Presentation on theme: "Advanced Center for Chronic Diseases"— Presentation transcript:
1 Advanced Center for Chronic Diseases ACCAdvanced Center for Chronic Diseases
2 Impact of the Scientific Problem: Chile’s Population Population StructureMortality by Cause19902010PercentageMalesFemalesLife expectancy74.379.1% population growth1.60.9Infant mortality rate23.67.4Cancer24.6Cardiovasculardiseases27.7Prevalence of Chronic ConditionsNational Heath Survey(%)High Blood Pressure29.2Smoking41.0Overweight39.3Diabetes Mellitus9.4Sedentarism88.6High Cholesterol38.5High CV Risk17.7Salt intake > 5 g/day99.0High risk alcohol consumption (EBBA)Cognitive impairment among >60 years10.4The economy of Chile is ranked as a high-income economy by the World Bank, and is considered one of South America's most stable and prosperous nations, leading Latin American nations in human development, competitiveness, income per capita, globalization, economic freedom, and low perception of corruption. However, it has a high economic inequality, as measured by the Gini index, but at regional level, Chile is ranked in the regional mean.In May 2010 Chile became the first South American country to join the OECD. In 2006, Chile became the country with the highest nominal GDP per capita in Latin America. Chile has an inequality-adjusted human development index of 0.652, compared to 0.654, and for neighbouring Uruguay, Argentina and Brazil, respectively. 5.3% of the population lives on less than US $2 a day.The Global Competitiveness Report for ranks Chile as being the 30th most competitive country in the world and the first in Latin America, well above from Brazil (56th), Mexico (60th) and Argentina which ranks 85th. The Ease of doing business index created by the World Bank lists Chile as 37th in the world that encompasses better, usually simpler, regulations for businesses and stronger protections of property rights. The privatized national pension system (AFP) has encouraged domestic investment and contributed to an estimated total domestic savings rate of approximately 21% of GDP.
3 Advanced Center for Chronic Diseases 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).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.
4 Advanced Center for Chronic Diseases BASIC COREEPIDEMIOL CORECLINICAL CORESergio LavanderoDirectorCardiovasc DisAndrew QuestPICancerMarcelo KoganPINanomedicineCatterina FerréccioDeputy DirectorEpidemiology-CancerAlejandro CorvalanPICancerPablo CastroPICardiovasc Dis40%60%25% foreigners+ 14 AssociatedInvestigators (AIs)= 20Average age48 yrs12Postdocs38PhDs5MSc9Undergraduatestudents10Professionals13Technicians= 87Previous 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, joint papers between two groups. 47 in 10% top journals, average impact factor: 4.5.
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.
6 Collaborative Research Maule Cohort (MAUCO) Rolando de la Cruz, Claudia Bambs, Pablo Toro and the six ACCDiS groupsThe 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 preventableAims: To measure at baseline and follow-up on:Risk factors: a) Socioeconomic and occupational; b) Psycho-social and lifestyle; c) Environmental; d) Chronic infections and inflammation; e) Genetic and ethnic.Health biomarkers and disease-related events: a) Cardiovascular and metabolic outcomes; b) Cancer; c) Nutrition; d) Aging; e) Respiratory diseases.MolinaMethods: 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).
