Research

• Microbiological biochemistry
• Antimicrobial research

Our lab studies enzymatic transition states. Enzymes catalyze reactions by binding more tightly to their transition states than anything else, up to 1,020 times tighter than their substrates or products. Once we have solved a transition state structure, we can design stable molecules that mimic its charge and shape and thus create powerful inhibitors. Enzymes perform all the chemical reactions that make life possible, which makes them interesting in their own right. There are also a lot of good reasons to inhibit enzymes, such as killing pathogenic bacteria with new antibiotics.

Research

• Microbiological biochemistry
• Antimicrobial research

Our lab studies enzymatic transition states. Enzymes catalyze reactions by binding more tightly to their transition states than anything else, up to 1,020 times tighter than their substrates or products. Once we have solved a transition state structure, we can design stable molecules that mimic its charge and shape and thus create powerful inhibitors. Enzymes perform all the chemical reactions that make life possible, which makes them interesting in their own right. There are also a lot of good reasons to inhibit enzymes, such as killing pathogenic bacteria with new antibiotics.

Research

• Molecular biophysics

I am interested in studying the dynamics of single molecules inside biological systems using optical tools. Dynamics is essential to the survival of the cell, which is a biological unit in permanent evolution and which has to be able to process and react to information. Dynamical processes inside the cell happen on a very wide range of length and time-scales and are governed by complex and intricate rules and mechanisms. At the scale of the molecule, they are of interest for the physicist as well as for the biologist, since they involve basic transformation of chemical or thermal energy into mechanical energy. In order to unravel their exact mechanisms, in vivo quantitative measurements at the single molecule level are required, which recent developments in the domain of fluorescence techniques, single molecule detection and recombinant protein technology now offers the possibility to do.

Research

• Molecular biophysics

I am interested in studying the dynamics of single molecules inside biological systems using optical tools. Dynamics is essential to the survival of the cell, which is a biological unit in permanent evolution and which has to be able to process and react to information. Dynamical processes inside the cell happen on a very wide range of length and time-scales and are governed by complex and intricate rules and mechanisms. At the scale of the molecule, they are of interest for the physicist as well as for the biologist, since they involve basic transformation of chemical or thermal energy into mechanical energy. In order to unravel their exact mechanisms, in vivo quantitative measurements at the single molecule level are required, which recent developments in the domain of fluorescence techniques, single molecule detection and recombinant protein technology now offers the possibility to do.

Research

• Biophysics
• Bioinformatics

I started out as a statistical physicist working on polymers and soft condensed matter. I became interested in applications of statistical mechanics to biological problems. This led me to study RNA folding and various problems in population genetics and evolutionary biology. In recent years I have been working in bioinformatics and molecular evolution.

Research

• Biophysics
• Bioinformatics

I started out as a statistical physicist working on polymers and soft condensed matter. I became interested in applications of statistical mechanics to biological problems. This led me to study RNA folding and various problems in population genetics and evolutionary biology. In recent years I have been working in bioinformatics and molecular evolution.

Research

• Biological NMR
• Protein structure and dynamics
• Biomolecular interactions
• Structural genomics

We are primarily interested in two main fields of research: the allosteric conformational switches that control signaling pathways and the early steps of amyloid fibril formation. Allosteric conformational switches in signaling pathways: we are currently mapping the intra-molecular signaling pathways and the dynamic changes that propagate the signal carried by second messengers. So far, our work has focused mainly on the prototypical receptor for cAMP (i.e., protein kinase A) and, specifically, on a single cAMP-binding domain of PKA that controls the inhibition of PKA in a cAMP-dependent manner. Early steps of amyloid fibril formation: we are currently investigating the mechanism of nucleation and of inhibition of amyloid fibrils. So far, our work in this field has mainly focused on the Ab system and on endogenous proteins that inhibit its pathogenic oligomerization.

Research

• Biological NMR
• Protein structure and dynamics
• Biomolecular interactions
• Structural genomics

We are primarily interested in two main fields of research: the allosteric conformational switches that control signaling pathways and the early steps of amyloid fibril formation. Allosteric conformational switches in signaling pathways: we are currently mapping the intra-molecular signaling pathways and the dynamic changes that propagate the signal carried by second messengers. So far, our work has focused mainly on the prototypical receptor for cAMP (i.e., protein kinase A) and, specifically, on a single cAMP-binding domain of PKA that controls the inhibition of PKA in a cAMP-dependent manner. Early steps of amyloid fibril formation: we are currently investigating the mechanism of nucleation and of inhibition of amyloid fibrils. So far, our work in this field has mainly focused on the Ab system and on endogenous proteins that inhibit its pathogenic oligomerization.

