The overall goal of our research program is to develop strategies that exploit the ability of our innate defense to fight viral infections and cancers. Over the last 10 years our laboratory has focused on 2 central research questions: 1) How do type I IFNs and NK cells provide early innate protection against viral infections while controlling the immune cells to avoid overactivation and immunopathology, and 2) Why are human NK cells dysregulated in the tumor microenvironment (TME). and how can we overcome this to harness the anti-tumor potential of human NK cell.

• Innate antiviral immunity

Successful host defense requires tight control of inflammation to mount an effective immune response while limiting damage to the host. Loss of such inflammatory control can result in a pathological dysregulated immune response characterized by immune cell hyperactivity and mass production of inflammatory cytokines (cytokine storm) that causes tissue damage. In fact, mortality from most acute infections, including bacterialsepsis, hemorrhagic fevers, seasonal influenza, and more recently SARS-CoV-2, is rarely due to the pathogen itself, but rather to such hyperinflammation by the host’s immune system, causing organ damage and subsequent failure. There is a critical need to develop therapies that effectively target hyperinflammation without compromising host resistance. However, a major limitation to this end is that the cellular mechanisms that initiate and propagate the cytokine storm remain poorly understood. Our research aims are to elucidate the mechanism(s) and pathways by which our innate immune system, particularly IFNs and NK cells, excerpts their immunoregulatory functions.

• NK cell-based cancer immunotherapy

A major goal of our research is developing efficacious and safer treatments for hard-to-treat solid tumors. To do this, we are harnessing the tumor killing ability of Natural Killer (NK) immune cells, which have an intrinsic ability to distinguish between healthy and malignant cells. Advances in the ex vivo expansion of human NK cells has enabled the adoptive transfer of NK cells to treat patients, showing clinical success against hematologic malignancies. However, there are still two major limitations to overcome in order to successfully combat solid tumors: 1) efficient homing of the adoptively transferred immune cells to the solid tumor microenvironment (TME), and 2) the hostile and immunosuppressive TME. Our lab aims to overcome these two limitations to enhance NK cell-based cancer immunotherapy for solid tumors.

Please visit: ashkarlab.com

My lab is interested in learning more about how protein homeostasis (also known as proteostasis) contributes to inflammatory and fibrotic lung disease. We believe that endoplasmic reticulum stress and the unfolded protein response contribute to the progression of these pathologies and that we will be able to slow down disease progression by modulating this fundamental and important stress response.

The major focus of my research is on various aspects of the molecular biology of vascular disease and thrombosis. Other interests include the role of endoplasmic reticulum stress in human disease.

A wide range of molecular biological techniques are used including, RNA and DNA isolation and purification, agarose and polyacrylamide gel electrophoresis, Northern and Western blotting, polymerase chain reaction, eukaryotic and prokaryotic protein expression systems, mRNA differential display, and screening of cDNA microarrays.

Research Areas:

• Cancer diagnosis (RA)
• Cancer molecular targets (RA)
• Cancer progression and metastasis (RA)
• Haematological tumours (RA)

We are exposed to potentially dangerous microorganisms every moment of every day. Potential pathogens are in the air we breathe, the things we touch, and the food we eat. Even our microbiota harbours potential pathogens, yet we are healthy most of the time. Specialized white blood cells called macrophages are sentinel cells that help maintain the relationship with our microbiota while protecting us from invading pathogens. Macrophages, and their precursors, monocytes, are attuned to their microenvironment. They continually sense signals from the tissues around them and adjust their behaviour. As we age, levels of inflammatory cytokines, reactive oxygen species, damaged proteins, and bacterial products increase, and these external signals alter monocyte and macrophage development and function in ways that increase the risk of infection.

As we age, our adaptive immune system is also continuously remodelled by extrinsic factors such as previous exposures to pathogens, medications, and environmental exposures, and intrinsic factors such as biologic sex, and chronic health conditions. Age-related changes in the adaptive immune response alter responses to vaccination.

Collectively, age-associated inflammation and immune remodelling increase the risk of respiratory infections, decrease vaccine efficacy, and contribute to the long-term health issues that occur after infection. The vision of the Bowdish lab is to provide older adults with more years of healthy, independent living by preventing serious respiratory infections.  To do this we aim to understand why and how the aging immune system changes, uncover why older adults are more susceptible to respiratory infections, and find novel treatments to prevent both infection and the long-term health issues that can occur after serious infections (See www.bowdish.ca for details).

Our group is studying the mechanisms by which the adaptive immune system recognizes and responds to tumors. Our specific interest is the development of immunological strategies to fight cancer.

Cancer immunotherapy aims to augment the ability of the immune system to recognize and destroy tumors. Such an approach should provide the ideal adjuvant to current therapies since immune cells have the unique capacity to circulate and “seek out” malignant cells within the body, thereby clearing deposits of micro-metastases. Furthermore, since immune cells can eradicate quiescent cancer stem cells that are typically resistant to chemotherapy, immunotherapy offers the potential for a life-long cure. Indeed, recent clinical trials have provided unequivocal evidence that the immune system can be harnessed to mediate tumor regression in humans. However, successful implementation of immunotherapy has been restricted to a specific set of cases and further work is required to develop this as a routine and practical method of treatment.

My lab has taken a multi-modal approach to treating cancer by employing a combination of cancer vaccines, adoptive T cell therapies and oncolytic viruses. We believe that such multi-pronged strategies are the best way to attack the tumor. Our research is supported through research grants from the Terry Fox Foundation and the Canadian Institutes for Health Research.

In murine models, we have observed that recombinant vaccines were highly efficient agents for evoking immunity against cancer antigens. However, despite the robust immune response produced by these vectors, they are typically ineffective against established tumors. We have recently discovered that tumors adapt rapidly to immune attack and create an localized immune suppressive environment that shuts down the ability of T cell to elaborate their effector functions. This rapid adaptation is induced by cytokines, such as IFN-gamma, which are key effector molecules produced by T cells to suppress tumor growth. Thus, the effector molecules produced by tumor-specific T cells can be considered double-edged swords that act to both suppress tumor growth and to activate immune suppressive pathways. Further investigation revealed that the tumor adaptation can be overcome by enhancing the rate at which immune cells attack the tumor; this can be achieved by infusing the host with tumor-specific T cells prior to vaccination. We have employed transciptional analysis to investigate the microenvironment of the tumors following effective treatments (i.e. tumors regressed) and ineffective treatments (i.e. tumors did not regress). Strikingly, we found an 85-gene signature in our murine studies that was predictive of outcome in humans indicating that global changes we observe in mouse models are relevant to human disease. We are currently working to refine our signature to determine whether it can be used as a predictor of outcome following immune intervention in humans.