7 cardiovascular diseases Line 1: Metabolism and Cardiovascular Signaling Sergio Lavandero (PI), Mario Chiong (AI), Zully Pedrozo (AI)Cardiovascular metabolism is involved in the genesis and progression ofcardiovascular diseasesAim 1Mitochondrial dynamics in the control of cardiomyocyte/vascular smooth muscle cell metabolism and remodeling.Aim 2Mitochondrial-endoplasmic reticulum interaction in the control of cardiomyocyte/VSMC metabolism and remodeling.Cell primary culturesWT & KO miceAim 3Signaling pathways controlling metabolism in cardiomyocyte/VSMC by Angiotensin-(1-9) and insulin.Aim 4Prognostic value of IGF-1, insulin, GLP-1 and exosomes in the incidence of cardiovascular diseases in MAUCO.AT2RIRMAPKsAktCa2+?Ang-(1-9)InsulinMolina
8 Line 2: Emerging Biomarkers in Heart Failure Pablo Castro (PI), Hugo Verdejo (AI), Ramón Corbalán (AI)Galectin-3 is a key biomarker in heart failure, promoting both cardiac remodeling & mitochondrial dysfunction. Decrease in galectin-3 levels prevents myocardial remodelingCardiomyocyte primary cultureTo evaluate the role of galectin-3 on mitochondrial morphology and metabolism in cultured cardiomyocytesAim 1Murine severeTAC modelThe effect of pharmacological and genetic modulation of galectin-3 in a murine model of heart failureAim 2The correlation of galectin-3 and miRNA markers with myocardial dysfunction and fibrosis in high-risk heart failure (HF) patientsMyocardial strain imaging in HF patientsAim 3Emerging biomarkers in predicting adverse cardiovascular events in general population, using the Maule cohort (MAUCO)General populationAim 4Molina
9 Andrew Quest (PI), Lisette Leyton (AI), Carmen Romero (AI) Line 3: Inflammation in Angiogenesis, Cell Migration, MetastasisAndrew Quest (PI), Lisette Leyton (AI), Carmen Romero (AI)Pro-inflammatory stimuli (Prostaglandin E2, Helicobacter pylori) promote survivin dependent tumor angiogenesis and caveolin1-enhanced metastasisSurvivin expression in tumor cells favors angiogenesis by promoting β-catenin/Tcf-Lef-dependent transcription of VEGF via a PI3K/Akt-mediated pathwayPro-inflammatory stimuli disrupt E-cadherin/caveolin-1 surface complexes and promote β-catenin/Tcf-Lef- and HIF-1α-dependent transcription of survivin, cox2 and vegfPro-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 activationAim 1Cell cultureChick CAM assayAim 2Murine tumor modelAim 3MAUCOMolinaIn the cohort, look for microRNAs specific for caveolin-1 and E-cadherin (early phase) and caveolin-1 exosomes (metastasis marker)
10 Line 4: Biomarkers for Early Detection of Gastric Tumors Alejandro Corvalan (PI), Gareth Owen (AI)To identify the early steps of gastric cancer through the detection of DNA methylation Reprimo biomarker on gastric carcinomaAim 1Role of coding/noncoding genes associated with vascularogenic mimicry and stemness in tumor dissemination at dysplasiaBiomarkersAim 2Reprimo methylation is a plasma biomarker for early stages of gastric cancer development (dysplasia)Aim 3Potential biomarkers of the process of tumor dissemination at dysplasiaVascularogenic mimicry and stemness are key events at early stages of gastric cancer development (dysplasia)Tumor dissemination on isolated circulating tumor cells from dysplasiaAim 4Diagnostic value of plasmatic levels of specific microRNA in the screening of gastric cancer in the Maule cohortAim 5Presence of a lumen
11 Line 5: Natural History of Gallbladder Cancer (GBC) Catterina Ferreccio (PI), Juan Carlos Roa (AI), Sandra Cortés (AI)GBCprevalence-+2010200020052010The risk of developing GBC is associated with inflammatory markersAim 1The risk of developing GBC is associated with chronic infection by enterobacteriaAim 2SantiagoMAUCOGenetic polymorphisms and Amerindian markers are associated with metabolic inflammation and GBCAim 3Gallbladder cancer is associated with an unique inflammatory profile, enterobacteria, genetic polymorphisms, Amerindian ancestry, chemical pollutants.Chemical pollutants in food –aflatoxins, pesticides- are risk factors of GBC.Aim 4Methods: 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.
12 Line 6: Nanomedicine & Nanotheranostics Marcelo Kogan (PI), Soledad Bollo (AI), Ignacio Moreno (AI) Aim 1Spatial and temporal release of antitumor drugsAim 2To track metastasisNanotechnology in diagnosticsand treatment of cancer and cardiovascular diseasesAim 3Targeting the heart after myocardial infarction for theranosticsAim 4To develop biosensors for highly sensitive determination of plasma biomarkers in MAUCO samplesGalectin-3 and REPRIMO by Biacore, AFM and BEAMing techniques
17 Advanced Human Capital Training To contribute actively to training and formation of young Chilean scientists, MDs and other health professionals in chronic diseasesSeminarsWorkshopsSummer coursesHealth professionalstrainingPhD & MSc ThesisCo-directionPostdocsCo-directionTraining opportunities in our international-national networkActivities in 8 national PhD programs:Regular coursesThe six PI have trained a significant number of non-joint postdocs, PhD, MS and undergraduates and all Pi they have participates actively in teaching in undergraduate and postgraduate levels. 5 transvesal post-graduate courses are currently organized and executed by the Pis in 5Establish the first PhD program in Epidemiology in ChileUndergraduatecourses and trainingSome Associate Investigators will become PIs in the second period ( )