Research

Dr. Nazy’s research interests include: translational research in immuno-hematology, cellular and humoral mechanisms of disease, drug discovery, translation of basic science findings to clinical applications, heparin-induced and immune thrombocytopenia and platelet disorders. Specifically, Ishac’s interests lie in the specific interactions between antibodies and their target platelet-related antigens, leading to thrombocytopenia and thrombosis. Heparin induced thrombocytopenia and Immune thrombocytopenia are great models for identifying key factors involved in the pathogenesis of the immune response leading to low platelet counts. His research focuses on the cellular and humoral immunity and the downstream effects of antibody production on platelet physiology. He uses his research to identify the pathology from patient samples and create in vitro models that could explain his findings and further his understanding of the issues at hand.

Research

Dr. Nazy’s research interests include: translational research in immuno-hematology, cellular and humoral mechanisms of disease, drug discovery, translation of basic science findings to clinical applications, heparin-induced and immune thrombocytopenia and platelet disorders. Specifically, Ishac’s interests lie in the specific interactions between antibodies and their target platelet-related antigens, leading to thrombocytopenia and thrombosis. Heparin induced thrombocytopenia and Immune thrombocytopenia are great models for identifying key factors involved in the pathogenesis of the immune response leading to low platelet counts. His research focuses on the cellular and humoral immunity and the downstream effects of antibody production on platelet physiology. He uses his research to identify the pathology from patient samples and create in vitro models that could explain his findings and further his understanding of the issues at hand.

Research

I am a molecular evolutionary geneticist and biological anthropologist by training and rely heavily on interdisciplinary research. I use both chemical and molecular techniques to elucidate the state of preservation within forensic, archeological and paleontological remains. This information is subsequently used to devise novel techniques to extract the molecular information (DNA and/or protein sequences) which is then used to address evolutionary and anthropological questions, such as the “relatedness” of Archaic humans and Neanderthals from a genetic standpoint, sex and diet from prehistoric Native Amerindian hunter-gatherer populations using coprolites samples, and the timing and origin of HIV using archival blood and brain tissue samples.

Dr. Poinar is currently looking for valuable biochemistry students, if you are interested please email him.

Research

I am a molecular evolutionary geneticist and biological anthropologist by training and rely heavily on interdisciplinary research. I use both chemical and molecular techniques to elucidate the state of preservation within forensic, archeological and paleontological remains. This information is subsequently used to devise novel techniques to extract the molecular information (DNA and/or protein sequences) which is then used to address evolutionary and anthropological questions, such as the “relatedness” of Archaic humans and Neanderthals from a genetic standpoint, sex and diet from prehistoric Native Amerindian hunter-gatherer populations using coprolites samples, and the timing and origin of HIV using archival blood and brain tissue samples.

Dr. Poinar is currently looking for valuable biochemistry students, if you are interested please email him.

Research

• Metabolism, obesity and Type 2 diabetes

Dr. Steinberg’s research involves understanding how hormones regulate the body’s storage and breakdown of fat and its response to insulin. He is conducting metabolic studies in which genetically modified mice exercise or consume calorie foods. How many and what type of calories (fat or carbohydrate) the mice burn will be measured both during exercise and in response to hormones. Steinberg’s studies will be complemented with work using advanced techniques in protein chemistry and molecular biology with an emphasis on phosphoproteomics (identifying, cataloguing and characterizing proteins) and gene expression analysis.

Research

• Metabolism, obesity and Type 2 diabetes

Dr. Steinberg’s research involves understanding how hormones regulate the body’s storage and breakdown of fat and its response to insulin. He is conducting metabolic studies in which genetically modified mice exercise or consume calorie foods. How many and what type of calories (fat or carbohydrate) the mice burn will be measured both during exercise and in response to hormones. Steinberg’s studies will be complemented with work using advanced techniques in protein chemistry and molecular biology with an emphasis on phosphoproteomics (identifying, cataloguing and characterizing proteins) and gene expression analysis.

Research

The Surette Laboratory’s primary area of research investigates the role of normal flora-pathogen interactions in health and disease in the area of respiratory infections with a focus in cystic fibrosis. A polymicrobial perspective on these infections has lead to identification of overlooked pathogens in airway disease, as well as synergistic interactions between avirulent organisms and pathogens. This is a fundamentally different view of airway infections and has lead to direct benefits to patients through altered treatment strategies.

Research

The Surette Laboratory’s primary area of research investigates the role of normal flora-pathogen interactions in health and disease in the area of respiratory infections with a focus in cystic fibrosis. A polymicrobial perspective on these infections has lead to identification of overlooked pathogens in airway disease, as well as synergistic interactions between avirulent organisms and pathogens. This is a fundamentally different view of airway infections and has lead to direct benefits to patients through altered treatment strategies.

RESEARCH

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.

RESEARCH

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.

