Three of Canada’s leading researchers in brain health, heart health and cancer have been singled out by the University of British Columbia Faculty of Medicine for their accomplishments, and for their potential to make further contributions in their fields.
The sixth annual Margolese National Brain Disorders Prize will be given to Michael Meaney of McGill University, who has explored how epigenetic changes affect neurodevelopment. The Margolese National Heart Disorders Prize will be bestowed on Ernesto Schiffrin, also of McGill, who has advanced understanding of high blood pressure’s effects on vasculature. The third annual Dr. Chew Wei Memorial Prize in Cancer Research will be awarded to Connie Eaves, of UBC and the BC Cancer Agency, who has made seminal contributions to understanding stem cell systems in the blood and mammary gland.
All three prizes include a $50,000 award, making them among the most lucrative honours given by a Canadian university. The recipients were chosen by an international panel of experts and a UBC committee chaired by Robert McMaster, Executive Associate Dean, Research and Deborah Money, Executive Vice Dean.
The Margolese prizes were created by an estate gift to UBC by Leonard Herbert Margolese to recognize Canadians who have made outstanding contributions to the treatment, amelioration or cure of brain or heart disorders. Margolese, who died in 2000, was a Vancouver businessman who had a heart condition and whose brother had Alzheimer’s disease.
The Dr. Chew Wei Memorial Prize in Cancer Research is named for a Hong Kong physician who retired to Vancouver in 1988. An obstetrician and gynecologist, Dr. Wei grew determined to improve outcomes for people with cancer. After his death in 2009, his family and friends sought to honour his goals by donating $4.5 million to the Faculty of Medicine for a prize in cancer research and a professorship in gynecologic oncology.
Michael Meaney, a James McGill Professor in the Departments of Psychiatry and Neurology & Neurosurgery at McGill University, is credited with launching the fusion of epigenetics and neuroscience. His highly original and innovative research used rodent models to measure how variations in early social conditions, especially maternal care, led to changes in the transcription of specific genes that regulate adult stress responses and synaptic plasticity. Subsequent studies identified key differences in DNA methylation in the promotor region for these same genes, and also showed that reversal of the epigenetic state reversed the changes in gene transcription and stress responses. The resulting paper, published in Nature Neuroscience, has become the most highly-cited paper in that journal. “Neuroepigenetics” is now one of the fastest-growing fields in neuroscience.
Working with post-mortem human brain tissue, Dr. Meaney and his collaborators have shown that the DNA methylation status of a set of genes first identified in rodents were similarly methylated in humans as a function of adverse childhood experience – essentially revealing a molecular imprint from childhood mistreatment. His lab is now pursuing next-generation sequencing analysis that will define epigenetic states across the genome in relation to environmental conditions in early life.
“These studies provided a biological framework for our understanding of the interaction between the forces of ‘nature’ and ‘nurture,’” wrote Eric Kandel, a Professor in the Department of Neuroscience at Columbia University, adding that Dr. Meaney’s work has “profound implications for public health policy.”
With funding from Brain Canada, Dr. Meaney created the Canadian Neuroepigenetic Network, linking researchers at several Canadian universities, to focus on translating studies of the epigenome into clinical practice and prevention/intervention programs. He leads the development of integrative neuroscience as Associate Director of the Singapore Institute for Clinical Sciences, where he is overseeing a birth cohort study that will track epigenomic variations in relation to neurodevelopmental outcomes. He also is the Scientific Co-Director of the Ludmer Centre for Neuroinformatics and Mental Health at McGill University, which aims to provide the computational resources to better understand the biological basis for vulnerability to mental disorders and provide an empirical basis for diagnosis and expected treatment outcomes.
Recognized by the Institute for Scientific Information as a “most highly-cited scientist” in the area of neuroscience, Dr. Meaney received the Kerman Award from Cornell University, the Klaus J. Jacobs Research Prize from the Jacobs Foundation, the Distinguished Investigator Award from the Brain & Behavior Research Foundation, and was honoured as a Presidential Scholar by the University of California, San Francisco.
Ernesto Schiffrin, a Professor and Vice-Chair, Research, in the Department of Medicine at McGill University, has advanced understanding of vascular remodeling in high blood pressure.
