Our Research Members

Lori MacCallum
MacCallum, Lori
BScPhm, PharmD, CDE
U Of T Appointments

Program Director, Knowledge Translation and Optimizing Care Models, Banting & Best Diabetes Centre
Assistant Professor, Leslie Dan Faculty of Pharmacy

Contact Information
Banting & Best Diabetes Centre
200 Elizabeth St., Eaton Building, Room 12E252
Toronto, ON M5G 2C4
Phone: 416-340-4800 x2784
Fax: 416-978-4108
lori.maccallum@uhnresearch.ca
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Diabetes Related Research Activities:

Knowledge Translation Projects particularly in improving the care of patients with diabetes, innovative pharmacy interventions, using multimedia for patient education, and educating patients on risks and benefits of medications.

Radhakrishnan Mahadevan
Mahadevan, Radhakrishnan
Ph.D.
U Of T Appointments

Associate Professor, Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering

Contact Information
Wallberg Building 326
200 College Street
Toronto, ON M5S 3E5
Phone: 416-946-0996
Fax: 416-978-8605
krishna.mahadevan@utoronto.ca
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Diabetes Related Research Activities:

We aim to use a systems biology approach for understanding the mechanisms behind and diabetes and the role of potential therapeutic strategies. Our focus is on describing glucose, insulin, glucagon, TAG, levels at the whole body level using an multi-scale metabolic model. We hope to integrate phenomena across spatial scales from cellular to tissue to organ as well as temporal scales from s-min to hours. Using these models, we aim to understand the sensitivity of the different factors affecting this complex disease.

Farid H. Mahmud
Mahmud, Farid H.
MD, FRCPC
U Of T Appointments

Assistant Professor, Faculty of Medicine

Other Appointments

Division of Pediatric Endocrinology, The Hospital for Sick Children

Contact Information
The Hospital for Sick Children
555 University Avenue
Toronto, ON M5G 1X8
Phone: 416-813-6218
Fax: 416-813-6304
farid.mahmud@sickkids.ca
Diabetes Related Research Activities:

As a pediatric endocrinologist who cares for children with diabetes, obesity and other chronic medical conditions on a daily basis, I am concerned about the prospects for their future health. This has driven me to seek answers to some of the meaningful questions that are going to benefit their health and this has prompted me to pursue a clinical research program. My research interests include the study of conditions associated with type 1 diabetes, such as celiac disease and the evaluation of early atherosclerotic risk factors in young patients with endocrine conditions who are at high risk of cardiovascular disease including both type 1 and type 2 diabetes, insulin resistance and obesity. I have conducted clinical studies to identify patients at risk and study the impact of this process on the health of these children.

These studies are also evaluating interrelated risk factors for atherosclerosis in these high risk populations and the effectiveness of lifestyle, diet and drug therapy treatment strategies. Specifically we evaluated dietary intake in patients with type 1 diabetes as well as standardized activity assessments which showed high rates of dietary fat intake and inactivity, which worsened during adolescence. As part of my research, I adapted an innovative method to study endothelial function as a marker of early atherosclerosis which we able to evaluate as a reversible indicator of disease with the potential to assess the effectiveness of different treatment strategies on reducing early atherosclerotic changes.

Longer term, the findings of this research will be used to develop guidelines for clinical practice, prevention and treatment strategies. It is hoped that the effective translation of this research into clinical practice will help to manage cardiovascular disease risk in children with the ultimate goal of cardiovascular disease prevention.

Muhammad Mamdani
Mamdani, Muhammad
PharmD, MA, MPH
U Of T Appointments

Professor, Institute of Health Policy, Management, and Evaluation of the Faculty of Medicine and the Leslie Dan Faculty of Pharmacy

Other Appointments

Director, Applied Health Research Centre, Li Ka Shing Knowledge Institute,St. Michael’s Hospital

Contact Information
St. Michael's Hospital
30 Bond Street
Toronto, ON M5B 1W8
Phone: 416-864-3037
Fax: 416-864-3014
mamdanim@smh.ca
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Diabetes Related Research Activities:

The Applied Health Research Centre (AHRC) is a comprehensive, not-for-profit, academic clinical research centre that houses leading clinical research methodologists and statisticians as well as operations experts including contracts and finance experts, study management coordinators, and research informatics specialists. Further, the AHRC also houses industry-standard and highly secure data management infrastructure. The AHRC has extensive experience designing and implementing phase 2b-4 clinical trials as well as nonrandomized studies such as patient registries and retrospective database studies. The infrastructure and support services are available to all academic clinical researchers and is well suited for diabetes-related clinical research.