Research

• Metabolism and toxicology

Nutritional biochemistry and applied nutrition related to skeletal development during growth and in pediatric diseases. Dr. Atkinson is a nutritional scientist whose research interests encompass studies of the nutritional and endocrine regulation of growth processes, with a focus on skeletal development. Her clinical research has identified abnormalities in growth and bone development associated with disease or drug (e.g., steroids) therapies in children with disorders such as prematurity, leukemia, cystic fibrosis or epilepsy. Studies in children and an animal model have investigated the potential of anabolic agents such as nutrition, calcitriol, growth hormone or insulin-like growth factor to preserve normal growth processes in target disease pediatric populations. Insights into the functional aspects of bone metabolism are assessed by bone histomorphometry, bone mass and body composition by dual energy x-ray absorptiometry, bone strength testing and measurements of bone bi markers such as osteocalcin, IGF-I, IGF binding protein and cross-linked C-telopeptide of type 1 collagen. Using standard and mini pigs as animal models, current research focuses on the mechanisms by which steroid drugs alter bone metabolism during early development and the potential for osteoanabolic agents such as recombinant growth factors such as (growth hormone or IGF-I), bisphosphate drugs or calcitriol to attenuate the catabolic effects of the steroids on normal bone growth. The long term objective of this area of research is to extend knowledge of how physiological mechanisms affecting mineral utilization change from infancy and throughout development, the impact of disease and drugs on these processes and possible nutritional or pharmacological interventions that will ameliorate any abnormalities that might impede a child’s genetic potential to achieve peak bone mass, a key factor in prevention of adult-onset osteoporosis.

Selected Publications

• Dexamethasone-induced abnormalities in growth and bone metabolism in piglets are partially attenuated by growth hormone with no synergistic effect of insulin-like growth factor-I. Ward, WE, Donovan, SM, Atkinson, SA. Pediatr Res 1998;44:215-221.
• Bone metabolism and circulating IGF-I and IGFBPs in dexamethasone-treated preterm infants. Ward WE, Atkinson SA, Donovan S, Paes B. Early Human Develop 1999; 56:127-141.
• Comparative response in growth and bone status to three dexamethasone treatment regimens in infant piglets. Guo, C-Y, Ward W, Cairns P, Atkinson SA Pediatr Res 2000;48:1-6.
• Calcium competes with zinc for a channel mechanism on the brush border membrane of piglet intestine. Bertolo RF, Bettger W, Atkinson S.A. J Nutr Biochem 2001;12(2):66-72.
• Elevated intact parathyroid hormone is associated with reduced bone resorption in infant piglets receiving oral dexamethasone for 15 days. Guo C-Y, Weiler H, Atkinson SA. J Biology of the Neonate 2001;80:195-199.
• Long term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Guo C-Y, Ronen GM, Atkinson SA Epilepsia 2001;42(9):1141-47.
• Hypomagnesemia associated with chemotherapy in children treated for acute lymphoblastic leukemia: possible mechanisms. Guo CY, Atkinson SA, Halton J, Barr RD. Oncology Reports 2003;10:In press.

Research

• Metabolism and toxicology

Nutritional biochemistry and applied nutrition related to skeletal development during growth and in pediatric diseases. Dr. Atkinson is a nutritional scientist whose research interests encompass studies of the nutritional and endocrine regulation of growth processes, with a focus on skeletal development. Her clinical research has identified abnormalities in growth and bone development associated with disease or drug (e.g., steroids) therapies in children with disorders such as prematurity, leukemia, cystic fibrosis or epilepsy. Studies in children and an animal model have investigated the potential of anabolic agents such as nutrition, calcitriol, growth hormone or insulin-like growth factor to preserve normal growth processes in target disease pediatric populations. Insights into the functional aspects of bone metabolism are assessed by bone histomorphometry, bone mass and body composition by dual energy x-ray absorptiometry, bone strength testing and measurements of bone bi markers such as osteocalcin, IGF-I, IGF binding protein and cross-linked C-telopeptide of type 1 collagen. Using standard and mini pigs as animal models, current research focuses on the mechanisms by which steroid drugs alter bone metabolism during early development and the potential for osteoanabolic agents such as recombinant growth factors such as (growth hormone or IGF-I), bisphosphate drugs or calcitriol to attenuate the catabolic effects of the steroids on normal bone growth. The long term objective of this area of research is to extend knowledge of how physiological mechanisms affecting mineral utilization change from infancy and throughout development, the impact of disease and drugs on these processes and possible nutritional or pharmacological interventions that will ameliorate any abnormalities that might impede a child’s genetic potential to achieve peak bone mass, a key factor in prevention of adult-onset osteoporosis.

Selected Publications

• Dexamethasone-induced abnormalities in growth and bone metabolism in piglets are partially attenuated by growth hormone with no synergistic effect of insulin-like growth factor-I. Ward, WE, Donovan, SM, Atkinson, SA. Pediatr Res 1998;44:215-221.
• Bone metabolism and circulating IGF-I and IGFBPs in dexamethasone-treated preterm infants. Ward WE, Atkinson SA, Donovan S, Paes B. Early Human Develop 1999; 56:127-141.
• Comparative response in growth and bone status to three dexamethasone treatment regimens in infant piglets. Guo, C-Y, Ward W, Cairns P, Atkinson SA Pediatr Res 2000;48:1-6.
• Calcium competes with zinc for a channel mechanism on the brush border membrane of piglet intestine. Bertolo RF, Bettger W, Atkinson S.A. J Nutr Biochem 2001;12(2):66-72.
• Elevated intact parathyroid hormone is associated with reduced bone resorption in infant piglets receiving oral dexamethasone for 15 days. Guo C-Y, Weiler H, Atkinson SA. J Biology of the Neonate 2001;80:195-199.
• Long term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy. Guo C-Y, Ronen GM, Atkinson SA Epilepsia 2001;42(9):1141-47.
• Hypomagnesemia associated with chemotherapy in children treated for acute lymphoblastic leukemia: possible mechanisms. Guo CY, Atkinson SA, Halton J, Barr RD. Oncology Reports 2003;10:In press.

