Metabolism is tightly regulated in our body, as shortage or overabundance of some components can affect our health. Pioneering work by LDI researchers established that alterations in iron metabolism are linked to cancer growth (Prem Ponka) and to neurodegenerative diseases such as Alzheimer’s (Hyman Schipper). The researchers developed a blood test to look at markers of iron metabolism that can help to identify patients suffering from dementia at very early stages. This is important because it is easier to help patients with dementia in early stages of the disease and most of the tests available can only detect the disease at later stages. These findings are helping in the search for treatments by modulating iron metabolism, to improve the efficacy of anticancer treatments and to slow down the development of dementia (Prem Ponka):
The metabolism of cancer cells is different from that of normal cells and LDI researchers discovered that metformin (Michael Pollak), a classic drug used in the treatment of diabetes has, as well, anticancer properties by interfering with metabolic dependencies of cancer cells:
In addition, LDI researchers discovered that the blood levels of a hormone called insulin like growth factor can help to predict the chances of developing prostate, breast, and colorectal cancers (Michael Pollak):
Various diseases occur because of disturbances in the function of our genes. Often, these malfunctions arise from errors in the genes (mutations) or by alteration of epigenetic mechanism that our body uses to turn on and off genes. LDI researchers discovered that if an epigenetic modification called arginine methylation occurs in excess, it could favor cancer growth and the development of neurodegenerative diseases (Stephane Richard). These ground-breaking discoveries led to the development of a blood test to measure how much arginine methylation is going on in our body (Stephane Richard) and suggests that inhibitors of arginine methylation (Stephane Richard) can help to fight several multiple scleroses and several types of solid tumors such as breast, colon, glioma, and non-Hodgkin’s lymphoma.
To fight infections, we need to understand how viruses and bacteria attack our body and how our body fights back against them. This knowledge, which is necessary to develop effective interventions, has led to the development of antibiotics, vaccines, and targeted therapies. LDI scientists have made major contributions to the understanding of how interferon helps our body to fight viral infections (James Hiscott, Rongtuan Lin and Chen Liang). Interferon is an important component of our first line of defense (innate immune response) against a variety of viral infections such as hepatitis C, influenza, and HIV.
LDI researchers discovered that a component of the innate immune response against viral infections called OAS1 helps our body to fight Covid 19. They also identified drugs that by activating OAS1 could help Covid19 patients, which have low OAS1 activity. In collaboration with researchers around the world, LDI researchers discovered that a variant of the gene OAS1 that protect us from getting very sick with Covid 19 (Brent Richards).
An intensive area of research in the field of infectious diseases is aimed at understanding how bacteria and viruses can overcome and evade our immune response and therapeutic interventions. Breakthrough discoveries by LDI scientists working on HIV, which continues to this day (Chen Liang), include pioneering investigations to understand how the HIV virus evades drug treatments (Mark Wainberg). LDI researchers contributed to the development of the first effective drug to treat the disease, Lamivudine, which is part of an AIDS cocktail of drugs still used to this day and discovered that resistance to Lamivudine is driven by HIV mutations in a protein of the HIV virus, called polymerase (Mark Wainberg).
Various diseases occur because of disturbances in the function of our genes due to errors in them (mutations). We inherit some of these mutations from our parents while others accumulate during our lifetime. Identification and study of these mutations is very important because it enables the establishment of screening programs to identify and advise patients with elevated chances of developing certain types of cancer. Often mutations work as biomarkers (or molecular tags) that can sometimes guide physicians in their choice of effective treatments. This type of study requires the analysis of large amounts of data, the development of reliable tests and the collaboration of researchers with many different areas of expertise. LDI scientists are known for this type of collaborative expertise and are recognized worldwide for their contribution to deciphering the role(s) of two genes called Breast Cancer Gene 1 (BRCA1) and Breast Cancer Gene 2 (BCRA2). BRCA1 or BRCA2 mutations significantly increase the chances of developing aggressive cancers. Specifically, LDI researchers are acknowledged for discovering BRCA mutations that are unique to Ashkenazi Jewish and Canadians of French descent and for deciphering patterns of biomarkers in BRCA1 breast cancer that can guide physicians to treat patients with these mutations (William Foulkes).
Epidemiologists collect and analyze data to investigate health issues. Epidemiologists are key to guiding the development of methods to collect and analyze all kinds of clinical data, from behavioral to infectious diseases. By applying these methods, epidemiologists can assess the impact of health intervention, the impact of lifestyle changes in our health and discover why some people are more susceptible to catch certain diseases. For example, by analyzing clinical databases with information from thousands of patients being followed at the JGH and other hospitals in nine countries, LDI epidemiologists discovered that COVID-19 patients younger than 60 years old with a specific OAS1 gene variant are at a higher risk of developing severe respiratory failure, venous blood clots or liver damage (Brent Richards).
Other internationally recognized clinical studies by LDI epidemiologists include the discoveries that abnormal Vitamin D levels are associated with the development of multiple sclerosis, obesity, and other diseases (Brent Richards, John Hoffer); and the uncovering of genetic variations that protect from osteoporosis (Brent Richards and Celia Greenwood).
LDI epidemiologists are known for their expertise in the creation of questionnaires to detect patients affected by mental health problems. A now classic test utilized all over the world is the Montreal Cognitive Assessment (MoCA) test, developed by LDI researchers for early detection of dementias (Howard Chertkow). The MoCA test is utilized worldwide because it can distinguish if weaker memory is an early sign of Alzheimer’s disease or other dementias, normal aging or subtle cognitive impairment that happen in patients affected by Parkinson’s disease, vascular cognitive impairment, Huntington’s disease, brain metastasis or primary brain tumors, sleep disorder, multiple sclerosis, traumatic brain injury, depression, and heart failure.
By analyzing hundreds of published studies using different tests used to screen and diagnose depression, LDI scientists discovered that a worldwide use test, the PHQ-9 is good for depression screening but not for diagnosis (Brett Thombs).
Using state of the art approaches and mouse models, LDI scientists are paving the way for testing and development of innovative therapies:
Developing new approaches for a better comprehension of how some aggressive pediatric brain tumors arise (Claudia Kleinman)
Finding a driver of aggressive adult brain tumors (Arezu Jahani-Asl)
Building mouse models of human disease led to the discovery of new drugs to fight Alzheimer’s disease (Andréa LeBlanc)
Discovering new targets to fight prostate, brain, and skin cancers (Antonis Koromilas)
Reversing Multiple Sclerosis using an immune-suppressing treatment (Jacques Galipeau)
Finding biomarkers to develop a blood test for early detection of Alzheimer’s Disease (Hyman Schipper)
Singling out and targeting unique mechanisms of chemoresistant in Triple Negative Breast Cancer (Mark Basik)
Baldness Gene Discovered: 1 In 7 Men at Risk (Brent Richards)
Repurposing of Ribavirin, an antiviral drug to fight leukemia (AML) (Sarit Assouline)
COVID-19 prenatal stress on mother and child could have lasting impact (Ashley Wazana)
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