John Dick, PhD
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Dr. Dick's research aims to understand how stem cells can be manipulated. He is world-renowned for his development of an in vivo repopulation assay using the NOD/SCID mouse. Human stem cells are found in the bone marrow and are pluripotent: they give rise to all the cellular elements of the blood. Since there was no method to study the development of the human blood system until this model was developed, studies of the human hematopoietic system and diseases of the blood were limited. This model has transformed the study of both normal and leukemic human blood systems.
The assay involves reconstituting immune deficient SCID mice with either normal human bone marrow or cord blood, or with cells from patients with genetic deficiencies or leukemia. The immune deficient mouse cannot reject the human cells, and thus the human cells readily proliferate and differentiate, generating human hematopoietic cells of erythroid, lymphoid, and myeloid lineage in the mouse.
The mouse model was initially developed to understand and define both normal and leukemic stem cells. In acute myeloid leukemia, only leukemic stem cells can initiate the disease and there is little understanding of which normal cells become transformed in the initiation of leukemia. That is why it is important to characterize the developmental programs of both cell types. Without an understanding of how they are different, the mechanism by which the leukemic process alters the development of the normal blood system will never be understood. Effective anti-leukemia therapy must target the leukemic stem cell to completely eradicate the disease.
Using the mouse model, it is possible to identify and characterize the leukemic stem cell and determine where it comes from. Until now, this process has always been a mystery. With this model, we will now be able to see inside that black box, and gain a more complete understanding regarding how the molecular pathways differ in normal and leukemic blood systems. Then we will be able to devise therapies to disrupt the molecular process that leads to leukemia and hopefully prevent it from occurring.
Dan Dumont, PhD
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The focus of Dr. Dumont’s research is angiogenic and lymohangiogenic signaling. The receptor tyrosine kinase (RTK) family of cell surface proteins plays key roles in cell-cell communication in multi-cellular metazoan organisms. Genetic and biochemical studies on this large family of proteins have shown that different RTKs are responsible for transducing important developmental, proliferative, cell survival, and migratory signals from outside to inside the cell. The development and proper functioning of cell systems as diverse as the compound eye in the fly, the vulva in the nematode, and hematopoiesis and endothelial growth in the mouse all depend on intact signaling pathways that are controlled by RTK family members.
Dr. Dumont's lab is investigating the signal transduction pathways of different RTKs during vascular development in the mouse. Vascular endothelial cells constitute an unusually quiescent epithelial cell population. The turnover rate of both large and small vessel endothelium is very low. The mechanisms that underlie this growth control are not well understood, and the factors that initiate and control subsequent proliferation are unknown. It is clear, however, that vascular growth occurs under nonpathological conditions (e.g. wound healing, corpus luteum formation, and development) and that this growth is somehow terminated at the correct time. In contrast, uncontrolled vessel growth (including tumor vascularization, diabetic retinopathy, and arthritis) is associated with many different diseased states. The determinants, which control these processes, remain unknown however the study of peptide growth factors, their receptors, and their downstream substrates will provide both a biochemical and genetic entry point in to the elucidation of the underlying controls of these processes.
Dr. Dumont's group uses gene targeting in embryonic stem cells, transgenic mice and receptor biochemistry to attempt to address the importance of these different RTKs and their related signal transduction pathways during vascular growth in development and in disease.
Michael Fehlings, MD, PhD
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Dr. Fehlings received his MD in 1983 from the University of Toronto. Following a surgical internship at Queen’s University in 1983-84, Dr. Fehlings entered the University of Toronto Neurosurgical Training Program. During his residency, Dr. Fehlings worked on experimental spinal cord injury for his PhD studies, receiving his PhD in 1989 from the Institute of Medical Sciences. Dr. Fehlings became a Fellow of the Royal College of Physicians and Surgeons of Canada in 1990. In 1991, he undertook a post-doctoral research fellowship at NYU Medical Center, that was followed by a clinical spine fellowship at NYU. Dr. Fehlings joined the Neurosurgical Staff at the Toronto Western Hospital in 1992. He is currently Professor in the Department of Surgery, full member of the Institute of Medical Sciences School of Graduate Studies, Director of the Spinal Program at the Toronto Western Hospital, Director of the Neural and Sensory Sciences Program at the University Health Network and Krembil Chair in Neural Repair and Regeneration. His main clinical interests are in spinal neurosurgery, and his research focus is in molecular mechanisms underlying spinal cord injury.
