Our Research Members

We study systemic dissemination mechanisms of bloodborne bacterial pathogens, with a focus on the Lyme disease pathogen, Borrelia burgdorferi. Lyme disease is the most common vector-borne infection in the industrialized world, and its incidence is increasing rapidly, in parallel with rising rates of obesity and diabetes. Systemic dissemination of pathogens causes most of the mortality due to bacterial infection, but remains poorly understood. One critical step in dissemination is microbe adhesion to blood vessel surfaces in the face of fluid shear force. Vascular adhesion enables pathogens to decelerate and transmigrate through vessels to reach extravascular tissues in joints, heart and brain where secondary infection is established. B. burgdorferi adheres more readily to sites of turbulent, altered blood flow (Moriarty et al., 2008). This observation, together with the epidemiological profile of Lyme disease, prompted us to examine the effect of blood flow-altering conditions such as diet-induced obesity on B. burgdorferi dissemination in mice. We have found that diet-induced obesity significantly enhances host susceptibility to disseminated Borrelia infection, and are currently investigating the mechanisms underlying this increased susceptibility, as well as the role of diabetes in host susceptibility to Lyme disease.

The overarching goal of my research is to optimize psychiatric medication treatment by using genetic information and to implement genetic testing in clinical practice in order to implement precision medicine in psychiatry. More specifically, many psychiatric medications, and in particular most antipsychotic medications, commonly cause substantial weight gain which frequently leads to obesity and metabolic syndrome, including T2DM. These metabolic disturbances are one reason why the life expectancy of patients with mental illness is significantly reduced.

Our research has revealed significant associations between antipsychotic-induced weight gain (AIWG) and genetic polymorphisms involved in the appetite and satiety regulating hypothalamic pathways.

We are currently developing an algorithm that will incorporate these genes along with clinical and demographic risk factors which will result in a genetic risk model for clinical application. Such algorithm will help to identify patients at risk for AIWG in order to optimize and personalize medication accordingly.

Somatic cell reprogramming to induced pluripotent stem cells requires the expression of 2-4 key transcription factors. We have demonstrated that the piggyBac transposon-based transgene delivery system combined with tetracycline inducible gene expression can be used to reprogram cells with a comparably high efficiency to viral transduction, both from mouse and human somatic cells. Unique properties of our transposon-based system form the foundation for exploring the plasticity of the ß-cell. Using a transgenic reprogrammable mouse line, we are exploring the possibility expanding, differentiating and trans-differentiating cells of the pancreatic lineage in a whole organism context and ex vivo. T his research aims to take a giant leap forward in the understanding of the cellular plasticity of ß-cells and the development of novel tools for bringing efficient cell-based therapies to the future of medicine.

My research lab is primarily interested in the area of genetics of lipid disorders and cardio-metabolic disorders with special emphasis on high density lipoprotein (HDL) metabolism. We use transgenic/knock out mice as models and our tools include in vivo experiments, ex vivo and in vitro assays at tissue, cellular, and molecular levels. We are particularly interested in using in vivo mouse models to examine the impact of specific genetic-based dyslipidemic states on atherogenesis, diabetogenesis and more recently, obesity and brown fat development. Detailed analyses of these animal models using cellular, molecular and genetic markers will also be carried out to elucidate the underlying mechanism of such disease processes and their interactions. Such genetic models are also used to study the effects of dietary and drug interventions.

– Generation of pancreatic beta cells from human pluripotent stem cells
– Cell therapy for type I diabetes
– Modeling lineage commitment and human development in vitro
– Using human pluripotent stem cell-derived pancreatic cells as a platform for drug screening

We are investigating how diabetes affects vessel formation (angiogenesis and arterio-venous specification) and its implications in tissue engineering for regenerative medicine. Moreover, we are investigating the direct effects of diabetes and diabetes-related drugs on crdiovascular health including human stem cell-derived cardiomyocyte organoid models.