As stated in the previous paragraph, our studies have revealed that immune attack on tumors must be fast and furious to overcome tumor adaptation. One way to achieve a swift and overwhelming immune attack is to culture tumor specific T cells ex vivo and infuse a massive bolus injection of T cells (a process termed adoptive T cell therapy or ACT). Although naturally-occuring tumor-specific T cells are rare, clinical application of ACT can be enabled by engineering naïve T cells to express tumor-specific chimeric antigen receptors (CARs), bypassing the need to select rare tumor-specific T cells. We are currently investigating the parameters that influence optimal ACT using CAR-engineered T cells. In particular, we are examining the local effects of these T cells within the tumors to understand the reaction of the tumor to this form of treatment. We have also developed a novel tool for directing T cells to attack tumors known as a tri-functional T cell-antigen coupler (Tri-TAC), which operates through a mechanism distinct from a CAR. Our efforts are currently directed at optimizing Tri-TAC function and the development of novel costimulatory proteins that are triggereed by targets on the tumor. To enhance the activity of our ACT strategies, we are also working with oncolytic vaccines which are engineered viruses which serve the dual purpose of oncolytic agents that effectuate direct tumor killing and vaccination agents which enhance T cell function. The data generated by our research reflects a composite of multiple interacting pathways that are engaged simultaneously.

We have been working with our colleagues at the Juravinski Hospital (Ronan Foley, Mark Levine, Ros Juergens) to evaluate cancer vaccines in early phase human trials. We are very excited to be a part of the Ontario Regional Biotherapeutics Program (ORBiT) that is sponsored by the Ontario Institute for Cancer Research. The ORBiT program, directed by John Bell, is focused on early phase clinical trials where cancer vaccines will be combined with oncolytic viruses and adoptive T cell transfer. This program provides a clear path for rapid translation of promising immunotherapies developed through our preclinical program.

Abnormal kidney development is a major cause of childhood renal failure. It arises from a failure in the fundamental processes that guide kidney development. Despite the importance of normal kidney development to human health the underlying molecular mechanisms remain poorly understood. My lab is interested in identifying the mechanisms that control kidney development. Having a better understanding of these processes will allow us to make informed hypotheses into the mechanisms that lead to disease.

Giada De Palma is an Assistant Professor and research associate with Dr. Premysl Bercik and Stephen M. Collins at the Farncombe Family Digestive Health Research Institute, at McMaster University. The focus of her research is on the interaction between microbiome, diet, gut physiology, and behavior in disorders of gut-brain axis interaction.

Dr. Judah Denburg’s main research thrust has been to investigate the mechanisms of allergic inflammation, with particular emphasis on hemopoietic cytokines and their role in activating the differentiation and recruitment of inflammatory cells such as eosinophils, basophils and mast cells. In addition, hemopoietic progenitor phenotyping has been utilized to discover new biomarkers to predict the development of allergic disease and asthma, in several national projects undertaken by the Allergy, Genes & Environment (AllerGen) Network of Centres of Excellence, which is under Dr. Denburg’s leadership.

Dr. Jeffrey Dickhout conducts research in the department of medicine, division of nephrology with laboratories located at St. Joseph’s HealthCare Hamilton in the Hamilton Centre for Kidney Research. His research area of interest is to better understand the mechanics involved in renal dysfunction including its connection to endoplasmic reticulum (ER) stress as well as the effects of diet and cardiovascular disease.

Specifically, he is interested in the effects of protein biosynthesis under pathophysiological stress conditions (i.e. ER stress) in chronic kidney disease and its effects on blood vessel structure and function (e.g. myogenic response). Further, the role of inflammation has also been implicated in kidney disease and is being investigated by the Dickhout Lab.

Dr. Dickhout’s research program is currently supported by CIHR were he holds funds as Principal Investigator into the role of endoplasmic reticulum (ER) stress in the development of kidney disease and the role of the unfolded protein response (UPR) in hypertension induced end organ damage.

Neurotrophic factors are proteins essential for nervous system development and function. The biosynthesis and regulation of neurotrophins such as NGF and BDNF are disrupted in many neurodegenerative and psychiatric diseases. My laboratory studies neurotrophin gene expression, regulation, signaling and trafficking and their role in Alzheimer’s disease and autism. By studying dysregulation of NGF and BDNF in these disorders, we have come to understand how the proper amount of neurotrophin reaches the proper cells at the right time, and the consequences if it doesn’t. We use human post mortem brain tissue, animal models and cell culture to study transcriptional, translational and post-translational regulation, signaling and transport of neurotrophins and their receptors in health and disease. Understanding how neurotrophins are dysregulated in Alzheimer’s disease and autism is crucial to identifying new therapeutic approaches and targets for these devastating disorders.

Molecular biology, biochemistry, cell culture, real-time qRT-PCR, Western blotting, ELISA, neurite outgrowth assays, animal models, behavioural assays.

Leukocyte recruitment is a specific cascade of molecules and events designed to bring the inflammatory cells to the site of infection or injury. My research examines the role of adhesion molecules, pro-inflammatory mediators and endogenous anti-inflammatory molecules in systemic inflammation. I am specifically interested in the factors that control leukocyte recruitment and clinical therapies, such as intravenous fluid or catheter materials.

I study the in vivo responses associated with septic shock, severe infection and gastrointestinal inflammation.

I use inflammatory models such as cecal ligation and perforation and local inflammatory mediators. We currently examine the liver microcirculation, the peritoneal surface and the bladder.

My research investigates the mechanisms of allergic inflammation in human models of allergic asthma. Ongoing clinical studies examine the effects of experimental therapies on allergen-induced changes in airway physiology and inflammation, with emphasis on the activation of leukocytes known to participate in the allergic response.

More specifically, research conducted in my laboratory examines the activation of eosinophils, basophils, and their progenitors in samples from airways, blood and bone marrow. We have shown that airway epithelial cell-derived products such as TSLP are important inducers of airway inflammation, in part through the activation of basophils.

