Informe anual 2014

INFORME ANUAL 2014 – CENTRO FONDAP ACCDIS

SCIENTIFIC SUMMARY

The Chilean population rapidly increased its life expectancy. However, an “epidemic” of risk factors for Chronic Diseases (CDs) now threatens the quality of life of its adult population.

The goals of Advanced Center for Chronic Diseases (ACCDiS) are to observe and dissect the natural history of cardiovascular diseases (CVD) and cancer in Chile. During 2014 we initiated the Maule Cohort (MAUCO), the first Chilean broad spectrum longitudinal study of CDs with a prospective follow up of risk factors and health events. MAUCO will evaluate 10,000 adult residents aged 38 years and above in the town of Molina in the Maule Region of central Chile. MAUCO´s biobank and databank together with our two core center facilities, the Functional & Experimental Animal and the Inflammation & microRNA Core Facilities, are the basis for our cross-communication and multidisciplinary approach to CDs. Complying with our strategic goal, post-docs incorporated in ACCDiS formulate proposals co-mentored by at least two research lines, from both Universities. During 2014, six new associate researchers were incorporated. The ACCDiS International Committee was constituted and includes Drs Karl T. Weber, Jack Cuzick, Gary S. Stein, Keith Burridge and Nelson Duran. They will meet annually to evaluate the Centers performance; the first meeting is scheduled for June 2015. The ACCDiS National Advisory Boardwas created and includes representatives of: ACCDiS, FONDAP, CONICYT, Foreign Affairs of the Ministry of Health, Maule Health Service, Fundación Salud y Corazón and Chilean Society of Cardiology, National Cancer Corporation (CONAC), and the Chilean Society for Epidemiology. They will meet twice a year and the first meeting is scheduled for May 2015.

Publications: we published 42 ISI papers, 7 (17%) in top ten journals and 23 (55%) papers in Q1 journals. Average ISI impact factor 5.07. Eight of 42 ISI papers (19%) were in collaboration between research lines. ACCDiS academic activities: Weekly Council meetings. Biweekly scientific seminars with national/international speakers. ACCDiS annual retreat. ACCDiS on-site visits in Molina and inauguration of MAUCO with the community (Molina Major, Minister of Health, Maule Heath Service Director, Molina Hospital Director, academics and students of Regional Universities).

International networking: 16 visits from ACCDiS members to foreign institutions and 16 international researchers visited ACCDiS in Santiago.

Advanced training of human resources directly related to ACCDiS including18 postdoctoral fellows, 45 PhD thesis students from 10 PhD Programs. Six of 18 (33%) postdoctoral fellows, 5 of 45 (11%) PhD thesis students, 1 of 9 (11%) MSc students and 1 of 12 (8%) undergraduate students were co-mentored by ACCDiS members from different research lines. ACCDiS PIs and AIs actively participated in the coordination and teaching in various PhD, MSc and undergraduate courses of both universities. MAUCO incorporated academics and under-graduate students from local universities in the field activities.

Contribution to public policies: ACCDiS/MAUCO is supported by the Ministry of Health, the Maule Health Service and the Molina Municipality.

Collaborative research projects
Core epidemiology cohort project (MAUCO). We developed the infrastructure, methods and acquired equipment, initiated the census and qualitative research, developed communication strategies, selected and trained field teams, piloted instruments and signed agreements with local institutions. A Biobank was implemented in collaboration with NCI/NIH/USA and the MAUCO Databank is housed in a dedicated new server of the Medical School of P Catholic University of Chile (PUC). We completed the census of 2,634 households, and 1,416 individuals. ACCDiS transversal collaborations will improve the cardiovascular baseline assessment by including electrocardiograms and echocardiograms and evaluating plasma biomarkers. Also the evaluation of digestive cancers risks using nanoparticles has been initiated.

Cancer & Cardiovascular: Inflammation and microRNA corein-silico analysis of miRNAs as potential markers of heart failure. Angiotensin-(1-9). Potential application as an inhibitor of metastasis. Role of caveolin-1 and PKA in the regulation of ER-mitochondria communication in cancer & in regulating autophagy in cancer cells. Cancer & Nanomedicine: nanobiotechnology to identify an aflatoxin metabolite in urine. Ultrasensitive detection of methylated reprmio. Labelling of metastatic BF1610 cells with gold nanoparticles. Polymeric nanoparticles to improve delivery of curcumin. Angiotensin-(1-9)/drug delivery. New methods to deliver angiotensin-(1-9) using nanoparticles.

Main research findings: Research Lines (RL). RL1: Insulin regulates mitochondrial morphology and metabolism in cardiomyocytes and skeletal muscle cells by the Opa1/Akt/mTOR/NFκB pathway. RL2: Trimetazidine (TMZ) added to standard treatment did not improve myocardial function. RL3: Survivin expression in tumor cells promotes VEGF synthesis and angiogenesis via PI3K/Akt-dependent activation of b-catenin-Tcf/Lef-dependent transcription. RL4: Survivin and Reprimo appear to be mutually exclusive in gastric cancer. RL5: Seven serum inflammatory markers, chronic Salmonella typhi carriage and higher aflatoxin in Gallbladder Cancer vs Gallstones or population controls. RL6: gastric cancer biomarkers (gold and silver nanoparticles, Raman reporter and plasmon-enhanced spectroscopy) and a novel carbon nanotube functionalized with oligonucleotides.

Main challenges of the first year have been the development of a common language, identifying common research questions and integrating researchers.

Main difficulties are related to the Universities significant limitations in administering the research funds, thus diverting significant time of all PIs to ressolving administrative problems often beyond our control.

Perspectives: The incorporation of a center Manager is helping us to strengthen the Centers ability to deal with these limitations and to develop a Center Strategic Plan for the next 4 years. Additionally, based on our experience in the first year, we will improve our strategies to integrate ACCDiS scientists from the basic sciences with those of clinical and public health disciplines. We will also seek additional funds to supplement our main projects allowing for more students to participate.