Christopher McCulloch
McCulloch, Christopher
PhD, DDS, Certificate in Periodontics
U Of T Appointments
  • Professor, University of Toronto, Faculty of Dentistry
  • Cross-appointed to Department of Laboratory Medicine and Pathobiology, Faculty of Medicine
Other Appointments
  • Canada Research Chair in Matrix Dynamics
  • Director, Matrix Dynamics Group, Faculty of Dentistry
  • Full Member, School of Graduate Studies
  • Director, CIHR STIHR, “Cell Signalling in Mucosal Health and Disease”
  • Consultant, Royal College of Dental Surgeons of Ontario (RCDSO), Toronto, ON
Contact Information
FitzGerald Building, Room 244
150 College Street
Toronto, ON M5S 3E2
Phone: 416-978-1258
Fax: 416-978-5956
Christopher.Mcculloch@utoronto.ca
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Diabetes Related Research Activities:

My laboratory is focused on the signals arising from the extracellular matrix that regulate the metabolic activities of fibroblasts. In the context of diabetes, I am interested in the notion that diabetes-induced glycation of collagen may impact the function and differentiation of fibroblasts in the cardiac interstitium. Accordingly, I cardiac fibroblasts may convert to myofibroblasts, cells that contribute to the fibrosis that is observed in diabetic cardiomyopathy.

Tracy McGaha
McGaha, Tracy
PhD, MS, BS
U Of T Appointments

Associate Professor, Department of Immunology

Other Appointments

Senior Scientist, Princess Margaret Cancer Centre, Tumor Immunotherapy Program

Contact Information
Princess Margaret Cancer Centre
610 University Ave., Room 8-410
Toronto, ON M5G 2M9
Phone: 416-634-7252
tmcgaha@uhnresearch.ca
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Diabetes Related Research Activities:

We are interested in the endoplasmic reticulum stress/unfolded protein response (UPR) and integrated stress response (ISR) signals as drivers of macrophage (MF) phenotype and tissue destruction in autoimmune diabetes (T1D).

MF infiltration in the islets is a well-established mechanistic driver of insulitis and b cell death in T1D. Functionally, infiltrating MF in pancreatic lesions exhibit an inflammatory phenotype with NADPH-driven superoxide and ROS production and TNF-a and IL-1b secretion (in a STAT1-dependent mechanism). Via production of these effector molecules, MF act in a synergistic fashion with infiltrating dendritic cells and T cells to drive islet cell dysfunction and death. Conversely, modulating MF phenotype has a dominant impact on the course of disease in experimental models of spontaneous and induced T1D, reducing the onset and severity of insulitis. Given this, manipulation of MF function becomes an attractive therapeutic target in T1D to control autoimmune pathology and as a tool to promote transplant tolerance.

Cellular stress signals play a key role in myeloid inflammatory potential. UPR stress can drive JNK and STAT1 activation, promote TNFa secretion, and inflammasome maturation/IL-1b production in MF and DC. Likewise the ISR plays a dominant role in controlling MF phenotype and inflammatory potential. For example, our lab demonstrated the ISR kinase GCN2 regulates IL-6 and IL-12 production promoting endotoxemic mortality. However, stress signals can also suppress inflammation as reactive oxygen species driven ER stress promotes myeloid-dependent immune suppression in tumors. Further, we have found GCN2 suppresses inflammatory T cell proliferation and systemic autoimmunity. Importantly modification of stress signaling by pharmacologic approaches has a potent impact on outcomes in inflammation, transplantation, autoimmunity and cancer. These striking findings show stress signaling is a cell and context-dependent modifier of immune function providing novel druggable targets; however, it is paramount to clearly delineate the role (either pro- or anti-inflammatory) of stress signaling modules in the pathologic process.

In our research project we are examining the role of metabolism and stress signaling in inflammatory pathology in T1D using mouse models of disease. Moreover we are examining the follow-on prediction that manipulation of MF phenotype via antagonists or agonists of UPR stress and/or the ISR will modulate the phenotype of MF; thereby reducing autoimmune pathophysiology and/or promoting islet transplant acceptance.