Dr. Fehlings’ primary research interest is neurotrauma, including traumatic brain and spinal cord injury (SCI). The research has focused on an examination of the cellular and molecular mechanisms underlying the pathophysiology of SCI. The lab has clarified the cellular and molecular mechanisms underlying posttraumatic white matter degeneration after SCI. Persistence of as few as 10% of axons, particularly in non-pyramidal tracts is associated with substantial recovery of hindlimb function. Accordingly, strategies, which are able to restore or protect a small number of axons in the spinal cord, can be associated with functionally significant neurological recovery. Using novel in vitro and in vivo models of SCI, the lab has demonstrated molecular and functional roles of ion channels (Na + , K + , Ca 2+ ), ionotropic and metabotropic glutamate receptors, and calcium activated proteases, including calpain on posttraumatic axonal degeneration. This work has provided a number of important potential therapeutic targets to direct efforts at minimizing neurological disability after neurotrauma including brain and spinal cord injury.
Current studies in SCI are focused on examining mechanisms underlying glial and neuronal apoptosis, the role of K + channels in axonal dysfunction, and excitotoxic-mediated white matter degeneration. The role of AMPA/Kainate and metabotropic glutamatergic cell death after neurotrauma is being examined by combining molecular approaches (knockout mice and antisense gene deletion) , cellular electrophysiology (whole cell and single channel patch clamp; sucrose gap axonal recording), and examination of changes in protein and gene expression (Western blotting; confocal immunofluorescence; RNase protection; in situ hybridization) in tissue slice, cell culture and in vivo.
Mansoor Husain, MD
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Dr. Husain holds a Bachelor of Medical Science with Distinction (1984) and received the Gold Medal in Medicine with Distinction from the University of Alberta (1986). After a rotating internship (1986-87) and residencies in Internal Medicine (1987-91) and Cardiology (1991-3) at the University of Toronto, Dr. Husain undertook postdoctoral studies in the Department of Biology at the Massachusetts Institute of Technology (1993-7). Dr. Husain returned to the University of Toronto in 1997, where he is now Associate Professor in the Departments of Medicine, Physiology, and Laboratory Medicine & Pathobiology (2004).
Dr. Husain held a Clinician-Scientist Award from the Canadian Institutes of Health Research (CIHR), and now holds a Career Investigator Award of the Heart & Stroke Foundation of Ontario (HSFO). Dr Husain is a Scientist at the Toronto General Hospital Research Institute and Director of the Transgenic Animal Core for a CIHR Program Project Grant in Heart Failure Research.
Dr. Husain's basic research is on the molecular mechanisms underlying hypertension, atherosclerosis, and heart failure. His laboratory has developed unique mouse models of these human cardiovascular diseases, and employs conditional and tissue-specific gene regulation to understand the pathophysiology of particular molecular pathways. Dr. Husain's long-standing efforts aimed at understanding the phenotypic modulation of the vascular smooth muscle cell (VSMC) have an entered a new phase, in which studies of stem cells and in vitro models of VSMC differentiation are employed.
Dr. Husain's work has been funded by the CIHR, HSFO, Canada Foundation for Innovation, Ontario Research & Development Challenge Fund, and a Premier’s Research Excellence Award.
Clinically, Dr. Husain is Associate Director of the Cardiac Intensive Care Unit at the Toronto General Hospital and an attending physician in the Nuclear Cardiology Laboratories of the University Health Network.
Norman Iscove, MD, PhD
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The production of blood cells and lymphocytes is maintained throughout life by multipotential hematopoietic stem cells in the bone marrow. When stem cells enter active growth, they generate two kinds of progeny: some are pre-programmed to differentiate, while others, generated in a process known as self-renewal, remain as stem cells. This guarantees the persistence of stem cells and the permanence of blood cell formation. Competition between self-renewal and differentiation of stem cells is a feature common to the maintenance not only of most normal tissues but also of most cancers. Dr. Iscove’s lab is concerned with the genes and mechanisms that specify self-renewal and differentiation in normal and leukemic hematopoietic stem cells.
