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Advanced Center for Chronic Diseases 1. Cancer 24.6 Impact of the Scientific Problem: Chile’s Population (%) High Blood Pressure29.2 Smoking41.0 Overweight39.3.

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Presentation on theme: "Advanced Center for Chronic Diseases 1. Cancer 24.6 Impact of the Scientific Problem: Chile’s Population (%) High Blood Pressure29.2 Smoking41.0 Overweight39.3."— Presentation transcript:

1 Advanced Center for Chronic Diseases 1

2 Cancer 24.6 Impact of the Scientific Problem: Chile’s Population (%) High Blood Pressure29.2 Smoking41.0 Overweight39.3 Diabetes Mellitus9.4 Sedentarism88.6 High Cholesterol38.5 High CV Risk17.7 Salt intake > 5 g/day99.0 High risk alcohol consumption (EBBA)17.7 Cognitive impairment among >60 years 10.4 Population Structure Percentage Males Females Percentage Males Females Mortality by Cause Prevalence of Chronic Conditions National Heath Survey Cardiovascular diseases 27.7 Life expectancy % population growth Infant mortality rate

3 Specific Aims:  To develop a multidisciplinary research initiative that will permit analyzing the natural history of cardiovascular diseases and cancer in the Chilean population.  To establish specific research lines in the area of cancer and cardiovascular diseases covering basic, clinical and epidemiological aspects and their public health consequences.  To set up novel common facilities that provide state of the art support for the basic, clinical and epidemiological research and training units.  To train advanced human resources in CDs in collaboration with our international partners.  To communicate to the general public CD-related information and educate in disease prevention. General Aim: To provide a framework for the understanding and prevention of the two main chronic diseases affecting the Chilean population. In association with a network of international collaborators, ACCDiS aspires to becoming a reference center in Latin America for research and advanced training in chronic diseases (CDs). Advanced Center for Chronic Diseases 3

4 Previous collaborative interactions : Grants: AQ-SL (FONDAP CEMC, Ring), CF-AC (FONDEF grant), SL-PC (FONDECYTs), etc. Papers: High level productivity (last 5 years): 215 papers in peer-reviewed journals, 23 joint papers between two groups. 47 in 10% top journals, average impact factor: 4.5. BASIC COREEPIDEMIOL CORECLINICAL CORE Sergio Lavandero Director Cardiovasc Dis Andrew Quest PI Cancer Marcelo Kogan PI Nanomedicine Catterina Ferréccio Deputy Director Epidemiology-Cancer Alejandro Corvalan PI Cancer Pablo Castro PI Cardiovasc Dis = Technicians 10 Professionals 9 Undergraduate students 38 PhDs 5 MSc 12 Postdocs + 14 Associated Investigators (AIs) 40% 60% Average age 48 yrs 25% foreigners = 20 Advanced Center for Chronic Diseases 4

5 Facultad de Ciencias Químicas y Farmacéuticas Sergio Lavandero. Depto de Bioquímica y Biología Molecular. Marcelo Kogan. Depto de Química Farmacológica y Toxicológica. Andrew Quest. Depto de Bioquímica y Biología Molecular. Guillermo Díaz. Depto de Química Farmacológica y Toxicológica. Lorena García. Depto de Bioquímica y Biología Molecular. Soledad Bollo. Depto de Química Farmacológica y Toxicológica. Carmen Romero. Depto de Bioquímica y Biología Molecular. Felipe Oyarzún. Depto de Ciencias y Tecnología Farmacéuticas. Mario Chiong. Depto de Bioquímica y Biología Molecular. 5

6 Molina Collaborative Research Maule Cohort (MAUCO) Rolando de la Cruz, Claudia Bambs, Pablo Toro and the six ACCDiS groups The epidemic of chronic diseases is associated with lifestyle and environmental changes and interactions with the genetic background of the population, which create unique disease profiles. The county of Molina (Maule region) with a high burden of chronic diseases is an ideal setting for population-based studies designed to identify key factors involved in disease development. Chronic diseases share common risk factors and most of them are preventable Methods: Population-based prospective cohort of 10,000 subjects aged >45 yrs, residents of Molina county. Collect biological samples and conduct an epidemiological survey (Biobank and Databank). Aims: To measure at baseline and follow-up on: 1.Risk factors: a) Socioeconomic and occupational; b) Psycho-social and lifestyle; c) Environmental; d) Chronic infections and inflammation; e) Genetic and ethnic. 2.Health biomarkers and disease-related events: a) Cardiovascular and metabolic outcomes; b) Cancer; c) Nutrition; d) Aging; e) Respiratory diseases. 6