Roger S. McIntyre
McIntyre, Roger S.
U Of T Appointments

Associate Professor of Psychiatry and Pharmacology

Other Appointments

Head, Mood Disorders Psychopharmacology Unit (MDPU), University Health Network

Contact Information
Toronto Western Hospital, MP9-325
399 Bathurst Street
Toronto, ON M5T 2S9
Phone: 416-603-5279
Fax: 416-603-5368
roger.mcintyre@uhn.on.ca
Diabetes Related Research Activities:

Individuals with mood disorders are differentially affected by abnormalities in glucose handling, hyperglycemia, and diabetes mellitus. Evidence indicates that both mood disorders and diabetes are highly associated with neurocognitive impairment as well as changes in brain volume and structure. Points of pathophysiological commonality have been implicated between mood disorders and diabetes and include alterations in metabolic effector systems, immunoinflammatory dysregulation, oxidative stress, and incretin systems. We have coined the moniker “Metabolic Syndrome Type II” to characterize these points of commonality. The Mood Disorder Psychopharmacology Unit (MDPU) is engaged in a plethora of both descriptive and interventional studies that aim to identify the effect of abnormal glucose homeostasis, insulin resistance, and incretin dysregulation on brain structure and function. The MDPU welcomes multidiscipline centre of excellence and research characterizing the psychiatry and endocrinology interface.

Alan Moody
Moody, Alan
MBBS, FRCP, FRCR
U Of T Appointments

Professor, Department of Medical Imaging
Associate Professor, Department of Medical Biophysics
Full member Institute of Medical Sciences
Chair, Department of Medical Imaging

Other Appointments

Senior Scientist, Sunnybrook Research Institute
Staff Radiologist, Sunnybrook Health Sciences Centre

Contact Information
Sunnybrook Health Sciences Centre Room M7 615
2075 Bayview Ave.
Toronto, ON M4N 3M5
Phone: 416-480-6100 x89432
Fax: 416-480-5855
alan.moody@sunnybrook.ca
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Diabetes Related Research Activities:

Diabetic patients are known to suffer an excess risk of cardiovascular disease due to atherosclerosis. Atherosclerosis is a blood vessel wall disease caused by the build-up of fatty substances called plaques. The blockage of blood flow eventually leads to serious heart and circulatory problems such as heart attack or stroke. However, diagnosis of diabetic cardiovascular disease is commonly not undertaken unless and until the patient presents with symptoms. By then, the disease is already far advanced and the potential for stabilization or reversal is limited. Although numerous imaging techniques for visualization of the diabetic blood vessel wall are available, early-stage diseases may not be easily detected. The need for developing new techniques to detect and monitor diabetic vascular disease is becoming more important as diabetes becomes more prevalent. We aim to develop MRI and ultrasound techniques for high-resolution and contrast imaging, specifically for improved characterization of vessel-wall disease in the early stages of diabetes. Our studies also aim to provide an improved understanding of the biology and interactions within the atherosclerotic plaque. This may provide a more rational and targeted approach to identify early signs of cardiovascular disease, and allow early treatment prior to significant tissue damage.

Tara Moriarty
Moriarty, Tara
PhD, BA, BSc
U Of T Appointments

Assistant Professor, Matrix Dynamics Group, Faculty of Dentistry
Assistant Professor, Department of Laboratory Medicine and Pathobiology, Faculty of Medicine

Contact Information
Fitzgerald Building, Room 241
150 College Street
Toronto, ON M5S 3E2
Phone: 416-978-6685
Fax: 416-978-5956
tara.moriarty@utoronto.ca
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Diabetes Related Research Activities:

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.

Daniel Mueller
Mueller, Daniel
MD, PhD
U Of T Appointments

Associate Profressor, Deapartment of Psychiatry

Other Appointments

Head, Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health

Contact Information
Centre for Addiction and Mental Health
250 College St., R132
Toronto, ON M5T 1R8
Phone: 416-535-8501
Fax: 416-979-4666
daniel.mueller@camh.ca
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Diabetes Related Research Activities:

The overarching goal of my research is to improve psychiatric drug treatment by implementation of personalized medicine using genetic information.

One major focus of my research is to study the genetics of antipsychotic-induced weight gain (AIWG). AIWG frequently leads to obesity and secondary conditions such as diabetes mellitus, hypertension and cardiovascular events. Our research has revealed significant associations between AIWG and polymorphisms of the Cannabinoid-1-receptor (Twari et al., 2010) gene, the melanocortin-4-receptor gene (Chowdhury et al., 2013), the Neurpeptide-Y gene (Tiwari et al., 2013) and mitochondrial genes (Goncalves et al., 2014). 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 higher risk for AIWG and diabetes, in order to select a medication panel with low risk. In addition, high risk patients will receive frequent monitoring and encouraged to enroll in diet and excercise programs.