Dr. Iscove’s lab is interested in identifying known and novel genes that are specifically induced or downregulated in stem cells or subsequent early steps of differentiation. For these studies, there is a need to sample transcripts specifically from the various kinds of hematopoietic precursor cells. The lab has made advances in three areas of such stage-specific transcripts at our disposal. The lab has developed technology for amplifying all transcripts present in a single sampled cell while preserving relative abundance relationships. By exploiting the similarity of differentiation potential of sibling cells within nascent clones, the lab has built an extensive archive of amplified cDNA samples representative of key stages in hematopoietic precursor development. Finally, the lab has been able to purify the most primitive stem cells to near homogeneity, achieving in vivo reconstitution from each single cell injected in to suitable murine hosts.
Michael Kutryk, MD, PhD
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Dr. Kutryk received his PhD and MD from the Faculty of Medicine at the University of Manitoba in 1990. He completed Specialty Certification in Internal Medicine at McGill University at the Royal Victoria Hospital. He then undertook Subspecialty Training in Cardiology at McGill followed by a 4-year post-doctoral research training program in Interventional Cardiology at the Erasmus University and University Hospital Rotterdam - Dijkzigt. Dr. Kutryk is currently a cardiologist and clinician scientist at St. Michael’s Hospital and an Assistant Professor at the University of Toronto.
Dr. Kutryk’s main research interest is biologically-coated stents/EPCs. Dr. Kutryk’s research examines how the introduction of a coated stent could eliminate scarring and reduce blockages, as well as a synthetic graft that could be used to repair the endothelial layer of the blood vessel. The use of synthetic material for coronary bypass procedures could potentially avoid utilizing the patient’s blood vessels from the leg or arteries from the chest wall. Dr. Kutryk also continues his work with Dr. Duncan Stewart in angiogenesis, a procedure that stimulates the growth of new blood vessels in the heart.
Freda Miller, PhD
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Dr. Miller obtained her PhD in Medical Sciences from the University of Calgary in 1984 and completed her postdoctoral research at the Scripps Research Foundation. Dr. Miller is a cell and molecular neurobiologist at the Hospital for Sick Children Research Institute, a Professor at the University of Toronto, the Canada Research Chair in Developmental Neurobiology, and a Fellow of the Royal Society of Canada. Dr. Miller has authored more than 100 scientific papers, reviews, and book chapters, and has 13 patents (issued and pending). Dr. Miller is best known for her studies of neural stem cells and of neuronal growth, survival, and apoptosis. Major findings from her lab have provided evidence that mammalian skin contains a multipotent stem cell that can be isolated and purified (Nature Cell Biology 3, 778-784, 2001; Nature Cell Biology 6, 1082-1093, 2004), that the p75 neurotrophin receptor is apoptotic in neurons (Journal of Cell Biology 140, 911-923, 1998), and that the p53 family plays a key role in regulating the life and death of mammalian neurons (Science 289, 304-306, 2000; Neuron 48, 743-756, 2005). In addition, Dr. Miller is a founder of Aegera Therapeutics Inc., a Canadian biotech company.
Cindi Morshead, PhD
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Dr. Morshead received her PhD at the University of Toronto in the Department of Anatomy and Cell Biology. She teaches Neuroanatomy in the MScPT Program in Rehabilitation Sciences, as well as contributes to the Neuroanatomy course of the Brain and Behaviour block of first year medicine. She is a member of the Stem Cell Network and Toronto Stem Cell Group
Dr. Morshead’s academic interests include the study of neural stem cells in the adult mammalian central nervous system.Her research is focused on the fundamental characterization of neural stem cells and their potential role in neural regeneration in the adult brain. She is currently using in vivo transplantation and injury models in addition to in vitro models to manipulate neural stem cells and examine their lineage commitment. Some of the in vitro models involve live cell imaging to visualize and follow individual stem cells and their progeny in controlled microenvironments. In addition, the lab is interested in the use of biomaterials in combination with neural stem cells towards the ultimate goal of enhancing the regenerative capacity of the nervous system.
Andras Nagy, PhD
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Dr. Nagy is a Senior Investigator of Development and Fetal Health and Professor, Department of Medical Genetics and Microbiology, University of Toronto. In 1974 Dr. Nagy completed his B.A. (M.A.) in Mathematics and in 1979 completed his Ph.D. in Genetics, both at Lorand Eötvös University Budapest. Dr. Nagy currently holds the Canadian Institute of Health Records Senior Scientist Award (2002-2007). In partnership with Bristol-Myers Squibb he also was awarded the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Scientist award 1996-2001.
