Polylactosamine glycosylation in lung type II epithelial cells following transfection with G1cNAc-TV

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Experimental manipulation of radiographic density in mouse mammary gland

INTRODUCTION: Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density. METHODS: We performed individual manipulations of the stromal, epithelial and matrix components of the mouse mammary gland and examined the alterations using in vivo and ex vivo radiology, whole mount staining and histology. RESULTS: Areas of density were generated that resembled densities in mammographic images of the human breast, and the nature of the imposed changes was confirmed at the cellular level. Furthermore, two genetic models, one deficient in epithelial structure (Pten conditional tissue specific knockout) and one with hyperplastic epithelium and mammary tumors (MMTV-PyMT), were used to examine radiographic density. CONCLUSION: Our data show the feasibility of altering and imaging mouse mammary gland radiographic density by experimental and genetic means, providing the first step toward modelling the biological processes that are responsible for mammographic density in the mouse

Forging Paths to Enhanced Innovation

Report of the Workshop for academia, education, business, industry, government and NGOs/not-for-profit hosted by Dr. Imogen R. Coe, Dean, Faculty of Science, Ryerson University & Dr. Mehrdad Hariri, President, CSPC. </p

Researchers’ Response to Canada’s Fundamental Science Review

Report produced following summit organized by Dr. Imogen R. Coe (Ryerson University), Dr. Jim Woodgett (Lunenfeld-Tanenbaum Research Institute) and Dr. Mehrdad Hariri (CSPC).</p

Realizing the Promise of Disaggregated Data and Analytics for Social Justice Through Community Engagement and Intersectoral Research Partnerships

In Canada, community and policy leaders have issued urgent calls to collect, analyze, and mobilize disaggregated data to inform equity-oriented initiatives aimed at addressing systemic racism and gender inequity, as well as other social inequities. This essay presents critical reflections from a national Roundtable discussion regarding how meaningful community engagement within academia–community–government research collaborations offers the opportunity to harness disaggregated data and advanced analytics to centre and address the priorities of equity-deserving and sovereignty-seeking groups. Participants emphasized four key priorities: (1) Building equitable and engaged partnerships that centre community-driven priorities and address structural barriers to community engagement; (2) Co-creating ethical data governance policies and infrastructure to support community data ownership and access; (3) Stimulating innovation and pursuing community involvement to create contextualized, advanced analyses and effective visualizations of disaggregated data; and (4) Building the capacity of all partners to effectively contribute to partnership goals. Capacity building was viewed as a bridge across a diversity of lived and professional expertise, enabling intersectoral research teams to collaborate in culturally safe and respectful ways. Beyond identifying key structural barriers impeding the promise of disaggregated data, we present practical opportunities for innovation in community-engaged scholarship to address social justice challenges in Canada

Simultaneous Transforming Growth Factor β-Tumor Necrosis Factor Activation and Cross-talk Cause Aberrant Remodeling Response and Myocardial Fibrosis in Timp3-deficient Heart*

The pleiotropic cytokines, transforming growth factor β1 (TGFβ1), and tumor necrosis factor (TNF) play critical roles in tissue homeostasis in response to injury and are implicated in multiple human diseases and cancer. We reported that the loss of Timp3 (tissue inhibitor of metalloproteinase 3) leads to abnormal TNF signaling and cardiovascular function. Here we show that parallel deregulation of TGFβ1 and TNF signaling in Timp3−/− mice amplifies their cross-talk at the onset of cardiac response to mechanical stress (pressure overload), resulting in fibrosis and early heart failure. Microarray analysis showed a distinct gene expression profile in Timp3−/− hearts, highlighting activation of TGFβ1 signaling as a potential mechanism underlying fibrosis. Neonatal cardiomyocyte-cardiofibroblast co-cultures were established to measure fibrogenic response to agonists known to be induced following mechanical stress in vivo. A stronger response occurred in neonatal Timp3−/− co-cultures, as determined by increased Smad signaling and collagen expression, due to increased TNF processing and precocious proteolytic maturation of TGFβ1 to its active form. The relationship between TGFβ1 and TNF was dissected using genetic and pharmacological manipulations. Timp3−/−/Tnf−/− mice had lower TGFβ1 than Timp3−/−, and anti-TGFβ1 antibody (1D11) negated the abnormal TNF response, indicating their reciprocal stimulatory effects, with each manipulation abolishing fibrosis and improving heart function. Thus, TIMP3 is a common innate regulator of TGFβ1 and TNF in tissue response to injury. The matrix-bound TIMP3 balances the anti-inflammatory and proinflammatory processes toward constructive tissue remodeling