Dr. Schiffrin discovered the remodeling mechanisms of small resistance arteries and the effects of anti-hypertensive therapy on vascular remodeling in humans. He was the first to demonstrate the role of endothelin in high blood pressure, specifically in salt-sensitive and severe hypertension and vascular disease, which has led to recent studies of endothelin antagonists in resistant hypertension. He clarified the pathophysiological role of angiotensin II and aldosterone on damage to blood vessels, elucidated the vasoprotective actions of peroxisome proliferator-activated receptors, and revealed the role of inflammation and T-regulatory lymphocytes in vascular remodeling in high blood pressure. His identification of the differential effects of anti-hypertensive drugs on vascular structure led to clinical trials that replicated those findings in humans. Dr. Schiffrin is currently exploring connections between the immune system and cardiovascular disease, and is considered a leading expert on innate immunity in the pathophysiology of hypertension.
“We often talk about the ‘Death Valley’ between the development of key biomedical concepts and their application in clinical research and ultimately clinical care,” wrote Ross Feldman, the Chair of Medicine at Memorial University. “Dr. Schiffrin’s work is important since it has survived that crossing.”
The Physician-in-Chief of the Sir Mortimer B. Davis-Jewish General Hospital and a Canada Research Chair in Hypertension and Vascular Research at the Lady Davis Institute of Medical Research, he is the author of more than 545 peer-reviewed publications and many book chapters, as well as the editor of four books on molecular and clinical aspects of vascular disease and hypertension. He was Associate Editor of Hypertension, a journal of the American Heart Association (AHA), and is now Editor-in-Chief of the American Journal of Hypertension. He is Immediate Past President of the International Society of Hypertension and is the President and Chair of the Board of Hypertension Canada.
Dr. Schiffrin received the Distinguished Service Award of the Canadian Hypertension Society, as well as the Irvine Page-Alva Bradley Lifetime Achievement Award and the Excellence Award for Research in Hypertension, both from of the High Blood Pressure Research Council of the American Heart Association. He was elected Fellow of the Royal Society of Canada in 2006, and was awarded the Order of Canada in 2010.
Connie Eaves, a Professor in the Department of Medical Genetics at UBC and a Distinguished Scientist at the BC Cancer Agency, has made seminal contributions to understanding the stem cells of normal blood, the mammary gland, leukemia and breast cancer. She developed the first methods for detecting and measuring blood and later mammary stem cells at the single-cell level both in vitro and in vivo and these remain the gold standard in these fields. Her group also established the diversity of these primitive cells and determined how they are regulated. These findings have contributed critical information about the conditions required to grow human blood stem cells in vitro, a process that could revolutionize the future of bone marrow transplantation and gene therapy.
An internationally recognized expert in chronic myeloid leukemia (CML), Dr. Eaves and her husband, Dr. Allen Eaves, discovered a large persisting population of normal blood stem cells in most patients with CML. These and their subsequent findings about stem cells present in CML patients transformed the way hematologists and oncologists began to think about this disease, spurring efforts to develop treatments that would selectively eliminate the leukemic cells without the need for a bone marrow transplant. This included their discovery of a predominant non-dividing subset of cancer stem cells in CML patients providing an explanation for the frequently short-lived responses obtained with many anti-cancer drugs historically selected simply because they kill dividing cells.
“When CML is eventually cured via powerful targeted agents acting together with some stem cell-reshuffling therapy, we will all owe Connie a huge debt for laying the foundation for this breakthrough,” wrote George Q. Daley, a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Director of the Stem Cell Translation Program at Boston Children’s Hospital and the Dana Farber Cancer Institute.
More recently, Dr. Eaves has been successful in developing experimental systems that generate malignant human cells from initially normal human blood and mammary cells. The goal is to use these defined systems to identify the first events in this process.
Dr. Eaves and her husband co-founded the Terry Fox Laboratory at the BC Cancer Agency in 1981, and she has served as its Deputy Director and Director, as well as Vice President, Research for the BCCA. She has also played senior leadership roles in many national and international research funding and policy groups, including the former National Cancer Institute of Canada, the Canadian Stem Cell Network and Genome Canada. She has published nearly 500 papers, many in leading journals and has received numerous awards, including the Henry Stratton Award from the American Society of Hematology, the Lifetime Achievement Award from Canadian Blood Services (shared with her husband), and the International Chronic Myeloid Leukemia Foundation Rowley Prize. But Dr. Eaves believes her greatest legacy will be the numerous outstanding graduate students and post-doctoral trainees she has mentored, many of whom have since become scientific leaders.