Research

Dr. Berg’s research interests are focused around understanding determinants of treatment response in acute myeloid leukemia (AML) and to develop novel treatments based on this understanding. He is trained as a hematologist and medical oncologist. During his doctoral thesis and postdoctoral fellowship, he received additional training in molecular and cellular biology. Dr. Berg has been using functional model systems both in vitro and in vivo to study the role of epigenetic regulators in this context and their interplay with lineage-specific differentiation and more classical transcriptional regulators. His team also studies the biological processes that occur in residual cells after treatment to potentially explain why AML, unfortunately, often relapses after treatment. This effort is based on the combined use of Dr. Berg’s previous expertise in identifying minimal residual disease (MRD) in AML based on flow-cytometric techniques and the application of functional assays and novel single cell resolution methods to characterize residual AML cells during, and shortly after, chemotherapy in patients and surrogate xeongraft models. As a clinician scientist, Dr. Berg is actively involved in the clinical treatment of patients with hematological malignancies. His focus is in the fields of hematopoietic stem cell transplantation and early clinical trials. Allogeneic stem cell transplantation (transplantation with cells from related or unrelated donors) represents a platform technology for curing otherwise incurable hematological malignancies including leukemias at a high risk for relapse. His team plans to use MRD-guided interventions and combine the use of allogeneic stem cell transplantation with targeted therapies. With his background in early clinical trials, Dr. Berg is poised to facilitate the translation of findings into novel treatment

Research

Dr. Berg’s research interests are focused around understanding determinants of treatment response in acute myeloid leukemia (AML) and to develop novel treatments based on this understanding. He is trained as a hematologist and medical oncologist. During his doctoral thesis and postdoctoral fellowship, he received additional training in molecular and cellular biology. Dr. Berg has been using functional model systems both in vitro and in vivo to study the role of epigenetic regulators in this context and their interplay with lineage-specific differentiation and more classical transcriptional regulators. His team also studies the biological processes that occur in residual cells after treatment to potentially explain why AML, unfortunately, often relapses after treatment. This effort is based on the combined use of Dr. Berg’s previous expertise in identifying minimal residual disease (MRD) in AML based on flow-cytometric techniques and the application of functional assays and novel single cell resolution methods to characterize residual AML cells during, and shortly after, chemotherapy in patients and surrogate xeongraft models. As a clinician scientist, Dr. Berg is actively involved in the clinical treatment of patients with hematological malignancies. His focus is in the fields of hematopoietic stem cell transplantation and early clinical trials. Allogeneic stem cell transplantation (transplantation with cells from related or unrelated donors) represents a platform technology for curing otherwise incurable hematological malignancies including leukemias at a high risk for relapse. His team plans to use MRD-guided interventions and combine the use of allogeneic stem cell transplantation with targeted therapies. With his background in early clinical trials, Dr. Berg is poised to facilitate the translation of findings into novel treatment

Research

• Understanding the communication between gene-modified cells and the immune system
• Development of new gene therapies
• Anti-viral strategies and vaccines

Research

• Understanding the communication between gene-modified cells and the immune system
• Development of new gene therapies
• Anti-viral strategies and vaccines

Research

We work with Streptomyces bacteria, which are remarkably complicated microbes: they are multicellular, have different ‘tissue’ types and are little pharmaceutical factories – they make more than 2/3 of known antibiotics, along with chemotherapeutics, immunosuppressants, fungicides, anti-parasitic agents.

Our goals are three-fold:

• To understand the role played by cell surface proteins during the transition between different developmental stages.
• To understand how the chromosome is organized in the cell and how this organization contributes to antibiotic production. These studies will allow us to more effectively manipulate antibiotic production and stimulate the synthesis of new antibiotics.
• To understand the role of regulatory RNAs – and RNA metabolism – in controlling development and antibiotic production.

Research

We work with Streptomyces bacteria, which are remarkably complicated microbes: they are multicellular, have different ‘tissue’ types and are little pharmaceutical factories – they make more than 2/3 of known antibiotics, along with chemotherapeutics, immunosuppressants, fungicides, anti-parasitic agents.

Our goals are three-fold:

• To understand the role played by cell surface proteins during the transition between different developmental stages.
• To understand how the chromosome is organized in the cell and how this organization contributes to antibiotic production. These studies will allow us to more effectively manipulate antibiotic production and stimulate the synthesis of new antibiotics.
• To understand the role of regulatory RNAs – and RNA metabolism – in controlling development and antibiotic production.

