Our Research Members

Dr. Connelly is a clinician scientist and staff physician at St Michael’s Hospital where his clinical responsibilities involve echocardiography and cardiac MRI. His basic science laboratory is involved in exploring mechanisms of diabetic complications, principally diastolic heart failure and developing novel therapeutic strategies to treat this. Dr. Connelly also collaborates closely with the Sunnybrook Health Sciences Centre in elucidating the role of real time cardiac metabolism in the pathogenesis of post MI remodeling, and developing novel MR techniques to enable non-invasive tissue characterization.

The research interests of the laboratory are in the study of patients at risk for Type 2 Diabetes or at risk for the complications of diabetes and identifying serum biomarkers that will predict patient outcomes. The most recent focus has been on the adipokine adiponectin and on the enzyme paraoxonase-1 (PON1). Adiponectin is an insulin-sensitizing protein produced by adipocytes.PON1 is an anti-inflammatory component of high density lipoproteins. We have studied these factors in four patient groups:
1) The Sandy Lake Oji-Cree
2) Women at risk for post-gestational diabetes
3) Patients with renal failure on dialysis; and
4) Renal transplant recipients

Type-1 diabetes (T1D) is an autoimmune disease characterized by loss of self-tolerance, T cell-mediated immune attack of pancreatic β-islets and β-cell dysfunction. Allogeneic β-islet transplantation can restore β-islet cell function but despite the use of immunosuppressive drugs, the risk of allo- and autoimmune-mediated b-cell loss remains high. A true ‘cure’ for T1D requires approaches that restore β-islet function and also prevent immune-mediated pathology without immunosuppressive drugs. Our lab focuses on harnessing lymphocyte populations that have immunoregulatory or tissue repair properties in cell-based therapies for transplantation and autoimmunity. Ongoing studies are focused on delineating cross-talk between immune cells and β-islet cells, and assessing whether adoptive transfer of populations of lymphocytes can enhance β-islet cell transplantation approaches by regulating aberrant immune responses or supporting β-islet cells directly.

Developing optical technologies to assess tissue viability in the diabetic lower extremity. The aim is to develop novel devices in the prevention, diagnosis and management of Diabetic Foot Ulcers (DFU’s). The research laboratory is a combination of physics, engineering and clinical translation with the aim to have a direct impact on the lives of patients.

Research in the Cummins lab relates to the study of nuclear hormone receptors that are important in the control of glucose and lipid metabolism. Our lab is interested in all areas of nuclear receptor biology including the identification of new ligands; the study of signaling pathways upstream and downstream of receptor activation; the characterization of novel co-regulatory proteins; and the influence of nuclear receptor modulation on whole animal physiology. Our studies primarily investigate the importance of the glucocorticoid receptor (GR), the liver X receptor  (LXRα and LXRβ) and the peroxisome proliferator activated receptor (PPARα, PPARδ and PPARγ) signaling pathways in the context of diabetes and dyslipidemia.

The goal of Dr. Cybulsky’s research program is to elucidate novel cellular and molecular mechanisms regulating intimal macrophage burden at early stages of atherosclerosis. The vision is to use this information to develop new therapies to inhibit the progression of early atherosclerotic lesions to advanced plaques. Individuals with known risk factors for atherosclerosis would benefit from such therapies because complications arising from advanced plaques cause myocardial infarction and stroke, and therapies that inhibit disease progression would alleviate the morbidity and mortality associated with atherosclerosis. Our research program to reduce intimal macrophages in early atherosclerotic lesions and inhibit lesion progression focuses on several aspects of myeloid cell biology including macrophage exit from atherosclerotic lesions, inhibition of monocyte recruitment, macrophage proliferation and survival in early lesions and understanding how systemic risk factors influence macrophage gene expression triggered by pro-inflammatory stimuli. Previous research has focused on hypercholesterolemia, a key risk factor for atherosclerosis; however, future studies will also include hyperglycemia and advanced glycation endproducts, which are found in patients with diabetes. The burden of diabetes, particularly adult onset or type II diabetes, is increasing, as is its contribution to atherosclerosis-related conditions.