7 Line 1: Metabolism and Cardiovascular Signaling Sergio Lavandero (PI), Mario Chiong (AI), Zully Pedrozo (AI) Mitochondrial dynamics in the control of cardiomyocyte/vascular smooth muscle cell metabolism and remodeling. Mitochondrial-endoplasmic reticulum interaction in the control of cardiomyocyte/VSMC metabolism and remodeling. Signaling pathways controlling metabolism in cardiomyocyte/VSMC by Angiotensin-(1-9) and insulin. Prognostic value of IGF-1, insulin, GLP-1 and exosomes in the incidence of cardiovascular diseases in MAUCO. Cardiovascular metabolism is involved in the genesis and progression of cardiovascular diseases AT2R IR MAPKsAktCa 2+ ? ? Ang-(1-9)Insulin Molina Aim 1Aim 2 Aim 3Aim 4 Cell primary cultures WT & KO mice 7

8 Line 2: Emerging Biomarkers in Heart Failure Pablo Castro (PI), Hugo Verdejo (AI), Ramón Corbalán (AI) Cardiomyocyte primary culture Aim 1 Aim 2 Aim 3 Aim 4 To evaluate the role of galectin-3 on mitochondrial morphology and metabolism in cultured cardiomyocytes The effect of pharmacological and genetic modulation of galectin-3 in a murine model of heart failure Murine severe TAC model The correlation of galectin-3 and miRNA markers with myocardial dysfunction and fibrosis in high- risk heart failure (HF) patients Myocardial strain imaging in HF patients Emerging biomarkers in predicting adverse cardiovascular events in general population, using the Maule cohort (MAUCO) General population Galectin-3 is a key biomarker in heart failure, promoting both cardiac remodeling & mitochondrial dysfunction. Decrease in galectin-3 levels prevents myocardial remodeling Molina 8

9 Survivin expression in tumor cells favors angiogenesis by promoting β-catenin/Tcf-Lef-dependent transcription of VEGF via a PI3K/Akt-mediated pathway Pro-inflammatory stimuli disrupt E-cadherin/caveolin-1 surface complexes and promote β-catenin/Tcf-Lef- and HIF-1α-dependent transcription of survivin, cox2 and vegf Pro-inflammatory stimuli activate NADPH oxidases and Src-family kinases, liberate caveolin-1 from E- cadherin/caveolin-1 surface complexes and promote migration/invasion via caveolin-1 enhanced tyrosine-14 phosphorylation and Rac1 activation Line 3: Inflammation in Angiogenesis, Cell Migration, Metastasis Andrew Quest (PI), Lisette Leyton (AI), Carmen Romero (AI) Pro-inflammatory stimuli (Prostaglandin E2, Helicobacter pylori) promote survivin dependent tumor angiogenesis and caveolin1-enhanced metastasis Aim 1 Aim 2 Aim 3 Cell culture Murine tumor model MAUCO Molina In the cohort, look for microRNAs specific for caveolin-1 and E-cadherin (early phase) and caveolin-1 exosomes (metastasis marker) Chick CAM assay 9

10 Reprimo methylation is a plasma biomarker for early stages of gastric cancer development (dysplasia) Aim 1 Aim 2 Aim 3 Vascularogenic mimicry and stemness are key events at early stages of gastric cancer development (dysplasia) Line 4: Biomarkers for Early Detection of Gastric Tumors Alejandro Corvalan (PI), Gareth Owen (AI) Aim 4 Aim 5 Biomarkers To identify the early steps of gastric cancer through the detection of DNA methylation Reprimo biomarker on gastric carcinoma Role of coding/noncoding genes associated with vascularogenic mimicry and stemness in tumor dissemination at dysplasia Potential biomarkers of the process of tumor dissemination at dysplasia Tumor dissemination on isolated circulating tumor cells from dysplasia Diagnostic value of plasmatic levels of specific microRNA in the screening of gastric cancer in the Maule cohort Presence of a lumen 10

11 Line 5: Natural History of Gallbladder Cancer (GBC) Catterina Ferreccio (PI), Juan Carlos Roa (AI), Sandra Cortés (AI) Methods: 1,000 people at higher risk gallbladder cancer from MAUCO. GB disease (10%), altered lipids (20%), diabetes (7%), obesity (30%) will be followed with abdominal Sonograph, samples of blood, urine and stool, identifying occurrence of disease. Gallbladder cancer is associated with an unique inflammatory profile, enterobacteria, genetic polymorphisms, Amerindian ancestry, chemical pollutants. The risk of developing GBC is associated with inflammatory markers Aim 1 Aim 2 Aim 3 Aim 4 The risk of developing GBC is associated with chronic infection by enterobacteria Genetic polymorphisms and Amerindian markers are associated with metabolic inflammation and GBC Chemical pollutants in food – aflatoxins, pesticides- are risk factors of GBC MAUCO Santiago GBC prevalence -+ 11

12 Line 6: Nanomedicine & Nanotheranostics Marcelo Kogan (PI), Soledad Bollo (AI), Ignacio Moreno (AI) To track metastasis Spatial and temporal release of antitumor drugs Targeting the heart after myocardial infarction for theranostics Galectin-3 and REPRIMO by Biacore, AFM and BEAMing techniques Nanotechnology in diagnostics and treatment of cancer and cardiovascular diseases To develop biosensors for highly sensitive determination of plasma biomarkers in MAUCO samples Aim 1 Aim 2 Aim 3Aim 4 12