18 Networking & Collaboration Strategy 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.NATIONALUNIVERSITIESUniversidad de TalcaPontificia Universidad Católica del MauleUniversidad de TarapacáPontificia Universidad Católica de ChileUniversidad de ChileUSACHUniversidad de ConcepciónUniversidad de la FronteraUniversidad AustralHOSPITAL & HEALTH INSTITUTIONSHospitales Dipreca, San Juan de Dios, Salvador, Sótero del RíoMinisterio de SaludHospital Regional de TemucoOTHERS RESEARCH CENTERSFONDAP Center for Genomic RegulationMillenium Biomedical Neuroscience InstituteNational Center for Genomics, Proteomics and Bioinformatics -OMICsNanotechINTERNATIONALCANCER AREANational Cancer Institute, NIHUniversity of AlbertaThe University of Western AustraliaVanderbilt University-NashvilleCARDIOVASCULAR AREAUniversity of Texas Southwestern Medical Center- DallasEmory School of Medicine-AtlantaThe Hatter Cardiovascular Institute, UCL, LondonNANOBIOMEDICINE AREAInstitute of Biomedical Research- BarcelonaInstitute of Bioengineering of CataloniaUniversidad Nacional de CórdobaEPIDEMIOLOGY AREAJohns Hopkins School of Medicine-BaltimoreLondon School of Hygiene & Tropical MedicineUniversity of Wisconsin-MadisonUniversity of California-BerkeleyCELL BIOLOGY AREAUniversidade de São PauloMount Sinai Schoolof Medicine- New Yorkthe ACCDiS group will rely on the active participation of established national (30 basic research and clinical groups) and international (13 institutions from America, Europe and Asia) networks.
19 SCIENTIFIC COMMITTEEJacque Cuzick. University of London, London, UK.John Cidlowski. National Institutes of Environmental Health Sciences, NIH, USAMariell L. Jessup. University of Pennsylvania Health System and American Heart AssociationsBalz Frei. Linus Pauling Cancer Institute (LPI). Oregon State University, Corvallis, Oregon, USANelson Duran. Universidad de Campinas, Brazil
20 ADVISORY COMMITTEEDirector ACCDiSDirector FONDAPDirector FONISSubsecretario de Salud‐ Ministerio de SaludDirector de Salud del MauleSociedad Chilena de CardiologíaCorporación Nacional del cáncer (CONAC)Organización Panamericana de la Salud (OPS)
21 INTERNATIONAL EVALUATION BOARD Holly M. Brown-Borg. University of North Dakota, USAJames Galvin. New York University, USAWilliam Haley. The University of South Florida, USAMikael Jansson. Centre for Addictions Research of British Columbia, CanadaAnne Marie Lompre. Universite Pierre et Marie Curie (UPMC), FranceJeff Sands. Emory University, USA
22 OutreachWe aspire to communicating to the non-specialized community information concerning cancer and cardiovascular diseases.Scientific Cell Biology Coffee: informal discussions about “hot topics” in cell biology over coffeeProgram of outreach activitiesCycle of conferences for general audiencesLectures at high schoolsSummer Camps for secondary school studentsChronic disease video capsules (2)Meetings with business men and politiciansParticipation in Explora (CONICYT Outreach Program)With our outreach activities we aspire to communicating to the non-specialized communityknowledge and understanding concerning the chronic disease “epidemic” of this century. We will focus onthe transfer of knowledge concerning cancer and cardiovascular diseases, the most frequent causes ofdeath.Additionally, we will hire a professional agency to communicate all translational insights to officials and the general population (see below). InWeb page - Social NetworksHiring of communications and media training consultants2222
23 Baseline Average last 5 years Selected IndicatorsIndicatorBaseline Average last 5 years3 years5 yearsCumulative Number of ISI Publications43135230Cumulative number of ISI publications at the top 10% of impact for the Center’s primary disciplines41425Average impact of publications184.108.40.206Patent application 112New HiresPostdoctoral Fellows1019Finished PhD Thesis3357Indexed publications among members of every line of research52450Number of post-graduate theses tutored among the members of each line of research<1915Joint publications with international institutions or research centers4070Joint projects with international institutions or research centers8Visiting researchers31220International Workshops or Meetings in Chile, organized by the Center7Outreach articlesOutreach events (conferences, seminars, workshops, exhibitions)ResearchTechnology transferFormation of advancedhuman resourcesThe predicted outcome of ACCDiS productivity will focus on excellence in research (30scientific manuscripts per year, ISI 4.5) and in the formation of advanced humanresources at the undergraduate, post-graduate and post-doctoral levels.CollaborationOutreach