The focus of Dr. Danska’s research is defining mechanisms of immune mediated diseases and application of this knowledge to improve their diagnosis, prevention and treatment.  Her lab works on the genetic and environmental causes of autoimmune disease, particularly Type 1 diabetes (T1D) in animal models and prospective human cohort studies. Her group found that manipulation of the intestinal microbial community (microbiome) strongly influences levels of sex hormone levels, host metabolites and can protect mice with high inherited risk from T1D.  She has led international projects that identified diabetes risk genes and determined how these variants control immune pathogenesis.  Her current work is focused on identification of environmental factors responsible for the rise in rates of autoimmune and inflammatory diseases, and how these factors are modified by the intestinal microbiome. She has a long-standing interest in sex as a determinant of autoimmune disease risk and pathogenesis.

I am interested in obesity and insulin resistance. More specifically I aim to assess the role of the central nervous system in mediating various metabolic processes in humans in responses to drugs and peptides. Another avenue of research I will explore is investigating the etiology of obesity, its metabolic complications and response to treatment. I aim to utilize a combination of integrative in vivo physiology, genetic and pharmacological approaches to answer these research questions with the ultimate aim of potentially developing novel therapies for metabolic disorders.

I pursue population-based health services research focusing on patients with diabetes who undergo lower limb amputation. I am interested in better characterizing the epidemiology, outcomes, health-resource use and costs of lower limb amputation in diabetic patients as well as limb preservation therapies. The purpose of this work is to inform population-level interventions to reduce diabetes-related foot complications.

My lab is interested in skeletal muscle biology and how phosphoinositides regulate the transport of vesicles within the muscle and how they govern exocytosis. This has direct relevance to diabetes, as these pathways are critical for regulating insulin dependent GLUT4 trafficking and, as such, muscle dependent regulation of insulin sensitivity. PIPs and their regulatory enzymes also influence secretion of myokines. Myokines are critical for muscle crosstalk with other organs, including the brain, liver, and adipose tissue. Muscle dependent organ cross talk is an emerging area of regulation of whole body metabolism, and can influence development of diabetes and modulate its sequelae. Lastly, we are very interested in therapy development. We hypothesize that modulation of the PIP pathway will provide a novel, muscle specific treatment strategy for diabetes. We are actively working on developing such a therapy, targeting specifically one of the PIP enzymes.

Research in the Drucker lab is focused on understanding the biology of gut hormones, with a major focus on GIP and the glucagon-like peptides. The lab studies how glucagon, GIP, GLP-1, and GLP-2 regulate energy homeostasis, metabolic control, and cardiovascular function via effects on the gastrointestinal tract, pancreas, cardiovascular system and central nervous system. Specific projects elucidate novel mechanisms of glucagon, GIP, GLP-1 and GLP-2 action through studies of their respective receptors in peripheral tissues. Research staff utilize a combination of techniques that involve studies of signal transduction, generation of transgenic or knockout mice, and studies of rodent models of peptide hormone action with a focus on diabetes, obesity, endocrine systems, and intestinal disease.

Diabetes Mellitus and Cardiovascular Disease: The main focus is the evaluation of diabetic patients with coronary artery disease, acute coronary syndromes and heart failure. We have examined the role of advanced multi-modal imaging in developing novel compounds to treat atherosclerosis in diabetic patients. I have conducted large-scale clinical trials such as the FREEDOM Trial which evaluated the optimal strategy required for the management of coronary artery disease. Our goal for the future is to develop a collaborative coordinating center to address the important clinical questions revolving around diabetes and heart disease.

Main research interest is in the area of diabetes in pregnancy.
We are currently conducting a multi-centre randomized controlled trial of metformin use in women with type 2 diabetes in pregnancy (MiTy trial).
I am also involved in studies looking at the placental transfer of diabetes drugs in pregnancy, the transfer of diabetes drugs into breast milk, and administrative databases looking at women with diabetes in pregnancy in Ontario.