My lab is developing models to study the pathology/immunology of human disease. My primary research focus is on Immunology, Mucosal Immunology, Infectious Disease and Virology. In particular, we are utilizing humanized mouse models to enable the comprehensive examination of viruses with human tropism such as Human Immunodeficiency Virus (HIV). With this model, we will perform studies examining Pre-exposure prophylaxis (PrEP), test vaccines and examine immune responses.
40% of deaths in people with HIV are from co-infections with tuberculosis (TB)(WHO-2016). The lack of HIV/TB co-infection models has been widely acknowledged in the field and experts have denoted this as an unmet scientific need. Thus, we are establishing a novel model of HIV/TB co-infection. This model is necessary because treatment, prophylaxis and disease outcome is different in individuals singly infected with HIV or TB or those co-infected with both. In general HIV/TB co-infections can be lethal because each tends to speed the progression of the other. HIV/TB co-infection is a global issue that requires further research and establishing this model to closely examine the phenomenon will be an important step towards managing and/or preventing this disease. We will ultimately use the HIV/TB co-infection model to understand immune responses in co-infected individuals and to develop vaccines and therapies that can decrease the mortality rates and health burden of this co-infection. We also use in vitro methods to investigate these areas.

Teaching Focus

Dr. Gillgrass is involved with the Faculty of Health Sciences teaching the following courses:

• HTH SCI 1J03- Life Sciences for Clinical Practice
• HTH SCI 3E03- Inquiry: Cancer Immunotherapy

In vivo models of thrombosis and coagulation

My research is focused on using in vivo models to study the pathobiology of thrombotic, hemorrhagic and vascular diseases. We also develop and evaluate novel point-of-care assays to inform the management of these diseases.

Dr. Thomas Hawke’s research focus is on the role and regulation of muscle satellite cells, the stem cell population of skeletal muscle, in health and disease states such as diabetes mellitus and limb girdle muscular dystrophy.

Skeletal muscle has an amazing capacity to regenerate following injury. The injury may be induced by a number of factors including heavy exercise, trauma or disease. The regenerative capacity of skeletal muscle is due primarily to a rare population of progenitor cells called muscle satellite cells. These cells have many characteristics of stem cells, including the capacity divide numerous times, self-renew their population and enter a state of quiescence when they are not needed.

The potential of this cell population is tremendous, however, the use of these cells for cell transplantation into patients with myopathies has yielded disappointing results. This is mostly due to a lack of knowledge regarding the regulatory mechanisms controlling these cells. It is only through a more thorough understanding of this cell population that their therapeutic potential be realized.

Using molecular, cellular and physiological techniques, we are attempting to define the regulation of this cell population in health and disease. Techniques used in the lab include: histology, immunohistochemistry, protein and RNA expression assays, isolated single fibre and primary myoblast cultures, in situ muscle stimulation to assess contractile function, adenoviral mediated overexpression and/or silencing and metabolic enzyme assays.

Dr. Hayward’s research focus is on the molecular aspects of hemostasis and platelet function.

Platelets have a central role in preventing excess bleeding and initiating events at sites of vessel injury. Basic and clinical research on platelet function has led to major insights into how bleeding and thrombosis are controlled in health and disease.

The central theme of our research is to study stored proteins in platelets, to determine their roles in controlling bleeding and thrombosis in health and disease. We are studying the functions of a novel, massive, polymeric protein called multimerin 1 that promotes platelet adhesion and is involved in forming platelet-rich thrombi at sites of vessel injury. Multimerin 1 is also the major platelet binding protein for a key accelerator of blood clotting called factor V.

My research group has characterized unique changes to the balance between blood coagulation and platelet function and clot dissolving pathways in a unique Canadian bleeding disorder called Quebec Platelet Disorder. This is a severe bleeding disorder associated with delayed bleeding and the generation of profibrinolytic platelets that contain increased urokinase plasminogen activator (an important activator of the clot dissolving pathway). This disease has provided an important example of how basic and clinical research can provide new insights into the regulation of blood coagulation.

Dr. Holloway’s research is focused on examining the mechanisms by which chemical insults in fetal or adult life can cause metabolic and reproductive endocrine disruption in animal and human populations. Of particular interest are chemicals we may intentionally expose ourselves to through lifestyle choices (e.g., smoking or vaping, cannabis use), psychiatric medications, and chemicals present in the environment related to resource extraction (i.e., coal mining, oil and gas extraction and logging). Dr. Holloway’s lab also uses samples collected as part of biomonitoring studies to assess impacts of resource extraction on the health of traditional foods. Using cellular and molecular techniques, the Holloway Lab aims to discover the impact of these chemicals on metabolic and reproductive systems and uses interactive methods to translate key findings to stakeholders. 

Molecular immunology of allergen-induced airways inflammation and remodeling in, primarily, murine model

Our goals are to dissect fundamental aspects of the pathogenesis of this process with a view to identify/develop novel therapeutic targets/strategies. Specific projects investigate the role of certain cytokines, chemokines and co-stimulatory molecules; others include an investigation of dendritic cells, the development of genetic-based immunotherapy strategies and the interactions between viruses and allergens.

A considerable part of our research is now carried out in experimental models in vivo using ragweed and house dust mite. In addition, we have established a model of peanut-induced anaphylaxis and have developed a new research direction. As tools, we used gene transfer strategies, flow cytometry analysis, standard immunological methods, airways physiology, TaqMan TM, and gene-gun technology.

Elucidate mechanisms by which hormones regulate infectivity and immune responses to sexually transmitted diseases such as Chlamydia, Herpes Simples Virus-2 and HIV-1. Understanding these mechanisms will be critical in developing successful vaccine strategies to STDs. We have previously shown that sex hormones play a critical role in regulating immune system in the female genital tract.

Role of factors such as cytokines and chemokines that initiate and regulate immune responses in female genital tract and their interaction with sex hormones; Expression of receptors and co-receptors to herpes and HIV and their regulation by sex hormones; Studies on infectivity of human and mouse epithelial cells by HSV-2 and HIV and changes in infectivity and immune responses under different hormonal conditions; in vivo regulation of mucosal immune responses in the genital tract to viral and bacterial STDs by sex hormones.

In vitro cell cultures of primary genital tract cells and cell lines to examine infectivity and cellular responses; in vivo infection of ovariectomized mice followed by hormone replacement to examine immune responses in intact animals; cellular and molecular assays to examine differential cytokine and chemokine expressions such as RNase protection assays and gene array analysis; antigen specific T and B cell immune responses; confocal microscopy; flow cytometry.

