Non-communicable diseases (NCDs) are currently the leading cause of death worldwide. In this project, we propose to study basic mechanisms underlying the development of cancer, cardiovascular diseases and diabetes, pathologies which together account for roughly 50% of total deaths in Chile. To do so, the RING group called “NEMESIS” (Network for Metabolic Stress Signaling), including 6 experienced and 6 more junior investigators was created. The 3 principal investigators (PIs) previously worked together (2002-2012) as part of the Center for Molecular Studies of the Cell (CEMC), which focused on studying cell signaling events. All associate investigators have worked previously with these PIs in the CEMC framework and contributed to an extraordinary number of publications (total 137/average ISI: 4.3) with notable areas of overlapping interest (joint publications 59) that are now the focus of this highly interdisciplinary RING.
Research
An important novel aspect of NEMESIS is that the group seeks to provide answers to how cells respond to different types of “metabolic stress”. Accordingly, the scientific objectives of this project will investigate how “pathological stress signals” (including hypoxia, nutrient deprivation or excess and neurohumoral agents) impinge on cancer cells, cardiomyocytes, skeletal muscle cells and pancreatic b-cells to generate metabolic stress signaling (for instance, via formation of reactive oxygen and nitrogen species) and contribute to the development of disease. To gain insight to such questions, 6 scientific specific aims will be analyzed: 1) Caveolin-1 as a negative regulator of HIF-1a; 2) Regulation of autophagy in cardiomyocytes; 3) Skeletal muscle adaptation to lipotoxicity and insulin resistance; 4) Alterations in intraorganelle communication under stress conditions; 5) Lipotoxicity and insulin resistance in heart and pancreatic b-cells and 6) Stress-induced muscle wasting. Answering these questions will yield significant new insight to cancer, cardiovascular diseases and diabetes. To address these issues, standard approaches analyzing cells in vitro will be combined with the use of appropriate animal models to corroborate insights in vivo and in some cases with the analysis of samples from human patients.
NEMESIS will provide a broader understanding of three important NCDs in Chile by developing:
- A research program of excellence involving collaborations at the national and international level;
- An extensive training program for students at the undergraduate, masters, graduate and post-doctoral level;
- An interdisciplinary research environment within a well-developed network of national and international laboratories that fosters the development of younger associates;
- An outreach program that seeks to connect basic scientists to society.
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