• Exercise and lifestyle interventions for the prevention and management of diabetes
• Patient education to enhance self management and health behaviours

I care for children and adolescents with type 1 and type 2 diabetes mellitus. I have been involved in diabetes related clinical research as a Principal Investigator in the NIH multicentered trial entitled Treatment Options for Type 2 Diabetes in adolescents and Youth (TODAY), which was designed to identify best ways to treat type 2 diabetes in youth. I have also been Principal Investigator the Clinical Coordinating Center for the NIH/NIDDK funded Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) trial.

Currently, my diabetes related research includes membership in the Hvidoere Study Group of Childhood Diabetes, using technology to enhance diabetes self-management, and quality improvement within clinical practice, including working to improve transitions from pediatric to adult care. 

Type 2 diabetes is one of the most serious public health issues in Canada and on a global scale. There are striking differences in prevalence among ethnic groups. The prevalence of type 2 diabetes among Aboriginal people is higher than in the general population, and elevated risk has also been described for other groups, such as Hispanics. One of the major goals of Dr. Parra’s research is to identify type 2 diabetes genetic risk factors in Hispanic populations, using different approaches, such as candidate gene studies, admixture mapping and genome-wide association.

I have worked as a Nurse Practitioner in Cardiac Surgery since 1998, and in my role have cared for many individuals with diabetes (T2DM). Many patients who have sternal wound infections have diabetes, and many individuals have poor blood sugar control following cardiac surgery. I am interested in the prevention of complications in individuals with diabetes, with a specific interest is in sex and gender and the prevention of cardiovascular disease. I have been a co-investigator with Dr. Stewart Harris investigating diabetes in several Indigenous (First Nation, Inuit and Métis) communities in Canada, am a co-investigator and member of the Training and Mentoring and Knowledge Translation Goal  Groups with Diabetes Action Canada (DAC), and have received funding from the Canadian Institutes of Health Research (in collaboration with Clinical Trials Ontario) to build capacity for Patient-Oriented Research in Canada.

Long-term complications of diabetes, including eye and kidney disease cluster in families suggesting that genetic factors may be involved. Using DNA from large numbers of people with diabetes who have their complications measured, we are using high throughput methods to measure all of the common genetic variation in the human genome to identify which ones are associated with specific complications. In addition, we are identifying genetic loci that are associated with the major risk factors for diabetes complications – glycemia, blood pressure, body composition and lipids.

Using longitudinal cohort methods as well as clinical trials, my research focuses on 1) Early biomarkers of diabetes complications (with a focus on neuropathy and kidney disease) and 2) Interventions for prevention of complications, including automated insulin delivery (‘artificial pancreas’) technologies and disease-modifying adjunctive-to-insulin pharmacotherapies in type 1 diabetes. I am a principal investigator in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and I co-lead an Innovations in Type 1 Diabetes group within Diabetes Action Canada, a national patient-oriented research strategy.

We are interested in the role of innate immunity, specifically Nod like receptors, as well as the microbiota in diabetes pathogenesis.

The objective of our research program is to study the role of differential colonization of the intestine by commensal bacteria on the development of anti-pancreatic autoimmunity in humans and murine models of the disease with the objective to understand how environmental changes can affect the expression of diabetogenic genotypes.

Our laboratory is interested in the identification and characterization of circulating factors influencing beta cell function during the pathogenesis of diabetes. Utilizing a combination of animal models, human patient samples, primary tissues, clonal cell lines, and molecular biology approaches, we aim to interrogate how inter-organ communication via proteins and metabolites is altered early in the development of both type 1 and type 2 diabetes, contributing to the overt manifestation of disease. Ultimately, we hope to identify novel biomarkers and therapeutic targets that can be harnessed to prevent or delay diabetes development.