Research interests include clinical application of new diagnostic tests with particular interest in cardiac and cancer biomarkers. This research falls within the area of Clinical Chemistry, sometimes called Clinical Biochemistry, which uses analytical techniques to evaluate an individual’s health. Substances within the human body are measured from body fluids, such as blood, to obtain information on the individual’s clinical status. This information may help physicians identify disease (i.e., aid in the diagnosis), assess prognosis (i.e., risk stratification) and monitor or modify the therapy being administered. Specific analytical techniques employed in the research laboratory include automated immunoassays and multiplex protein platforms.

Major research interests include immunology, gastrointestinal (GI) inflammation, interplay among immune, microbial and endocrine systems in GI tract and host defence mechanism in GI infection.

The methodologies used in the laboratory include cell culture, immunohistochemistry, immuno-fluorescence, lymphocyte proliferation study, ELISA, multiplex immunoassay system, western blotting, flow-cytometry, laser capture micro-dissection, denaturing gradient gel electrophoresis and RT-PCR

Our research focuses mainly in the biochemistry of blood coagulation and fibrinolysis, identifying and characterizing various molecular mechanisms of hemostasis. Current proteins of interest include, but not limited to plasminogen, fibrinogen, thrombin-activatable fibrinolysis inhibitor (TAFI), and coagulation factor V(a).

Our research focuses on these key areas:

• Mechanisms of fibrinolysis regulation
• Role of TAFI in modulating fibrinolysis
• Role of platelets in blood coagulation and fibrinolysis

The type of bench work that is carried out at our laboratory includes protein-protein interaction, enzymology, protein chemistry, recombinant protein expression, protein purification/isolation, and protein analysis.

To investigate the mechanism of impaired wound healing after acute or chronic lung injury, which leads to progressive fibrogenesis in the lung parenchyma and airways and can result in respiratory failure.

The growth factors produced in the lung that trigger progressive fibrogenesis. The differentiation of local fibroblasts into myofibroblasts. The recruitment of circulating mesenchymal progenitor cells to the site of tissue injury. Epithelial mesenchymal transition in the lungs. Drug effects on the lung fibrogenesis, use of molecular therapies.

Animal models of lung fibrosis. Adenoviral gene transfer. Analysis of gene expression and signaling cascades. Progenitor cell biology. Small animal imaging techniques (SPEC CT and PET scan).

Clinical trials in Idiopathic Pulmonary Fibrosis patients and evaluation of biomarkers for chronic lung diseases.

Our lab investigates the pathophysiology of blood clotting disorders, and are currently focused on two diseases. Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, and is caused by defects in von Willebrand Factor that disrupt its ability to recruit platelets to sites of blood vessel damage. Thrombotic thrombocytopenic purpura (TTP) is a thrombotic disorder caused by acquired or inherited deficiency in the protease ADAMTS13. Current projects seek to understand (a) genetic variation in VWD and TTP and (b) the structure/function of ADAMTS13 and von Willebrand factor.

Key areas  

• High throughput mutagenesis screens
• Identification of novel protease substrates
• Role of proteases in bleeding disorders and cardiovascular disease

We use conventional techniques in biochemistry and molecular biology as well as high throughput sequencing, mass spectometry, and genome editing.

My primary research focus is improving the non-invasive diagnosis of gynecologic pathology, particularly those that cause pelvic pain, infertility, and reduced quality of life in women and those born with female pelvic organs. Non-invasive diagnoses can be achieved by a single tool such as ultrasound or a combination of tools such as biomarkers and clinical history. The longterm goal is to reduce the necessity for diagnostic laparoscopy and reliance on a purely clinical diagnosis for gynecologic pathologies. Secondarily, improved diagnosis may allow for more appropriately targeted therapies and proper evaluation of disease progression, which are areas of academic interest for me.

Specific to endometriosis, there are about a million unanswered questions. Areas I have started to explore included the microbiome, general population and obstetrician/gynecologist awareness of diagnostic techniques, machine learning models for diagnosis using ultrasound, diagnostic accuracy of advanced ultrasound techniques. Areas I am keen to explore are how the diagnosis of endometriosis impacts wellbeing and physical outcomes, how novel techniques can be disseminated outside of academic centres, how we can sample and test bodily fluids for biomarkers to assist in diagnosis and monitoring of disease state. Other possible considerations include the effect of complementary and alternative management strategies (e.g. physiotherapy, medical cannabis, psychotherapy) on endometriosis outcomes, optimizing evidence-based practices in endometriosis and infertility, and interventional trials on specific medical or surgical management options.

Research in the Liaw Lab focuses on the biological crosstalk between blood clotting, inflammation, and the immune system, a process termed “immunothrombosis”.   Specifically, we focus on the pathophysiology of venous thromboembolism (VTE), disseminated intravascular coagulation (DIC), as well as sepsis (including patients with COVID-19 infections).  Our integrative research approach includes studies at the levels of cell biology, biochemistry, animal models, and clinical studies of ICU patients.

Learn more about the Liaw  Lab: https://taari.mcmaster.ca/labs/liaw-lab/

Dr. Katherine Morrison is Co-Director of the Centre for Metabolism, Obesity and Diabetes Research (MODR) and a Professor in the Department of Pediatrics at McMaster University. The newly developed Centre focuses on translational aspects of research at the interface of preclinical and clinical research. She is a clinician researcher, active clinically in the Pediatric Weight Management and Pediatric Lipid Clinics at McMaster Children’s Hospital where she is the medical director. Her research is focused on the etiology, consequences and treatment of obesity and lipid disorders in children. She leads a CIHR funded, Canadian multi-site study examining the influence of pediatric weight management programs on health outcomes in children with obesity and is co-PI on a CIHR-funded team grant seeking new pathways important to the development of obesity and its comorbidities. She led the pediatric aspects of the Canadian Clinical Practice Guideline for the Prevention and Treatment of Obesity and is on the steering committee for the current work to update those guidelines. She is on the Advisory Board for the Ontario Pediatric Bariatric Network and co-leads the Working Group on Outcome Measurement. Dr. Morrison is dedicated to improving the health of Canadian children through research, improved clinical care and education.