Research

Dr. 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 fiber and primary myoblast cultures, in situ muscle stimulation to assess contractile function, adenoviral mediated overexpression and/or silencing and metabolic enzyme assays.

Research

Dr. 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 fiber and primary myoblast cultures, in situ muscle stimulation to assess contractile function, adenoviral mediated overexpression and/or silencing and metabolic enzyme assays.

Research

• Biomarkers of cardiac injury
• Evidence-based laboratory medicine

Research

• Biomarkers of cardiac injury
• Evidence-based laboratory medicine

Research

Concerns about the impact of chemical toxicants in the environment on animal and human health are increasing globally. While there is a growing perception that these chemical insults adversely affect the health of animal and human populations, there is still little information regarding the mechanisms underlying their actions. To date, research attention has focused largely on adverse reproductive effects following exposure to environmental contaminants with estrogenic activity and has, for the most part, not examined other endocrine or metabolic outcomes. However, it has been suggested that exposure to environmental contaminants may also have an important role in the etiology of metabolic disorders including type 2 diabetes and obesity.

The overall goal of my research program is to understand the mechanism(s) by which chemical insults can cause metabolic endocrine disruption in animal and human populations. In particular, I am interested in determining how fetal exposure to chemical insults results in adverse postnatal health outcomes in the offspring including type 2 diabetes and obesity. The chemicals that I am interested in studying include: chemicals we may intentionally expose ourselves to through lifestyle choices such as cigarette smoking or the use of over the counter natural health products, man-made chemicals present in the environment and naturally occurring chemicals in our diet (e.g., plant phytoestrogens). To date, the bulk of my research has focused on the long-term health consequences of fetal and neonatal exposure to constituents of cigarette smoke and smoking cessation pharmacotherapies. Specifically, we have been examining the mechanisms by which fetal and neonatal exposure to nicotine, as delivered by maternal smoking or nicotine replacement therapy use can result in pancreatic beta cell damage at birth and the development of type 2 diabetes in the adult offspring. My laboratory is also investigating the consequences of fetal exposure to over the counter natural health products, psychiatric medications and man-made chemicals present in the environment on the development of metabolic disorders in adulthood.

Research

Concerns about the impact of chemical toxicants in the environment on animal and human health are increasing globally. While there is a growing perception that these chemical insults adversely affect the health of animal and human populations, there is still little information regarding the mechanisms underlying their actions. To date, research attention has focused largely on adverse reproductive effects following exposure to environmental contaminants with estrogenic activity and has, for the most part, not examined other endocrine or metabolic outcomes. However, it has been suggested that exposure to environmental contaminants may also have an important role in the etiology of metabolic disorders including type 2 diabetes and obesity.

The overall goal of my research program is to understand the mechanism(s) by which chemical insults can cause metabolic endocrine disruption in animal and human populations. In particular, I am interested in determining how fetal exposure to chemical insults results in adverse postnatal health outcomes in the offspring including type 2 diabetes and obesity. The chemicals that I am interested in studying include: chemicals we may intentionally expose ourselves to through lifestyle choices such as cigarette smoking or the use of over the counter natural health products, man-made chemicals present in the environment and naturally occurring chemicals in our diet (e.g., plant phytoestrogens). To date, the bulk of my research has focused on the long-term health consequences of fetal and neonatal exposure to constituents of cigarette smoke and smoking cessation pharmacotherapies. Specifically, we have been examining the mechanisms by which fetal and neonatal exposure to nicotine, as delivered by maternal smoking or nicotine replacement therapy use can result in pancreatic beta cell damage at birth and the development of type 2 diabetes in the adult offspring. My laboratory is also investigating the consequences of fetal exposure to over the counter natural health products, psychiatric medications and man-made chemicals present in the environment on the development of metabolic disorders in adulthood.

Dr. Marc Jeschke has been caring for burn patients and conducting research in the field of burns for over 25 years. He is a global leader in burn care, research, and education. According to Expertscape, he is the second highest-ranked expert in burns in the world. Dr. Jeschke is currently the Director of the Burn Program at Hamilton Health Sciences Centre, and is a Surgeon Scientist. He is the Vice President of Research for McMaster University, and is a Professor in the Department of Surgery there. Before joining Hamilton Health Sciences, Dr. Jeschke held a faculty position at Sunnybrook in Toronto for 12 years. Prior to that, he was the distinguished Annie Laurie Howard Chair in Burn Surgery at the University of Texas Medical Branch and Shriners Hospital for Children, and worked there as a Staff Surgeon and Coordinator of Research, with a focus on increasing research productivity and obtaining independent grant funds.

Dr. Jeschke has a continuous commitment to scholarly work with over 450 peer-reviewed articles, books, and book chapters on burn care. He has been funded continuously since 2000 and has a significant track record of successes with federal funding agencies and private foundations. He has a total lifetime funding of over $20,000,000 as principal or co-investigator. Dr. Jeschke has an essential role in worldwide multicenter clinical trials and is currently engaged in multiple ongoing multi-centre trials. His work is translational and his research interests include investigating the profound metabolic alterations post-burn injury and novel techniques for wound coverage and skin regeneration.