The Feng lab is interested in understanding the mechanisms underlying synapse development and synaptic transmission using various in vitro and in vivo animal models. The major lines of research in the Feng Lab include 1) identifying the roles of ion channels in neurons and pancreatic cells under physiological and pathophysiological conditions, 2) determining the regulatory mechanisms of the ion channels, and 3) understanding neuronal control of hormone secretion in control and diabetic rodent models. The technical expertise in the Feng lab includes patch-clamp recordings, dynamic ratiometric imaging, confocal imaging, molecular biology and biochemistry.

Our lab studies the role of microRNAs in controlling vascular inflammation. We have a particular interest in determining the role of circulating microRNAs in disease pathogenesis, and exploring their use as biomarkers. We are studying mouse models of diabetic cardiomyopathy to define disease mechanisms that involve microRNAs and we are identifying circulating microRNA biomarkers in human patient cohorts with diabetes, diabetic cardiomyopathy and/or end-stage renal disease.

The general theme of the Floras Clinical Cardiovascular Physiology Laboratory has been the elucidation of mechanisms responsible for initiation and progression of cardiovascular and related diseases in humans, through interdisciplinary patient oriented research.

Neural and intrinsic cardiovascular regulation is studied using: microneurographic recordings of sympathetic nerve discharge directed at resistance vessels, tracer kinetic methods to estimate total body norepinephrine spillover, spectral analysis of heart rate variability and baroreflex sensitivity for heart rate, plethysmographic methods for assessing blood flow, and ultrasonic methods for quantifying endothelium dependent and independent vasodilatation.

These methods have been applied to research questions concerning normal health and aging, and to conditions such as heart failure, sleep apnea, hypertension, renal failure, pulmonary hypertension, diabetes (in collaboration with Drs. Zinman, Millar and Meneilly), menopause and cirrhosis.

Michael Fralick’s main research interest is in understanding the safety and effectiveness of sodium glucose co-transporter 2 (SGLT2) inhibitors by applying pharmacoepidemiology methods and machine learning. He primarily uses data collected from routine care (e.g., ICES, insurance claims data) and his main areas of methodologic expertise are in propensity score matching and supervised machine learning (e.g., gradient boosted trees). 

Increasing evidence now points to the deposition and cytotoxicity of islet amyloid polypeptide aggregates as major contributors to loss of beta cell mass and ultimately the progression to type 2 diabetes. Amyloid aggregation may also contribute to graft failure following islet transplantation in type 1 diabetes patients. Therefore, our research involves devising new ways to inhibit islet amyloid aggregation and protect beta cells, thereby slowing or preventing onset of type 2 diabetes and improving islet graft survival.

To study the molecular relationship between vitamin D endocrine system and diabetes.

Research in the Gaisano lab is focused on molecular mechanisms regulating exocytosis, employing islet cells as models. We were one of the firsts to demonstrate that SNARE proteins originally found to mediate neurotransmitter release are conserved in non-neuronal cells, including the pancreatic islet to regulate secretion. We contributed to the original work showing SNARE protein regulation of insulin granule exocytosis, and subsequently contributed much of the work showing how SNARE proteins physically and functionally interact with beta-cell ion channels (Kv, KATP, Ca2+) to regulate the intricate sequence of ion fluxes, membrane potential and exocytotic fusion events leading to secretion.  Current efforts are a continuation of the above (1 and 2) plus two new directions (3 and 4).  1) SNAREs interactions with Kv and Ca2+ channels forming ‘excitosomes’ and how these excitosomes are involved in the insulin granule exocytotic machinery for predocked (first phase insulin secretion) and newcomer granules (second phase insulin secretion); and how these insights could reveal rescue strategies for T2D insulin secretory deficiency. 2) Islet alpha cell secretory mechanisms and crosstalk with beta- and delta-cells in health and their dysregulation in T1D.  For these 2 directions, we are using human T1D and T2D pancreas as well as normal human pancreas.  3) Using the transparent anterior chamber of the mouse eye, we are observing the behaviour of implanted human islets, a capability that we directing at assessing human T1D and T2D islet biology over a long duration, their responses to novel treatment strategies, and also islet regenerative medicine.  4) Role of the intestinal microbiome in its contribution to the pathogenesis of the metabolic syndrome, and identifying new treatment strategies. The Gaisano lab has in place a full spectrum of state-of-the-art technologies to assess these four funded directions.