The focus of our research is to understand how viruses evade host immune defenses. When a virus infects a host, the host mounts an impressive immune response aimed at preventing the virus from multiplying and spreading. Viruses have evolved strategies to block this response in order to ensure their survival. Probably the most important aspect of the host immune response to virus infection is the production of an immune modulator called interferon. Interferon has a great impact on host defense mechanisms and as a result viruses have evolved multiple strategies to overcome its activities. We are currently studying the mechanisms of interferon inhibition and the countermeasures taken by different viruses.
These studies have led us to developing viruses for use in gene therapy and cancer therapy. The virus that we focus on is herpes simplex virus type 1 (HSV-1) which is a human pathogen that causes cold sores. We have found that by disabling the virus through removal of particular genes, the virus can grow in cancer cells and kill these cells while having no effect on healthy cells. Such viruses, called “oncolytic viruses” are currently being tested as a novel approach to cancer therapy in the hopes of eliminating tumors without the toxic side effects associated with many current treatments. HSV-1 is also being studied as a tool for gene therapy, since it is easy to manipulate, it can be targeted to specific tissues and it can house several therapeutic genes in a single vector. Thus, overall, our goal is to understand how viruses and their hosts interact with each other so that we can use viruses as tools for the treatment of multiple diseases

https://www.mossmanlab.com

Dr. Mukherjee is an Assistant Professor in the Division of Respirology, Department of Medicine, and a translational scientist affiliated with the Research Institute of St. Joe’s, Hamilton. She has demonstrated expertise in investigating inflammatory mechanisms of chronic respiratory diseases, in particular autoimmunity, response to treatment, and development/ validation of clinical biomarkers. Her research has identified the presence of localized autoimmune responses in the airways of patients with complex airways disease and determined their pathogenic role in driving disease severity. Of recent, she has identified autoimmune responses in acute-severe COVID and linked autoimmunity with post-acute COVID-19 sequelae (or Long COVID). Dr. Mukherjee’s research program focuses on “Lung autoimmunity and biomarkers”. She is the past recipient of the Emerging Researcher Award in Allergic Asthma awarded conjointly by the Canadian Institutes of Health Research (CIHR) and the Canadian Asthma, Allergy and Immunology Foundation (CAAIF). Her lab is funded by federal and non-federal sources including CIHR-ICRH and industry. Dr Mukherjee was recently named the AstraZeneca Chair in Respiratory Diseases (2023-2028). Current ongoing projects span from investigating mechanisms of disease to validating biomarkers in asthma, eGPA, COVID-19 and lung cancer.

Research Interests

1. Autoimmunity in complex airway diseases

2. Development of biomarkers for optimal management of complex airway diseases

3. Long COVID and autoimmunity

Dr. Nair’s research focuses on developing and applying novel sputum biomarkers and bio-imaging techniques to treat patients with coplex airway diseases such as severe asthma, COPD, bronchiolitis, EGPA, and other eosinophilic lung disorders.

My research interests are in the specific interactions between antibodies and their target antigens on platelets, leading to thrombocytopenia and/or thrombosis. Heparin induced thrombocytopenia and Immune thrombocytopenia (ITP) are great models for identifying key factors involved in the pathogenesis of the immune responses leading to low platelet counts. Our research focuses on the cellular and humoral immunity and the downstream effects on platelet physiology. We use our research to identify the pathology from patient samples and create in-vitro models that could explain our findings and further our understanding of the issues at hand.

Our translational research capitalizes on technologies in the fields of immunology, biochemistry, and molecular biology to transfer basic science findings to the clinical practice for improved patient care. Our in-vitro human megakaryocytopoiesis/thrombopoiesis model serves as a benchmark for studying intrinsic and extrinsic factors that affect platelet production. The manipulation of various conditions in this in-vitro model provides avenues to study the pathologies associated with diseases such as ITP.

Dr. Joyce Obeid is an Assistant Professor with the Child Health & Exercise Medicine Program, Department of Pediatrics at McMaster University. Her research focuses on exploring the power of play for children and adolescents growing up with a chronic medical condition or disability.

Dr. Obeid completed her PhD under the supervision of Dr. Brian Timmons in July 2015. Her PhD was entitled “Circulating progenitor and endothelial cells in healthy children and children with juvenile idiopathic arthritis: role of fitness, physical activity, and acute exercise.” Dr. Obeid was funded by a CIHR Banting & Best Scholarship during her doctoral studies. She then completed a Postdoctoral Fellowship with Dr. Timmons (2015-2017) investigating the relationship between fitness, physical activity, inflammation and cardiovascular health in children with chronic inflammatory disease.

Dr. Obeid’s current research spans 3 broad and connected themes, including exploring the measurement of movement, understanding the relationships between physical activity and health, and investigating the role of technology to promote physical activity across the pediatric years.

Research interests in the genetic and molecular epidemiology of cardiovascular disease.

My laboratory is involved in collaborative works to identify and characterize genetic and molecular markers of cardiovascular disease. One project aims to find genetic determinants of stroke. Another project is looking into novel lipid markers of myocardial infarction. A third project investigates the pharmacogenetic determinants of drugs commonly used for cardiovascular disease treatment and prevention. Finally, a last project consists in developing novel statistical methods to detect gene-gene and gene-environment interactions.

Dr. Pinto-Sanchez is currently an active medical staff at the Gastroenterology Division at McMaster University and Hamilton Health Sciences where she provides consultation services in the area of gastroenterology and Nutrition. She is the Director of the Celiac Clinic at McMaster University and provides nutrition support for the Home Parenteral Nutrition program and Intestinal failure clinic. Her clinical and research interest include the diagnosis and treatment of different gastrointestinal conditions, with focus on celiac disease and gluten related disorders.

The major focus of my research is on inborn errors of metabolism/biochemical genetics. This encompasses clinical research in the treatment of these disorders and the development of diagnostic tests, particularly the development and clinical validation of mass-spectrometry based assays.

I spend most of my clinical time in the area of biochemical genetics, either running Metabolic Genetic clinics at McMaster Children’s Hospital, or directing the Biochemical Genetics Laboratory at the Hamilton Regional Laboratory Medicine Program. I am also head of the regional newborn screening follow-up program and member of the Newborn Screening Ontario Advisory Council.

Academic Interests

I primarily teach post-graduate trainees in laboratory medicine and pediatrics residency and fellowship programs. I am also an active member of the national governing bodies for medical biochemistry (Royal College of Physicians and Surgeons of Canada) and biochemical genetics (Canadian College of Medical Geneticists).

The programing of disease can be initiated in utero. The placenta, which is the only fully functional yet disposable organ, plays a central role in dictating the levels of nutrients, oxygen and regulatory growth signals available to the developing fetus. External insults, such as a high fat diet, or exposure to drugs during pregnancy can alter the function of the stem cells within the placenta. This can lead to poor metabolic “programming” of the fetus and contribute to life long health complication for the offspring.