The Nagy laboratory is interested in using mouse genetics to study mammalian development and to apply this knowledge to human disease. Dr. Nagy is also developing new, powerful tools for genetic approaches and phenotype analysis for these ongoing studies. Another main activity of the Nagy lab is connected to mammalian genomic imprinting.
Janet Rossant, PhD
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Dr. Rossant trained at the University of Cambridge and Oxford University. She was an Associate Professor of Biological Sciences at Brock University until 1985. She became an Associate Professor of Medical Genetics at the University of Toronto and joined the Samuel Lunenfeld Research Institute in September of that same year. Dr. Rossant is currently Chief of Research at the Hospital for Sick Children and University Professor at U of Toronto. She is a Distinguished Scientist of the Medical Research Council of Canada. Dr. Rossant was awarded the 2000 NCIC/Eli Lilly Robert L. Noble Prize for excellence in cancer research, the 2004 Killam Prize for Health Research, and the CIHR Michael Smith Prize in 2005.
Dr. Rossant's research interests centre on understanding the genetic control of normal and abnormal development in the early mouse embryo. She uses exciting new technologies to genetically manipulate the mouse genome to address problems that may arise in development. Since these mouse cells represent the early cells that form the placenta in humans, insight in to developmental abnormalities in early pregnancy is possible.
Molly Shoichet, PhD
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Dr. Shoichet received her S.B. in Chemistry from MIT (1987) and her PhD in Polymer Science and Engineering from the University of Massachusetts, Amherst (1992). She worked at CytoTherapeutics Inc., on encapsulated cell therapy before being recruited to the University of Toronto in 1995. Dr. Shoichet holds the Canada Research Chair in Tissue Engineering and is a Professor of Chemical Engineering & Applied Chemistry, Chemistry and Biomaterials & Biomedical Engineering at the University of Toronto. A recipient of prestigious distinctions such as NSERC’s Steacie Fellowship, CIAR’s Young Explorer’s Award, CSChE’s Syncrude Innovation Award, and Canada’s Top 40 under 40™. Dr. Shoichet has published over 220 papers, patents and abstracts, and has been invited to speak at over 120 institutions worldwide.
Dr. Shoichet is an expert in the study of polymers for regeneration- materials that promote healing in the body. Dr. Shoichet’s studies are focused on promoting nerve regeneration after spinal cord injury, for which there presently is no cure. While researchers gain a better understanding of the central nervous system, Dr. Shoichet is leading an effort to find ways to overcome injury through novel regeneration and drug delivery strategies. Dr. Shoichet is leading a collaborative project on targeted delivery strategies in cancer, building on the fundamental polymer and drug delivery strategies invented in her research group. Dr. Shoichet is the Scientific Founder of two companies that were formed based on technology invented in her laboratory and is actively involved in Matregen Corp., a drug delivery company.
Bill Stanford, PhD
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Dr. William Stanford is an Assistant Professor at the Institute of Biomaterials & Biomedical Engineering and the Institute of Medical Science at the University of Toronto. He is also an Associate Scientist at the Samuel Lunenfeld Research Institute and Director of the Gene Trap Project at the Centre for Modeling Human Disease. Dr. Stanford received his PhD in 1994 from the University of North Carolina, Chapel Hill, where he also undertook post-doctoral studies, and then also did some post-doctoral work at the Samuel Lunenfeld Research Institute.
The Stanford lab is focused on developing and applying genetic tools to analyze the molecular mechanisms that control stem cell function and application of these insights to tissue engineering and regenerative medicine. The research projects are organized in three inter-related topics: adult stem cell biology, tissue engineering using embryonic stem (ES) cells, and the development and analysis of mouse models of human disease.
The synthesis of these research areas is illustrated by a project which utilized mutagenesis of mouse ES cells to develop a mouse model of type II (or age related) osteoporosis, which results in a defect in the self-renewal capacity of mesenchymal stem cells, whose derivatives generate new bone mass throughout our lives.
Duncan Stewart, MD
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Dr. Stewart received an MD from McGill University in 1977, where he also performed residency training in Internal Medicine and Cardiology. He completed research fellowship training in Physiology and Pharmacology in Freiburg, Germany. In 1987, he returned to Canada to become an Assistant Professor of Medicine at McGill and staff cardiologist at the Royal Victoria Hospital, and established a Vascular Biology Laboratory with a major interest in endothelial factors. In 1994, he assumed the position of Head of Cardiology at St. Michael's Hospital, in 1997, became the Director of Cardiology of the University of Toronto, and was awarded the Dexter Man Chair of Cardiology. He was promoted to Full Professor of Medicine in 1999.
