Profiles of BBDC Members Primarily Involved In Diabetes Research

Search for Name or Keyword


McGaha, Tracy - PhD, MS, BS

University of Toronto Appointment(s): Associate Professor, Department of Immunology

Other Appointment(s): 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

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. 

View Publications

McIntyre, Roger S.

University of Toronto Appointment(s): Associate Professor of Psychiatry and Pharmacology

Other Appointment(s): 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

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.

View Publications

Moody, Alan - MBBS, FRCP, FRCR

University of Toronto Appointment(s): Professor, Department of Medical Imaging
Associate Professor, Department of Medical Biophysics
Full member Institute of Medical Sciences
Chair, Department of Medical Imaging

Other Appointment(s): Senior Scientist, Sunnybrook Research Institute
Staff Radiologist, Sunnybrook Health Sciences Centre

Contact Information:
Department of Medical Imaging
Toronto, ON

Phone: (416) 978-0511
Fax: (416) 978-6915

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.

View Publications

Moriarty, Tara - PhD, BA, BSc

University of Toronto Appointment(s): 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

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.

View Publications

Mueller, Daniel - MD, PhD

University of Toronto Appointment(s): Associate Profressor, Deapartment of Psychiatry

Other Appointment(s): 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

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.

View Publications

Records 76 to 80 of 133
<< < 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 > >> page(s)