Our Research Members

Radhakrishnan Mahadevan
Mahadevan, Radhakrishnan
U Of T Appointments

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

Contact Information
University of Toronto
Wallberg Building
200 College Street
Toronto, ON M5S 3E5
Phone: 416-946-0996
Fax: 416-978-8605
View website
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, cholesterol 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. We are also incorporating genomic information into these models and are using them to design strategies for personalized medicine.
Farid H. Mahmud
Mahmud, Farid H.
U Of T Appointments

Associate Professor, Temerty Faculty of Medicine

Other Appointments

Division of Pediatric Endocrinology, The Hospital for Sick Children

Contact Information
The Hospital for Sick Children
Division of Endocrinology
555 University Avenue
Toronto, ON M5G 1X8
Phone: 416-813-6218
Fax: 416-813-6304
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.

Vasanti Malik
Malik, Vasanti
MSc, ScD
U Of T Appointments

Assistant Professor, Department of Nutritional Sciences, Temerty Faculty of Medicine

Other Appointments

Adjunct Assistant Professor, Department of Nutrition, Harvard T.H. Chan School of Public Health

Contact Information
University of Toronto
Medical Sciences Building, 5th Floor
1 King's College Circle
Toronto, Ontario M5S 1A8
Phone: 416-978-5556
Diabetes Related Research Activities:

My research focuses on evaluating dietary and lifestyle risk factors for obesity, type 2 diabetes (T2D) and cardiovascular diseases across the life-course and in local and global populations. As a trained chronic disease epidemiologist, I use a combination of population-based approaches and lifestyle modification trials to address research questions related to the prevention of T2D, with the goal of informing public policies and dietary recommendations to promote health. I recently joined the Department of Nutritional Sciences at the University of Toronto as an Assistant Professor and hold a Tier 2 Canada Research Chair in Nutrition and Chronic Disease Prevention. I have a strong track record of publications on diet quality with an emphasis on sugary beverages and cardiometabolic health including meta-analyses and primary research studies in large cohorts. These contributions have played a vital role in guiding policies to limit intake of free sugars in Canada, the US and globally. My continued research in low- and- middle income countries has focused on reducing risk of T2D by improving the quality of carbohydrate staple foods in the diet and has now expanded to also explore food insecurity. Among my more recent research activities, I am exploring ethnic differences in cardiometabolic risk among Canadian children to help inform clinical practice guidelines and am exploring the extent to which cardiometabolic health and environmental sustainability are compatible goals when defining optimal diets at different life stages using provincial and national data. I am currently a co-Investigator on a CIHR-funded trial to improve beverage quality in children in Quebec and a National Institutes of Health-funded trial to replace sugar sweetened beverages with noncaloric beverages on obesity and cardiometabolic risk factors in adults.

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

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

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: 416-864-3028
Fax: 416-864-5904
View website
Diabetes Related Research Activities:

I currently lead the Li Ka Shing Centre for Healthcare Analytics Research and Training (LKS-CHART) of St. Michael’s Hospital. The LKS-CHART is composed of a team of data scientists with expertise in biostatistics, computer science (with a focus on machine learning, deep learning, and natural language processing), and operations research engineering (with a focus on simulation modeling and optimization). Our team works closely with clinicians and hospital management to solve ‘real world’ problems with advanced analytics. For example, the LKS-CHART team has recently developed a machine learning algorithm that constantly monitors inpatients with diabetes to predict hypoglycemic events in advance so clinicians can proactively manage patients more effectively. 

Tracy McGaha
McGaha, Tracy
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.
Toronto, ON M5G 2M9
Phone: 416-634-7252
View website
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
399 Bathurst Street
Toronto, ON M5T 2S9
Phone: 416-603-5279
Fax: 416-603-5368
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.

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

Associate Professor, Faculty of Dentistry
Associate Professor, Temerty Faculty of Medicine (Laboratory Medicine & Pathobiology)

Contact Information
Faculty of Dentistry
124 Edward Street
Toronto, ON M5G 1G6
Phone: 416-978-6685
View website
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
U Of T Appointments

Professor, Departments of Psychiatry and Pharmacology & Toxicology

Other Appointments

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

Contact Information
Centre for Addiction and Mental Health
250 College St.
Toronto, ON M5T 1R8
Phone: 416-535-8501
Fax: 416-979-4666
View website
Diabetes Related Research Activities:

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.