My lab focuses on understanding how these external insults change the function of the stem cells within the placenta, referred to as trophoblasts. Specifically we focus on understanding the link between the changes in the function of these cells with the altered development of fetus. Using a rodent model of diet induced obesity, we have already demonstrated that the high fat diet induced changes in these cells can alter the development of the placenta and dramatically affect the survival of the fetus. Furthermore, we are interested in exploring how metabolic changes in the trophoblasts can lead to excessive production of free radicals within the placenta. Balanced free radical signaling is very important for good placental health. Since the placenta behaves like a tumor, many of the signaling pathways that we explore are paralleled in cancer biology.

By understanding, more clearly, the pathways that involved in linking maternal uterine stressors and fetal growth and survival we hope to develop therapeutic strategies which may target the very origins of disease. Improving “placental health” will impact a number of diseases such as obesity, type 2 diabetes and cardiovascular disease. All of these conditions have been demonstrated to have a strong association with in utero programing.

We utilize both cell culture and animal models to understand these processes and develop therapeutic strategies to minimizing the consequences of in utero stress on neonatal health. The range of techniques applied in my laboratory spans molecular approaches (advanced proteomics, RT-PCR, determination of DNA methylation patterns) to cellular (immunological approaches to determining protein expression, enzyme assays, live-cell microscopy; electron microscopy) to physiological methods (evaluation of blood pressure in rodents, determination of glucose tolerance, histology, immunochemistry). In association with clinical collaborators, the scope of the research in my group spans from molecules to humans.

In addition to the biomedical research in my laboratory, I am also the Co-founder of the McMaster Children’s and Youth University. This is a program that mentors undergraduates and graduate students in multidisciplinary science outreach aimed at middle school age youth. This unique skill set, which is quite different from the science communication taught in the research laboratory, provides connections to post-graduate employment opportunities. Additional information about my research program and Children’s Universities educational outreach opportunities can be found on my laboratory web-site: Raha Lab.

Investigations of normal and abnormal development of the extrinsic innervation of the gut

My research is focused on determining how, during ontogeny, vagal and sacral nerves find their targets in the bowel and on examining whether developmental abnormalities of this innervation contribute to the pathogenesis of disorders of gastrointestinal motility.

Experiments in tissue culture involve maintenance of cell lines and primary cultures of explanted tissue. Animal work includes in-bred strains and several lines of transgenic mice. I am a member of the Farncombe Family Digestive Health Research Institute and collaborate with members of the Brain-Body Institute (BBI).

We are expanding upon our discovery that extracellular non-adenine based purines stimulate cell differentiation, regeneration and prevent cell death; identifying receptors and signalling cascades and applying these to medically-relevant systems, including brain and spinal injury, wound healing and neuroprotection. We also study the interactions of non-adenine based purines and protein cell growth factors.

In related studies, we have discovered that glia from the enteric nervous system enhance regeneration of damaged axons through the central nervous system. We are studying the mechanisms involved and attempting to further facilitate functional regeneration after spinal cord injury.

A wide spectrum of techniques including biochemistry, cell and molecular biology, in vivo studies, cell culture, histology, immunohistochemistry and electron microscopy. Collaboration with several groups in Canada, North and South America, Europe and Asia, increases the breadth of approaches used.

Our laboratory is investigating the cellular and molecular mechanisms of chronic inflammation, with applications to joint disease (Rheumatoid Arthritis), lung disease (asthma and pulmonary fibrosis) and cardiovascular disease (atherosclerosis). We run a variety of projects that focus on certain ligands, their cell-receptor complexes, cell signalling and gene regulation in tissues/cells relevant for each of these inflammatory conditions. We have a number of local and international collaborations that are geared to specific aspects of the projects.

We explore receptor regulation, cell signal pathways, mesenchymal precursor cell differentiation and regulation of inflammation in models in vivo, particularly in response to the gp130 class of cytokines. We utilize Adenovirus vector systems to over-express cytokines in tissues in vitro and in vivo, and examine inflammation in gene-targetted mutant mice, with the goal of developing effective approaches to treat conditions in joint, lung and cardiovascular inflammatory diseases.

Our laboratory is investigating innate and adaptive mucosal immune responses against viral infections and the development of safe and effective mucosal vaccines to protect against infections, especially by sexually-transmitted viruses, such as herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1). We are focussing on the mechanisms by which mucosal vaccines protect against intravaginal virus challenge. Additionally, we are studying the ability of innate immune activators or “Danger Signals”, such as CpG DNA, to serve as mucosal vaccine adjuvants or to act on their own to protect against mucosal/genital viral infection.

Methodology includes a variety of virologic, immunologic and molecular techniques, including murine and human cell culture, lymphocyte isolation, FACS analysis, CTL assays, recombinant viral vector construction, virus neutralization assays, ELISA and ELISPOT assays.

Pediatric Diabetes, Translational Research, Child Health, Metabolism, Inflammation, Immunometabolism, Pediatric Obesity, Knowledge Synthesis, Knowledge Translation

Dr. M. Constantine Samaan is a staff physician in the division of Pediatric Endocrinology and Associate Professor in the Department of Pediatrics at McMaster University and McMaster Children’s Hospital.
Dr. Samaan’s research program is in the area of translational research, with specific focus on pediatric diabetes.

Goals of Dr. Samaan’s research program:
The specific focus of Dr. Samaan’s program of research include the following platforms
1. Investigate the determinants of diabetes in at-risk populations
2. Evaluation of interventions to manage diabetes in children
3. Knowledge Translation (KT) through the conduct of systematic reviews and meta-analysis

This bedside-to-bench side approach to research allows the comprehensive study of the drivers of pediatric diabetes, and the evaluation of specific therapeutic and preventative strategies for diabetes.

The clinical studies focus on understanding what keeps children healthy, and what environmental and psychosocial factors increase the risk of diabetes. We work with several pediatric populations who already have or at risk of developing diabetes.
The bench studies use a state-of-the-art molecular and cell biology platforms to define mechanisms responsible for the development of diabetes. An important component of this platform is the investigation of the role of immune system activation and inflammation in driving diabetes in children and across the lifespan.