Dr. Marc Jeschke has been caring for burn patients and conducting research in the field of burns for over 25 years. He is a global leader in burn care, research, and education. According to Expertscape, he is the second highest-ranked expert in burns in the world. Dr. Jeschke is currently the Director of the Burn Program at Hamilton Health Sciences Centre, and is a Surgeon Scientist. He is the Vice President of Research for McMaster University, and is a Professor in the Department of Surgery there. Before joining Hamilton Health Sciences, Dr. Jeschke held a faculty position at Sunnybrook in Toronto for 12 years. Prior to that, he was the distinguished Annie Laurie Howard Chair in Burn Surgery at the University of Texas Medical Branch and Shriners Hospital for Children, and worked there as a Staff Surgeon and Coordinator of Research, with a focus on increasing research productivity and obtaining independent grant funds.

Dr. Jeschke has a continuous commitment to scholarly work with over 450 peer-reviewed articles, books, and book chapters on burn care. He has been funded continuously since 2000 and has a significant track record of successes with federal funding agencies and private foundations. He has a total lifetime funding of over $20,000,000 as principal or co-investigator. Dr. Jeschke has an essential role in worldwide multicenter clinical trials and is currently engaged in multiple ongoing multi-centre trials. His work is translational and his research interests include investigating the profound metabolic alterations post-burn injury and novel techniques for wound coverage and skin regeneration.

RESEARCH

The Kretz Lab is focused on understanding the biochemical and genetic regulation of the blood clotting system. We use traditional tools in protein biochemistry and molecular biology to map protein interactions and define the regulation of proteases in the cardiovascular system. We also employ high throughput screening techniques to understand the impact of genetic variants on blood clotting genes. Our goal is to develop novel tools to treat and diagnose cardiovascular diseases. We collaborate extensively with researchers at TaARI, McMaster University and beyond to achieve our research goals.

RESEARCH

The Kretz Lab is focused on understanding the biochemical and genetic regulation of the blood clotting system. We use traditional tools in protein biochemistry and molecular biology to map protein interactions and define the regulation of proteases in the cardiovascular system. We also employ high throughput screening techniques to understand the impact of genetic variants on blood clotting genes. Our goal is to develop novel tools to treat and diagnose cardiovascular diseases. We collaborate extensively with researchers at TaARI, McMaster University and beyond to achieve our research goals.

Research

Studying the development of peptide immunotherapy for immunological diseases.

Research

Studying the development of peptide immunotherapy for immunological diseases.

Research

• Cell Biology and regulation

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.

Research

• Cell Biology and regulation

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.

Research

Dr. Mukherjee expertise lies in the arena of developing/validating airway biomarkers, mechanisms of airway inflammation and response to biologic therapies. She 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, particularly in asthma, and eosinophilic granulomatosis with polyangiitis (a systemic autoimmune disease with pulmonary complications). Dr. Mukherjee’s research program thus focusses on “Lung autoimmunity and biomarkers”.

Research

Dr. Mukherjee expertise lies in the arena of developing/validating airway biomarkers, mechanisms of airway inflammation and response to biologic therapies. She 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, particularly in asthma, and eosinophilic granulomatosis with polyangiitis (a systemic autoimmune disease with pulmonary complications). Dr. Mukherjee’s research program thus focusses on “Lung autoimmunity and biomarkers”.

Research Areas:

• Clustering of obesity related characteristics and associations with body mass index, waist circumference, and body fatness, Funded by
• Discovery of novel targets and pathways for diabetes remission, Funded by
• Exploring the obesity paradox – The association between body fat distribution and muscle mass on health in the Canadian Longitudinal Study on Aging, Funded by
• Identification of novel causal blood biomarkers to predict micro- and macro-vascular complications of Type 2 diabetes, Funded by
• Large-scale computer-based retinal image analyses combined with genetic and blood biomarker association studies to identify new therapeutic targets for prevention of cardiovascular diseases, Funded by

Research Areas:

• Clustering of obesity related characteristics and associations with body mass index, waist circumference, and body fatness, Funded by
• Discovery of novel targets and pathways for diabetes remission, Funded by
• Exploring the obesity paradox – The association between body fat distribution and muscle mass on health in the Canadian Longitudinal Study on Aging, Funded by
• Identification of novel causal blood biomarkers to predict micro- and macro-vascular complications of Type 2 diabetes, Funded by
• Large-scale computer-based retinal image analyses combined with genetic and blood biomarker association studies to identify new therapeutic targets for prevention of cardiovascular diseases, Funded by

Research

Obesity is one of the most significant health care issues of the 21st century because it increases the risk of cardiovascular disease, type 2 diabetes and hypertension. Obesity related dysfunction can potentially be initiated in utero. Children of obese mothers are at a higher risk of becoming obese and developing these risk factors later in life and this serves to further fuel the obesity epidemic. The environment of the fetus, in the womb, may contribute to the child being predisposed towards developing obesity related disorders as a result of metabolic reprogramming. Mitochondria are one of the central players in cellular metabolisms. They have been classically thought of as oval-shaped organelles responsible for generating ATP and supplying the cells energy demands. They are so much more!