13 ACCDiS Facilities 13

14 Core Facility 1: MAUCO Biobank and Databank Molina

15 Core Facility 2: Inflammation and microRNAs

16 Core Facility 3: Functional & Experimental Animal Facility

17 Advanced Human Capital Training Establish the first PhD program in Epidemiology in Chile Activities in 8 national PhD programs: Regular courses PhD & MSc Thesis Co-direction Health professionals training Seminars Workshops Summer courses Postdocs Co-direction Training opportunities in our international- national network Some Associate Investigators will become PIs in the second period ( ) To contribute actively to training and formation of young Chilean scientists, MDs and other health professionals in chronic diseases Undergraduate courses and training 17

18 Networking & Collaboration Strategy CANCER AREA 1.National Cancer Institute, NIH 2.University of Alberta 3.The University of Western Australia 4.Vanderbilt University- Nashville CARDIOVASCULAR AREA 5.University of Texas Southwestern Medical Center- Dallas 6.Emory School of Medicine- Atlanta 7.The Hatter Cardiovascular Institute, UCL, London NANOBIOMEDICINE AREA 8.Institute of Biomedical Research- Barcelona 9.Institute of Bioengineering of Catalonia 10.Universidad Nacional de Córdoba EPIDEMIOLOGY AREA 11.Johns Hopkins School of Medicine-Baltimore 12.London School of Hygiene & Tropical Medicine 13.University of Wisconsin- Madison 14.University of California-Berkeley CELL BIOLOGY AREA 15.Universidade de São Paulo 16.Mount Sinai School of Medicine- New York NATIONAL UNIVERSITIES Universidad de Talca Pontificia Universidad Católica del Maule Universidad de Tarapacá Pontificia Universidad Católica de Chile Universidad de Chile USACH Universidad de Concepción Universidad de la Frontera Universidad Austral HOSPITAL & HEALTH INSTITUTIONS Hospitales Dipreca, San Juan de Dios, Salvador, Sótero del Río Ministerio de Salud Hospital Regional de Temuco OTHERS RESEARCH CENTERS FONDAP Center for Genomic Regulation Millenium Biomedical Neuroscience Institute National Center for Genomics, Proteomics and Bioinformatics -OMICs Nanotech INTERNATIONAL Establish national and international collaborations with individual groups, research centers & institutions. Actions: collaborative research, co-direction PhD theses- postdocs, joint papers, courses, conferences and symposia. 18

19 19 SCIENTIFIC COMMITTEE Jacque Cuzick. University of London, London, UK. John Cidlowski. National Institutes of Environmental Health Sciences, NIH, USA Mariell L. Jessup. University of Pennsylvania Health System and American Heart Associations Balz Frei. Linus Pauling Cancer Institute (LPI). Oregon State University, Corvallis, Oregon, USA Nelson Duran. Universidad de Campinas, Brazil

20 20 ADVISORY COMMITTEE Director ACCDiS Director FONDAP Director FONIS Subsecretario de Salud ‐ Ministerio de Salud Director de Salud del Maule Sociedad Chilena de Cardiología Corporación Nacional del cáncer (CONAC) Organización Panamericana de la Salud (OPS)

21 21 INTERNATIONAL EVALUATION BOARD Holly M. Brown-Borg. University of North Dakota, USA James Galvin. New York University, USA William Haley. The University of South Florida, USA Mikael Jansson. Centre for Addictions Research of British Columbia, Canada Anne Marie Lompre. Universite Pierre et Marie Curie (UPMC), France Jeff Sands. Emory University, USA

22 Scientific Cell Biology Coffee: informal discussions about “hot topics” in cell biology over coffee Outreach Program of outreach activities  Cycle of conferences for general audiences  Lectures at high schools  Summer Camps for secondary school students  Chronic disease video capsules (2)  Meetings with business men and politicians  Participation in Explora (CONICYT Outreach Program) We aspire to communicating to the non-specialized community information concerning cancer and cardiovascular diseases.  Web page - Social Networks  Hiring of communications and media training consultants 22

23 Selected Indicators IndicatorBaseline Average last 5 years 3 years5 years Cumulative Number of ISI Publications Cumulative number of ISI publications at the top 10% of impact for the Center’s primary disciplines Average impact of publications Patent application  1 1 12 New Hires024 Postdoctoral Fellows21019 Finished PhD Thesis Indexed publications among members of every line of research52450 Number of post-graduate theses tutored among the members of each line of research <1915 Joint publications with international institutions or research centers Joint projects with international institutions or research centers2814 Visiting researchers31220 International Workshops or Meetings in Chile, organized by the Center 2712 Outreach articles1715 Outreach events (conferences, seminars, workshops, exhibitions)31425 Research Collaboration Formation of advanced human resources Outreach Technology transfer 23


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