Dr. Zainab (Zena) Samaan is an Associate Professor, Department of Psychiatry and Behavioral Neurosciences, Associate Member, Department of Clinical Epidemiology and Biostatistics and Associate Faculty, Population Genomics Program, McMaster University. Dr. Samaan is also a staff psychiatrist, member of the Royal College of Psychiatrists, UK and Certified Academic Psychiatrist by The College of Physicians and Surgeons of Ontario. Dr. Samaan completed a Master’s in Science at the Dept. of Psychiatry, Trinity College Dublin, Ireland and further trained in psychiatric genetic epidemiology with Professors Peter McGuffin and Anne Farmer at the Institute of Psychiatry and Maudsley Hospital, London, UK where she obtained PhD in psychiatric genetics. Dr. Samaan is also a Staff Psychiatrist at St. Joseph’s Healthcare and Hamilton Health Sciences.

Her clinical interests are centered on the interface between psychiatry and medicine specifically, depression comorbidity with obesity and cardiovascular disease.

My research focuses on cellular mechanisms of inflammatory diseases of the upper and lower airways including asthma, allergic rhinitis and COPD. We investigate the role of alarmins, lipid mediators and cytokines in promoting migrational responses of mature eosinophils and their progenitor cells. A major focus of my work has been investigating the role of local tissue differentiative processes in the development of eosinophilic inflammation. We have methodologies for comprehensive enumeration and phenotypic analyses of rare cells including eosinophil-lineage committed progenitor cells, basophils, lymphocytes and group 2 innate lymphoid cells to better understand the interaction between innate and adaptive immune cells in asthmatic inflammatory responses. The ability to sample sputum, blood and bone marrow extracted cells from the same subject has helped to investigate the cross-compartmental effects of biologics and develop an in-depth understanding of the mechanistic effects of these therapies in mild and severe asthma.

I participate in undergraduate and graduate courses including Demystifying Medicine, Pathobiology of Airways Diseases and Research Methodology. I have published over 90 peer-reviewed articles and book chapters and continues to supervise both undergraduate and graduate students and post-doctoral fellows.

Our research focuses on two areas: natural and recombinant coagulation proteins that either stimulate or suppress coagulation; and the modification of the in vivo clearance of therapeutic proteins. Expanding areas of interest include phage display and DNA and RNA aptamer library screening to generate novel antithrombotic agents.

A variety of biochemical and molecular biological approaches are used, including site-directed and PCR-based mutagenesis, expression of recombinant proteins in bacterial, yeast, or cultured mammalian cell systems, protein characterization using enzymatic, immunochemical, biochemical, and thromboelastographic techniques, and in vivo studies of protein clearance and function in mice.

The Sloboda Lab interests are founded in the early life origins of health and disease. We are interested in understanding the impact of early life adversity on the mother, and the developing fetus and how fetal adaptations to adversity influence the risk of chronic disease later in life. Our experimental studies investigate the effects of early life nutritional or endocrine stress on maternal, fetal and placental development.

Dr. Steinberg is a professor of medicine at McMaster University where he holds a Canada Research Chair and a J. Bruce Duncan Endowed Chair in Metabolic Diseases and is Co-Director of the Centre for Metabolism, Obesity and Diabetes Research. https://healthsci.mcmaster.ca/metabolism-research

His research studies cellular energy sensing mechanisms and how endocrine factors, lipid metabolism and insulin sensitivity are linked and contribute to the development of obesity, type 2 diabetes, cardiovascular disease and cancer. He has published over 180 papers many in leading scientific journals. His scientific contributions have been recognized by the Endocrine Society, the American Diabetes Association, Diabetes Canada and the Canadian Institutes of Health Research who have each presented him with early career outstanding scientific achievement awards.

Dr Svenningsen is a translational pulmonary imaging scientist, her research program focuses on the development and clinical study of non-invasive pulmonary computed tomography (CT)and magnetic resonance imaging (MRI) measurements that are highly sensitive to pathological changes in the airways and lung parenchyma. To improve pulmonary disease outcomes, Dr Svenningsen’s research program focus on three translational themes using an integrated clinical and medical imaging approach: translational imaging to (1) detect and understand the early manifestation of pulmonary diseases, (2) predict and evaluate pulmonary disease outcomes, and (3) improve the selection, delivery and efficacy of therapies targeting pulmonary diseases.

Down-regulation of programd cell death (apoptosis) and functional inactivation of tumor suppressors are the rate limited steps towards tumorigenesis. Enhancing survival functions by amplification of Bcl-2, PI-3 kinase, Protein kinase B (PKB/AKT) to repress apoptosis occurs in many human cancers. Functional inactivation of tumor suppressors, like p53, pTEN, and p14ARF takes place with high frequency (35-50%) in human tumors of the endometrium, brain, prostate, and others.

Approaches of genetics, molecular biology, cellular biology, and biochemistry are explored to address the above questions, including generation of stable or inducible cell lines using plasmid and retrovirus, detection of protein-protein interaction and cell cycle progression.

The overall theme of our research is an evaluation of treatment strategies to attenuate the effect of neuromuscular disorders and aging on skeletal muscle function.

Currently, we are looking at a number of nutritional and exercise interventions to enhance muscle function in response to neuromuscular, neurometabolic disorders as well as in the aging process. We have transgenic animal models of several neuromuscular disorders and are also completing clinical trials in patients with these conditions. Another line of research is the role of mitochondria in aging and the role of oxidative stress/apoptosis in skeletal muscle damage in response to exercise and neuromuscular disorders.

We use a variety of methods in the laboratory from strength and functional outcome measures in the dry laboratory to Western blotting, RT-PCR, PCR, enzyme analysis, metabolite analysis, ELISA, microscopy (immuno, EM and fluorescent methods), GC-MS, micro array, HPLC and RIA.

Dr. Brian Timmons is the Canada Research Chair in Child Health & Exercise Medicine, and Associate Professor of Pediatrics at McMaster University. He is Research Director and Clinical Development Lead of the Child Health & Exercise Medicine Program, Associate Member in the Department of Kinesiology and Offord Centre for Child Studies, and Scientist with CanChild Centre for Childhood Disability Research. Brian’s research program examines 3 inter-related themes: translational science, clinical innovation, and public health, using a lab bench to park bench approach to study the role of exercise as medicine for children and youth.

The Child Health & Exercise Medicine Program encompasses research, education, and clinical components. Integration of these 3 pillars makes the program unique in the world. The diversity of the Child Health & Exercise Medicine program creates a rich training environment. Students and trainees are exposed to a combination of clinical research methods and basic science techniques. Exercise laboratory protocols include cycle ergometry, indirect calorimetry, and spirometry. We use accelerometry to measure physical activity. ELISA, cell isolation and flow cytometry, metabolite analysis and stable isotope methods are also used in our studies.

