Department of Pathology and Molecular Medicine Graduate Theses
Recent Submissions
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Evaluation of the hemostatic stress response in Type 1 von Willebrand Disease
Type 1 von Willebrand Disease (VWD) is an inherited bleeding disorder resulting from a quantitative deficiency in the procoagulant protein von Willebrand factor (VWF). Diagnosis is dependent on a reduction in VWF levels ... -
Identification of Novel Receptor Tyrosine Kinases Regulating the Hippo Pathway in Cancer Cells
Several studies have shown that the Hippo pathway plays an important role in tissue growth, organ size control, and cell death. Deregulation of the Hippo pathway contributes to loss of cell contact inhibition and continuing ... -
The role of von Willebrand factor in the pathogenesis of immunothrombosis
Pathologic immunothrombosis is the formation of arterial, venous or microvascular thrombi in response to dysregulated activation of the immune system. Inflammatory diseases such as sepsis and obesity are associated with a ... -
Evaluating the relationship between the RET receptor tyrosine kinase and TMEM127
Pheochromocytomas (PCC) are highly heritable neoplasms of the adrenal gland, carrying germline mutations in approximately 40% of cases. PCC susceptibility genes have been subdivided into two clusters: hypoxia-related genes, ... -
Impact of Androgen Deprivation Therapy on the Gastrointestinal Microbiota of Prostate Cancer Patients
Background: Prostate Cancer (PCa) is one of the leading causes of cancer in men. Androgen deprivation therapy (ADT), the standard of care for advanced PCa, has been associated with developing the metabolic syndrome. The ... -
Exploring the Genomic Binding Landscape of the Oncogenic Transcription Factor TCF3-PBX1 in Acute Lymphoblastic Leukemia
Treatment of acute lymphoblastic leukemia (ALL) has become quite effective over the last two decades. However, further progress is limited by a lack of understanding of the biological processes that drive this disease. ... -
The role of PPARg-dependent microRNA expression during breast tumour metastasis
Previous studies by Dr. Nicol showed the first direct in vivo evidence that peroxisome proliferator-activated receptor (PPAR)γ normally suppresses environmental chemical 7,12-dimethylbenz[a]anthracene (DMBA)-mediated breast ... -
Differential Contributions of RET-isoforms to Tumour Invasion
RET is a receptor tyrosine kinase (RTK) which is normally activated at the cell surface by glial cell line-derived neurotrophic factors and plays critical roles during embryogenesis. RET is expressed as two protein isoforms, ... -
Novel Methods of Factor VIII Tolerance Induction in Hemophilia A Mouse Models
The most serious complication of factor VIII (FVIII) replacement therapy in hemophilia A (HA) patients remains the development of anti-FVIII antibodies (inhibitors). At this time, there are no methods to prevent inhibitor ... -
Diagnostic and Prognostic Biomarkers for Early Prostate Cancer
Prostate cancer is diagnosed and treated primarily on the basis of histopathological assessment of biopsies and cancer extent. Unfortunately, this assessment, performed by pathologists on very small amounts of biopsy tissue, ... -
Characterizing the Role of the RET Receptor Tyrosine Kinase in Colorectal Cancer
RET is a receptor tyrosine kinase (RTK) that plays important roles in both normal development and cancer. RET has well-established oncogenic roles in thyroid cancer and growing evidence implicates RET activity in the ... -
Characterization of Variants of Unknown Significance (VUS) in BRCA1
Approximately 3%-8% of breast cancer patients carry one defective BRCA1 or BRCA2 allele. While the rise of genetic testing have helped identify BRCA mutation carriers, the implication of certain mutations are still unknown. ... -
Co-regulation of the Cytochrome P450 24A1 gene in a model of kidney fibrosis by 1,25-dihydroxyvitamin D3 and growth factors
Renal fibrosis is a dominant pathological characteristic of progressive Chronic Kidney Disease (CKD). Epithelial-to-Mesenchymal-Transition (EMT), triggered by tissue damage, caused by renal inflammation, initiates and ... -
Investigating the role of von Willebrand factor (VWF) in angiogenesis
Gastrointestinal bleeding from angiodysplasia can be a debilitating problem for patients with defective or deficient von Willebrand factor (VWF). Studies have pointed to a regulatory role for VWF in vessel formation however, ... -
Role of the Cadherin-11/Rac1/Stat3 Axis in Src-Mediated Transformation and in Adipocytic Differentiation
Stat3 (signal transducer and activator of transcription-3) is activated by phosphorylation on tyrosine-705 (Stat3-ptyr705) downstream of cytokines, growth factors, and oncogenes. Our lab has demonstrated that engagement ... -
Delineating Novel Genetic and MicroRNA Regulatory Mechanisms in Aggressive Subtypes of Breast Cancer
Breast cancer will be diagnosed in over 26,500 Canadians this year. Despite advances, identifying who will develop aggressive breast tumours or who will respond to treatment remains a clinical challenge. This dissertation ... -
The regions connecting the membrane spanning and nucleotide binding domains of MRP1 are functionally distinct
Multidrug resistance protein 1 (MRP1) is a 190 kDa ATP-binding cassette transporter which effluxes xeno- and endobiotic organic anions including estradiol glucuronide (E217βG) and the pro-inflammatory leukotriene C4 (LTC4). ... -
Evaluating the pre-B-cell receptor as a potential mediator of leukemogenesis downstream of the TCF3-PBX1 oncogenic transcription factor
Approximately 5% of B-progenitor acute lymphoblastic leukemia (B-ALL) harbor a somatic 1;19 chromosomal translocation which generates a fusion gene coding for TCF3-PBX1. Recent studies have shown that leukemic progenitors ... -
Calpain-1 and Calpain-2 Promote HER2/NEU Tumorigenesis and Independently Promote Metastasis in Triple Negative Breast Cancer
Calpains are a family of calcium activated cysteine proteases. Calpain-1 and calpain-2 are obligate heterodimers composed of isoform specific catalytic subunits (encoded by capn1 and capn2, respectively) coupled with the ... -
The role of extracellular vesicles in the transfer of multidrug resistance in human ovarian cancer cells
Ovarian cancer is the fifth most common cancer in Canadian women and has the highest mortality rate of all gynecologic malignancies. First-line treatment is typically cytoreductive surgery followed by a combination of ...