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Advanced Center for Chronic Diseases

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Presentation on theme: "Advanced Center for Chronic Diseases"— Presentation transcript:

1 Advanced Center for Chronic Diseases
ACC Advanced Center for Chronic Diseases

2 Impact of the Scientific Problem: Chile’s Population
Population Structure Mortality by Cause 1990 2010 Percentage Males Females Life expectancy 74.3 79.1 % population growth 1.6 0.9 Infant mortality rate 23.6 7.4 Cancer 24.6 Cardiovascular diseases 27.7 Prevalence of Chronic Conditions National Heath Survey (%) High Blood Pressure 29.2 Smoking 41.0 Overweight 39.3 Diabetes Mellitus 9.4 Sedentarism 88.6 High Cholesterol 38.5 High CV Risk 17.7 Salt intake > 5 g/day 99.0 High risk alcohol consumption (EBBA) Cognitive impairment among >60 years 10.4 The economy of Chile is ranked as a high-income economy by the World Bank,[15] and is considered one of South America's most stable and prosperous nations,[16] leading Latin American nations in human development, competitiveness, income per capita, globalization, economic freedom, and low perception of corruption.[17] However, it has a high economic inequality, as measured by the Gini index,[18] but at regional level, Chile is ranked in the regional mean.[19] In May 2010 Chile became the first South American country to join the OECD.[20] In 2006, Chile became the country with the highest nominal GDP per capita in Latin America.[21] 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.[22] 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.[21] 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.[11] The privatized national pension system (AFP) has encouraged domestic investment and contributed to an estimated total domestic savings rate of approximately 21% of GDP.[23]

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 CORE EPIDEMIOL CORE CLINICAL 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 40% 60% 25% foreigners + 14 Associated Investigators (AIs) = 20 Average age 48 yrs 12 Postdocs 38 PhDs 5 MSc 9 Undergraduate students 10 Professionals 13 Technicians = 87 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, 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 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 Aims: 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. Molina 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).

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 of cardiovascular diseases Aim 1 Mitochondrial dynamics in the control of cardiomyocyte/vascular smooth muscle cell metabolism and remodeling. Aim 2 Mitochondrial-endoplasmic reticulum interaction in the control of cardiomyocyte/VSMC metabolism and remodeling. Cell primary cultures WT & KO mice Aim 3 Signaling pathways controlling metabolism in cardiomyocyte/VSMC by Angiotensin-(1-9) and insulin. Aim 4 Prognostic value of IGF-1, insulin, GLP-1 and exosomes in the incidence of cardiovascular diseases in MAUCO. AT2R IR MAPKs Akt Ca2+ ? Ang-(1-9) Insulin Molina

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 remodeling Cardiomyocyte primary culture To evaluate the role of galectin-3 on mitochondrial morphology and metabolism in cultured cardiomyocytes Aim 1 Murine severe TAC model The effect of pharmacological and genetic modulation of galectin-3 in a murine model of heart failure Aim 2 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 Aim 3 Emerging biomarkers in predicting adverse cardiovascular events in general population, using the Maule cohort (MAUCO) General population Aim 4 Molina

9 Andrew Quest (PI), Lisette Leyton (AI), Carmen Romero (AI)
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 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 Aim 1 Cell culture Chick CAM assay Aim 2 Murine tumor model Aim 3 MAUCO Molina In 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 carcinoma Aim 1 Role of coding/noncoding genes associated with vascularogenic mimicry and stemness in tumor dissemination at dysplasia Biomarkers Aim 2 Reprimo methylation is a plasma biomarker for early stages of gastric cancer development (dysplasia) Aim 3 Potential biomarkers of the process of tumor dissemination at dysplasia Vascularogenic mimicry and stemness are key events at early stages of gastric cancer development (dysplasia) Tumor dissemination on isolated circulating tumor cells from dysplasia Aim 4 Diagnostic value of plasmatic levels of specific microRNA in the screening of gastric cancer in the Maule cohort Aim 5 Presence of a lumen

11 Line 5: Natural History of Gallbladder Cancer (GBC) Catterina Ferreccio (PI), Juan Carlos Roa (AI), Sandra Cortés (AI) GBC prevalence - + 20 10 2000 2005 2010 The risk of developing GBC is associated with inflammatory markers Aim 1 The risk of developing GBC is associated with chronic infection by enterobacteria Aim 2 Santiago MAUCO Genetic polymorphisms and Amerindian markers are associated with metabolic inflammation and GBC Aim 3 Gallbladder 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 4 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.

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

13 ACCDiS Facilities

14 Core Facility 1: MAUCO Biobank and Databank

15 Core Facility 2: Inflammation and microRNAs

16 Core Facility 3: Functional & Experimental Animal Facility

17 Advanced Human Capital Training
To contribute actively to training and formation of young Chilean scientists, MDs and other health professionals in chronic diseases Seminars Workshops Summer courses Health professionals training PhD & MSc Thesis Co-direction Postdocs Co-direction Training opportunities in our international-national network Activities in 8 national PhD programs: Regular courses The 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 5 Establish the first PhD program in Epidemiology in Chile Undergraduate courses and training Some 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. 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 CANCER AREA National Cancer Institute, NIH University of Alberta The University of Western Australia Vanderbilt University-Nashville CARDIOVASCULAR AREA University of Texas Southwestern Medical Center- Dallas Emory School of Medicine-Atlanta The Hatter Cardiovascular Institute, UCL, London NANOBIOMEDICINE AREA Institute of Biomedical Research- Barcelona Institute of Bioengineering of Catalonia Universidad Nacional de Córdoba EPIDEMIOLOGY AREA Johns Hopkins School of Medicine-Baltimore London School of Hygiene & Tropical Medicine University of Wisconsin-Madison University of California-Berkeley CELL BIOLOGY AREA Universidade de São Paulo Mount Sinai School of Medicine- New York the 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 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 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)

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 Outreach We 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 coffee 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) With our outreach activities we aspire to communicating to the non-specialized community knowledge and understanding concerning the chronic disease “epidemic” of this century. We will focus on the transfer of knowledge concerning cancer and cardiovascular diseases, the most frequent causes of death. Additionally, we will hire a professional agency to communicate all translational insights to officials and the general population (see below). In Web page - Social Networks Hiring of communications and media training consultants 22 22

23 Baseline Average last 5 years
Selected Indicators Indicator Baseline Average last 5 years 3 years 5 years Cumulative Number of ISI Publications 43 135 230 Cumulative number of ISI publications at the top 10% of impact for the Center’s primary disciplines 4 14 25 Average impact of publications 4.5 4.8 5.0 Patent application  1 1 2 New Hires Postdoctoral Fellows 10 19 Finished PhD Thesis 33 57 Indexed publications among members of every line of research 5 24 50 Number of post-graduate theses tutored among the members of each line of research <1 9 15 Joint publications with international institutions or research centers 40 70 Joint projects with international institutions or research centers 8 Visiting researchers 3 12 20 International Workshops or Meetings in Chile, organized by the Center 7 Outreach articles Outreach events (conferences, seminars, workshops, exhibitions) Research Technology transfer Formation of advanced human resources The predicted outcome of ACCDiS productivity will focus on excellence in research (30 scientific manuscripts per year, ISI 4.5) and in the formation of advanced human resources at the undergraduate, post-graduate and post-doctoral levels. Collaboration Outreach

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