Students and trainees at CHEM are exposed to a unique combination of clinical research methods and basic science techniques. Exercise laboratory protocols include cycle ergometry, indirect calorimetry, and spirometry. We rely heavily on accelerometry to measure free living physical activity in healthy children and in children with a chronic disease. ELISA, cell isolation and flow cytometry, metabolite analysis and stable isotope methods are also used in many of our studies.

Atherosclerosis is a major cause of heart disease and stroke, among the leading causes of hospitalization and death in Western countries. It is a multifactorial disease involving a variety of physiological pathways. These include innate immunity, inflammation and lipoprotein metabolism.

Our laboratory utilizes mouse molecular genetics to delineate the contribution of components of these pathways to the development of atherosclerosis. The mouse has been an extremely useful model genetic system to analyze pathways involved in atherosclerosis. In conventional mouse models of atherosclerosis, including the workhorse apoE and LDL receptor knockout mouse strains, atherosclerosis develops primarily in the aorta while coronary arteries, which feed the heart, appear resistant to disease. In contrast, mice that lack a receptor for high density lipoproteins develop extensive atherosclerosis in their coronary arteries as well as increased atherosclerosis in their aortas. These mice develop myocardial infarction as a result of the extensive coronary artery atherosclerosis. This suggests that the HDL receptor, called SR-BI, plays a key role in protection against coronary artery atherosclerosis. One of the main focuses of the lab is to delineate the mechanisms by which expression of SR-BI in bone marrow derived cells including macrophages, protects against atherosclerosis. In particular, we are interested in understanding the role of this receptor in lipid transport as well as cell signalling.

We are also making use of our mouse models of coronary artery atherosclerosis to delineate the factors that normally contribute to the resistance of mouse coronary arteries to atherosclerosis development, as well as to test the contribution of different physiological pathways to the development of coronary artery atherosclerosis and myocardial infarction.

• dentification of cancer biomarkers predicting tumor response to radiotherapy and chemotherapy in lung and prostate cancer.
• Establishment of in-vitro and in-vivo models of lung and prostate cancer
• Translational studies of investigational new cancer therapies
• Investigation of novel radiation sensitizers

Current methodologies:

Clinical studies: We investigate EGFR, Erk, Akt, Stat3 and p38 MAPK expression in tumors of locally advanced NSCLC patients and examine their relationship with tumor response to radiation and with overall survival.

Laboratory studies: Lovastatin and polyphenol action is investigated in lung and prostate cancer cells in culture and in animals transplanted with tumors using advanced cell and molecular biology techniques. Signal transduction pathways activated by radiation and growth factors are examined at the protein and gene level and proliferation, cell cycle progression and apoptosis are investigated with immunoblotting, northern blotting and RT-PCR, colony forming and flow cytometry and fluorescence microcopy techniques.

I have had a longstanding interest in microbial commensal influence on chronic inflammatory disorders, long before the topic gained center stage in gastroenterology. After completing my MD studies in Buenos Aires, Argentina, I began clinical research training on Helicobacter pylori infection and chronic gastritis at the University of Lausanne, Switzerland. This was followed by a Ph.D. degree at the Institute of Microbiology and Gnotobiology of the Czech Academy of Science on the effect of commensal bacterial antigens in animal models of inflammatory bowel disease and celiac disease. As a post-doctoral fellow at McMaster University, I focused on beneficial (probiotic) bacteria and their effect on gut function and inflammation. As faculty at McMaster University, I developed a program to investigate host-microbial and dietary interactions in the gastrointestinal tract. In particular, I am interested in the role microbial factors play in modulating immune responses in the context of chronic intestinal conditions such as inflammatory bowel disease and celiac disease. Mechanistically, I focus on commensal and opportunistic pathogen metabolism and proteolytic activity, with the long-term objective to develop therapies to prevent or treat chronic inflammatory and autoimmune conditions.

Increasing Awareness of Celiac Disease

Verdu Lab Website

Small animal handling, bone marrow and lymphocyte isolation, Flow cytometry, cytotoxic T lymphocyte assays, immunohistochemistry, construction and application of viral vectors.

Research is focused on the molecular mechanisms of coagulation and fibrinolysis with emphasis on the clinical significance of findings.

Light scattering, fluorescence spectroscopy, and plasmon resonance are employed to study protein/protein, protein/carbohydrate or protein/DNA interactions. Kinetic analyses are used to examine rates of enzyme inactivation, whereas molecular biologic techniques (site-directed mutagenesis and expression of recombinant proteins in bacterial or cultured mammalian cell systems) are used to investigate structure-activity relationships of clotting enzymes and inhibitors. Hypotheses that originate from the results of basic research are then tested in animal models of arterial and venous thrombosis or in humans.

Our research is concentrated upon understanding why people with diabetes mellitus are predisposed to cardiovascular disease.

The last few decades have witnessed a dramatic, worldwide increase in the prevalence of diabetes mellitus. Complications associated with diabetes make it a leading cause of blindness, renal failure and lower limb amputations in adults as well as an important, independent risk factor for atherosclerotic cardiovascular disease (CVD). In fact, CVD accounts for over 65% of diabetic mortality. The treatment and prevention of diabetic complications such as CVD is currently limited by our lack of understanding of the mechanisms by which diabetes promotes atherosclerosis – the underlying cause of CVD.

The Werstuck laboratory is located at the Thrombosis and Atherosclerosis Research Institute (TAARI), a facility dedicated to basic, clinical, and epidemiologic research in thrombosis, atherosclerosis, and cardiovascular disease. Our research is focused upon delineating the mechanisms by which diabetes mellitus promotes the progression and development of atherosclerosis. Our laboratory employs a broad range of molecular and cellular techniques to examine cell and tissue-specific responses that are relevant to disease progression.

Research in the Werstuck lab is funded by operating grants from the Canadian Institutes of Health Research (CIHR), the Heart and Stroke Foundation of Canada (HSFC), and the Canadian Diabetes Association (CDA).

The general objective of my research program is to identify the genes and molecular mechanisms involved in development and differentiation of the eye, and further determine how these mechanisms may be perturbed in blinding ocular disease.

Methodologies include genetically targeted approaches in mice (transgenics, conditional mutants; null mutants), analyses of phenotypes using molecular and immunohistochemical approaches and cell culture models. We predict that these studies will lead to therapeutic strategies (via vitreal implants or gene therapy approaches) for correcting or preventing vision loss.

These research directions are being pursued both in animal models and human trials.