Research in my laboratory focuses on the immunology, pathogenesis and therapy of type 1 diabetes. We are investigating drugs that can induce the regeneration of pancreatic beta cells, or prevent beta-cell death.  This includes studies of GABA, GLP-1, Klotho, TGF-beta inhibitors, and other molecules or drugs relevant to diabetes therapy. In many cases, human pancreatic islets are transplanted into immunodeficient cells for in vivo studies. This work requires the application of a wide variety of immunological, biochemical, cellular and molecular biological techniques, in relevant disease models.

Dr. Mohammad Qadura has been actively involved in diabetes research, particularly focused on identifying novel biomarkers for diabetic complications. His preliminary work has shown promise in finding circulating biomarkers that are differentially expressed in diabetic foot ulcers compared to controls. This could aid in early screening and prognostication of diabetic foot ulcers, which is key to preventing limb amputations. Dr. Qadura aims to file a patent for his research findings, with the hope of commercializing his research.

Previously, he has looked at studies investigating other biomarkers in patients with diabetes. A paper describes his research evaluating fatty acid binding protein 4 (FABP4) levels in diabetic patients with and without peripheral arterial disease (PAD). The study found higher FABP4 levels were associated with presence and severity of PAD in diabetes independent of confounders. It also showed good diagnostic potential for detecting PAD. This adds to evidence that biomarkers linked to inflammation, atherosclerosis and metabolic dysfunction may have clinical utility in assessing vascular complications in diabetes.

Overall, Dr. Qadura’s research aims to identify novel biomarkers that can improve management of diabetes and its micro- and macro-vascular sequalae like diabetic foot ulcers, retinopathy, nephropathy and PAD. His goal is to find clinically useful biomarkers that can enable early detection, prognostication and personalized therapy for diabetic patients. This could significantly improve outcomes and quality of life for the millions suffering from diabetes worldwide.

Deficiencies in maternal diet or exposure to environmental toxins during pregnancy can affect developmental trajectories and program postnatal disease propensity in the progeny, including metabolic disorders and diabetes. The mechanisms that underlie the environmental modulation of developmental and stem cell biology remain largely unknown. We are investigating the impact of a variety of environmental stressors during gestation on epigenetic states in fetal cells and physiological outcomes into adulthood and across generations. For example, we have implemented mouse models wherein nutritional deficits during pregnancy induce glucose intolerance and insulin resistance in the progeny.  We are dissecting the underlying molecular and cellular mechanisms using cutting-edge epigenomics approaches. We anticipate that this knowledge may reveal avenues to both prevent developmental programming of diabetes from occurring in the first place as well as to epigenetically reverse it after the disease manifests.

My research program focuses on the pathophysiology and treatment of type 2 diabetes (T2DM), with a particular interest in the potential reversibility of pancreatic beta-cell dysfunction early in the course of diabetes. In this context, our research group is conducting a series of innovative clinical trials evaluating novel therapeutic strategies for the preservation of beta-cell function in early T2DM, including the CIHR-funded RESET IT Trial and PREVAIL Trial. In addition, our research program has highlighted the concept that a women’s gluco-regulatory response to the metabolic challenge posed by pregnancy can provide unique insight into her future risk of T2DM and cardiovascular disease later in life. This concept is being studied with CIHR-funded prospective observational cohorts in Toronto and China.

Interaction between pancreatic islets and vascular endothelial cells is necessary for the maintenance of beta-cell mass and function. Aside from acting as a conduit for molecular oxygen, vascular endothelial cells in vivo secrete the majority of islet extracellular matrix (ECM). This ECM likely provides a permissive signal for beta-cell proliferation, contributing to the coordinated hyperplasia of these tissues during the early stages of Type 2 diabetes. This ECM also provides a reservoir for heparin binding growth factors that further modulate this hyperplasia, including fibroblast growth factor (FGF) and vascular endothelial growth factor-A (VEGF-A). We hypothesize that communication between beta-cells and vascular endothelial cells directs the proliferation and function of both tissues.