My lab focuses on understanding the role of mitochondrial function/dysfunction in modulating uterine stress as a consequence of maternal obesity. We focus on how physiological stressors affect mitochondrial function and one of their primary by-products, reactive oxygen species. We are interested in understanding the role of mitochondria in contributing to fetal stress in the obese mother. Furthermore, we also focus on how in utero stress can affect mitochondrial function and signaling in dictating fetal and neonatal health of obese mothers. We utilize cell culture and animal models to understand these processes and develop therapeutic strategies to minimize the consequences of maternal obesity 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.

Research

Obesity is one of the most significant health care issues of the 21st century because it increases the risk of cardiovascular disease, type 2 diabetes and hypertension. Obesity related dysfunction can potentially be initiated in utero. Children of obese mothers are at a higher risk of becoming obese and developing these risk factors later in life and this serves to further fuel the obesity epidemic. The environment of the fetus, in the womb, may contribute to the child being predisposed towards developing obesity related disorders as a result of metabolic reprogramming. Mitochondria are one of the central players in cellular metabolisms. They have been classically thought of as oval-shaped organelles responsible for generating ATP and supplying the cells energy demands. They are so much more!

My lab focuses on understanding the role of mitochondrial function/dysfunction in modulating uterine stress as a consequence of maternal obesity. We focus on how physiological stressors affect mitochondrial function and one of their primary by-products, reactive oxygen species. We are interested in understanding the role of mitochondria in contributing to fetal stress in the obese mother. Furthermore, we also focus on how in utero stress can affect mitochondrial function and signaling in dictating fetal and neonatal health of obese mothers. We utilize cell culture and animal models to understand these processes and develop therapeutic strategies to minimize the consequences of maternal obesity 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.

Research Area:

• Chemical Immunomodulatory approaches to combat cancer
• Multivalent metastatic cell targeting oligomers
• Covalent re-engineering of immunological machinery and the cancer cell surface

Research Area:

• Chemical Immunomodulatory approaches to combat cancer
• Multivalent metastatic cell targeting oligomers
• Covalent re-engineering of immunological machinery and the cancer cell surface

Research

Dr. Sheila Singh’s research program is dedicated to applying a developmental neurobiology approach to the study of human brain tumours. As a pediatric neurosurgeon, Dr. Singh is acutely aware of the needs of patients and clinicians dealing with these diseases. Her unique perspective as a surgeon-scientist guides her research questions and areas of focus. The three types of tumours studied by Dr. Singh’s lab are glioblastoma, medulloblastoma and brain metastases. The lab employs a stem cell biology framework to the study of these cancers to identify and target the molecular mechanisms responsible for their development. Their goal is to determine which treatment refractory cells are leading to relapse and recurrence in patients. Ultimately, Dr. Singh’s goal is to be able to take more targeted and effective therapies back to the clinic. To ensure that all of their findings have the potential to be clinically relevant, the Singh lab has cultivated a specialty in developing pre-clinical models and are steadfast in their commitment to working with brain tumour samples direct from human patients.

Research

Dr. Sheila Singh’s research program is dedicated to applying a developmental neurobiology approach to the study of human brain tumours. As a pediatric neurosurgeon, Dr. Singh is acutely aware of the needs of patients and clinicians dealing with these diseases. Her unique perspective as a surgeon-scientist guides her research questions and areas of focus. The three types of tumours studied by Dr. Singh’s lab are glioblastoma, medulloblastoma and brain metastases. The lab employs a stem cell biology framework to the study of these cancers to identify and target the molecular mechanisms responsible for their development. Their goal is to determine which treatment refractory cells are leading to relapse and recurrence in patients. Ultimately, Dr. Singh’s goal is to be able to take more targeted and effective therapies back to the clinic. To ensure that all of their findings have the potential to be clinically relevant, the Singh lab has cultivated a specialty in developing pre-clinical models and are steadfast in their commitment to working with brain tumour samples direct from human patients.

Expertise:  biosensing, point-of-care diagnostics, lab-on-a-chip, DNA detection, health monitoring, nanofabrication, wrinkling, rapid prototyping

Areas of Specialization:

• Biomaterials and Devices
• Imaging, Sensing and Detection
• Smart Systems
• Interdisciplinary Engineering
• Biomedical engineering
• Nano & Micro-systems Engineering

Research Clusters:

• Health & Bio-innovation
• Micro-Nano Systems

Expertise:  biosensing, point-of-care diagnostics, lab-on-a-chip, DNA detection, health monitoring, nanofabrication, wrinkling, rapid prototyping

Areas of Specialization:

• Biomaterials and Devices
• Imaging, Sensing and Detection
• Smart Systems
• Interdisciplinary Engineering
• Biomedical engineering
• Nano & Micro-systems Engineering

Research Clusters:

• Health & Bio-innovation
• Micro-Nano Systems

RESEARCH

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.

