons that are not fully understood. While a better comparison of these two infections is needed, there is currently no small animal model to study HAV. Dr. Tyrrell’s lab has developed a mouse model with mixed human/mouse livers that are susceptible to HCV infections. The purpose of the study will be to test the model’s susceptibility to HAV infection and to analyze its ability to fight off infections. Mr. Pang will investigate whether the early immune response is sufficient to eliminate HAV in the mouse model. A better understanding of how we fight off HAV and HCV infections may help in the development of a preventative vaccine for hepatitis C, one of the leading causes of liver cancer.
Ms. Mandana Rahbari
University of Alberta
Supervisors: Drs. Andre Mason and Michael Houghton
Project Title: Virological Footprint of T-cell Responses in Patients with Primary Biliary Cirrhosis.
Primary biliary cirrhosis (PBC) is known as a cholestatic liver disease because it blocks or stops the flow of bile. Although PBC is a disease of unknown cause, both genetic and environmental factors may influence the development of PBC. The objective of this research is to explain the relationship between an infection with the human betaretrovirus and PBC and see if the infection with this virus plays a role in the development of PBC. This knowledge could be used to design drugs to treat PBC.
Dr. Olivier Barbier
Project Title: 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
Project Title: 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
Project Title: 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
Project Title: 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
Project Title: 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
Project Title: 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
Michael Doré Nguyen, CHU Sainte-Justine, Montréal (Supervisor : Dr. Fernando Alvarez) will research the risks of viral infections for children who have received liver transplants and are taking immuno-suppressive drugs.
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.
Université de Sherbrooke
Supervisor: Subburaj Ilangumaran
Project Title:Regulation 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
Project Title: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 Burshtyn
Project Title: Hepatitis C virus (HCV) regulation of the major histocompatibility complex class I (MHC I) and natural killer (NK) cell recognition.
Most patients with an acute hepatitis C infection do not develop symptoms but a large percentage will go on to develop chronic hepatitis C. Dr. Williams is researching how natural killer cells (part of the immune system’s response to attacks by viruses) respond to the hepatitis C virus and how they work with certain molecules to help clear the hepatitis C virus.
Marc 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.
Simon Bow, University of Alberta
Supervisor: Dr. Jason Yap
Viral hepatitis can cause cirrhosis and liver cancer in adults which is why routine screening of high risk groups is recommended. Currently, there are no guidelines for liver cancer screening of children with chronic viral hepatitis. Under the supervision of Dr. Yap, Mr. Bow reviewed the medical records of children with chronic viral hepatitis to determine if ultrasound screening would provide valuable information that could be used in the care of these patients.