Dr. Stewart's research interests focus on the endothelium in health and disease, and in particular in translational research. His research seeks to use molecular approaches in the prevention and treatment of vascular diseases. He has developed several novel gene-based approaches to the therapy of cardiovascular diseases, specifically, a new cell-based gene transfer technology for the treatment of pulmonary hypertension which is in the late phases of preclinical development. His group has initiated Canada's first clinical trials in gene therapy for cardiovascular disease, in therapeutic angiogenesis for end-stage coronary artery disease.
Dr. Stewart is past Chair of the MRC Cardiovascular "A" Review Committee and belongs to numerous national and international research organizations. He has published over117 peer-reviewed manuscripts and is on the Editorial Board of scientific journals such as Circulation Research. He has been intimately involved in the organization of international meetings and is past Chair of the Scientific Program Committee for the Canadian Cardiology Congress and the Research Policy Committee for the Heart & Stroke Foundation of Ontario.
Charles Tator, CM, MD, MA, PhD, FRCSC, FACS
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Dr. Tator is the Robert Campeau Family Foundation Chair in Brain and Spinal Cord Injury Research at the University of Toronto and the Toronto Western Hospital, and he is currently President of ThinkFirst Canada Penser d’Abord, an injury prevention Foundation dedicated to the prevention of brain and spinal cord injuries, especially among children and youth.
In l997, Dr. Tator received the Lifetime Achievement Award of the Canadian Brain Injury Coalition in recognition of his work in the field of Neurotrauma. In 2000, he was appointed a Member of the Order of Canada. In 2001, he was awarded the Dr. Jonas Salk Award of the Ontario March of Dimes in recognition of achievement as a leader in the prevention, research, and treatment of spinal cord injury in Canada. In 2002, The Department of Surgery of the University of Toronto established the Charles Tator Surgical Resident Mentoring Prize to recognize his contribution to the training of residents in research. In the same year, Dr. Tator received the Grass Prize for research from the Society of Neurological Surgeons. In 2003, he was inducted into the Terry Fox Hall of Fame. He has been an editorial board member of several journals, and is currently a Section Editor for the Journal of Neurotrauma.
Dr. Tator has current operating grants from the Canadian Institutes for Health Research, The Natural Sciences and Engineering Research Council, the Canadian Paraplegic Association, the Christopher Reeve Foundation and the Ontario Neurotrauma Foundation. His current research is focused on axonal regeneration in the injured spinal cord, principally with stem cell strategies and bioabsorbable synthetic guidance channels. He is exploring the use of endogenous stem /progenitor cells to enhance axonal regeneration in the injured adult rat spinal cord, and is also transplanting brain and spinal cord derived neurospheres into the injured adult spinal cord. He has supervised more than 50 graduate students and postgraduate fellows, and has authored 275 peer reviewed publications.
Graham Wright, PhD
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Dr. Wright is Scientist at the Sunnybrook and Women's Research Institute, Research Director, Heart & Circulation Program at Sunnybrook and Women's College Health Science Centre, and Professor, Medical Biophysics at the University of Toronto. He received a PhD Electrical Engineering, Stanford University. His research is focused on cardiovascular imaging, particularly MRI, for disease assessment/intervention guidance.
Research efforts include basic biophysics to characterize the relationship between MR signals and underlying physiology in blood and tissue, engineering to develop more effective methods to acquire, analyze, and visualize medical images, application of these tools to assessment, treatment planning, and therapy guidance in ischemic and congenital heart diseases and neurovascular and peripheral vascular diseases.
Peter Zandstra, PhD
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Dr. Zandstra is the I’Anson Associate Professor of Tissue Engineering and the Canada Research Chair in Stem Cell Bioengineering at the Institute of Biomaterials and Biomedical Engineering at the University of Toronto. Dr. Zandstra’s work integrates engineering, mathematical, and biological approaches and has contributed to the development of clinically and industrially relevant and academically recognized technologies based on the design of bioprocesses for the growth and differentiation of adult and embryonic stem cells. Direct applications of this work include tissue and cellular engineering and gene therapy.
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