RESEARCH

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.

Research

Dr. Weitz researches the molecular mechanisms of coagulation and fibrinolysis with emphasis on the clinical significance of findings.

Mission Statement for TaAri

“To reduce death and disability from thrombotic diseases by conducting research into the pathogenesis, prevention, diagnosis and treatment of thrombosis and vascular disease.”

About TaAri

The Thrombosis & Atherosclerosis Research Insititute (TaARI) is located in the David Braley Research Institute, which they share with the Population Health Research Institute (PHRI) .

The core research programs at TaARI include:

• The Experimental Thrombosis and Atherosclerosis (ETA) Program, led by Jeff Weitz, which conducts fundamental research on the interplay of thrombosis and atherosclerosis with diabetes, cancer and inflammation.
• The Clinical Thromboembolism Program (CTP), led by Sam Schulman, which performs optimal prevention, diagnosis and treatment of patients with thrombotic problems, translating current research into clinical practice.
• The Comparative Medicine Group, led by Shawn Petrik, which supports the research of an interdisciplinary group of faculty veterinarians, physicians and basic scientists who study animal models of human disease. The research is dedicated to the enhancement of human and animal health via research, training and services.
• The Neonatal Trials Group, led by Robin Roberts, which conducts clinical trials to assess the efficacy and safety of common, but insufficiently evaluated, neonatal therapies in premature infants. The research group is co-directed by Barbara Schmidt and Haresh Kirpalani who are now at the University of Pennsylvania. Robin Roberts also provides biostatistical support to all the programs at TaARI.

Research

Dr. Weitz researches the molecular mechanisms of coagulation and fibrinolysis with emphasis on the clinical significance of findings.

Mission Statement for TaAri

“To reduce death and disability from thrombotic diseases by conducting research into the pathogenesis, prevention, diagnosis and treatment of thrombosis and vascular disease.”

About TaAri

The Thrombosis & Atherosclerosis Research Insititute (TaARI) is located in the David Braley Research Institute, which they share with the Population Health Research Institute (PHRI) .

The core research programs at TaARI include:

• The Experimental Thrombosis and Atherosclerosis (ETA) Program, led by Jeff Weitz, which conducts fundamental research on the interplay of thrombosis and atherosclerosis with diabetes, cancer and inflammation.
• The Clinical Thromboembolism Program (CTP), led by Sam Schulman, which performs optimal prevention, diagnosis and treatment of patients with thrombotic problems, translating current research into clinical practice.
• The Comparative Medicine Group, led by Shawn Petrik, which supports the research of an interdisciplinary group of faculty veterinarians, physicians and basic scientists who study animal models of human disease. The research is dedicated to the enhancement of human and animal health via research, training and services.
• The Neonatal Trials Group, led by Robin Roberts, which conducts clinical trials to assess the efficacy and safety of common, but insufficiently evaluated, neonatal therapies in premature infants. The research group is co-directed by Barbara Schmidt and Haresh Kirpalani who are now at the University of Pennsylvania. Robin Roberts also provides biostatistical support to all the programs at TaARI.

Research

In the Hope Lab, our research program is focused on dissecting the molecular regulation of normal and malignant hematopoietic stem cell (HSC) self-renewal and hopes to identify the underlying processes that ultimately lead to leukemic transformation and progression.

Research

In the Hope Lab, our research program is focused on dissecting the molecular regulation of normal and malignant hematopoietic stem cell (HSC) self-renewal and hopes to identify the underlying processes that ultimately lead to leukemic transformation and progression.

Research

Our primary research objective is to understand the pathological mechanisms of psychiatric disorders including schizophrenia and autism spectrum disorders. Neuropsychiatric diseases including autism, schizophrenia and bipolar disorder are a major problem in our society as patients have few successful treatment options. One of the reasons is because scientists do not understand the pathogenic mechanisms of these diverse diseases, which makes discovering new drugs for treatment very difficult. Interestingly, neuropsychiatric illnesses tend to run in families, which means there is a genetic basis for these diseases. However, only recently have we started to discover the genes that are responsible for increasing risk of disease. Furthermore, there is a lack of model organisms (e.g., mouse models) that can faithfully recapitulate the genetic diversity and heterogeneity of these brain disorders.

Research

Our primary research objective is to understand the pathological mechanisms of psychiatric disorders including schizophrenia and autism spectrum disorders. Neuropsychiatric diseases including autism, schizophrenia and bipolar disorder are a major problem in our society as patients have few successful treatment options. One of the reasons is because scientists do not understand the pathogenic mechanisms of these diverse diseases, which makes discovering new drugs for treatment very difficult. Interestingly, neuropsychiatric illnesses tend to run in families, which means there is a genetic basis for these diseases. However, only recently have we started to discover the genes that are responsible for increasing risk of disease. Furthermore, there is a lack of model organisms (e.g., mouse models) that can faithfully recapitulate the genetic diversity and heterogeneity of these brain disorders.