SaMi-Trop - Sao Paulo-Minas Gerais Tropical Medicine Research Center
Center Program OverviewThe Sao Paulo-Minas Gerais Tropical Medicine Research Center (SaMi-Trop) consists of a network of collaborating scientists in the States of Minas Gerais and Sao Paulo which has been established for the purpose of developing and conducting research projects on neglected infectious diseases in Brazil, with an initial focus on Chagas Disease biomarker discovery and validation. For the past 5 years, the group has worked together on the development of a Chagas Natural History Study as part of the international REDS II program supported by the NHLBI. A total of 1100 Chagas patients and controls were enrolled and submitted to rigorous clinical and laboratory evaluation. A robust specimen repository was also established, providing the opportunity to perform additional biomarker studies using this large clinically characterized Chagas disease cohort which should enable identification of stand-alone biomarkers, as well as to combine biomarker profiles, to stage disease and predict progression. For the current study we propose to perform a broader exploratory search for new biomarkers, including mRNA expression profiling, followed by a validation process to examine the predictive value of combinations of potentially informative biomarkers, both with respect to prognostic and therapeutic monitoring utility. A key problem for reaching these goals in Brazil has been the lack of scientists trained in large scale biomarker discovery, including genomic and mRNA screening methods and related bioinformatics, especially in the infectious diseases translational research settings. The proposed activities will strengthen the 20 years of ongoing collaboration with the Blood Systems Research Institute and University of California San Francisco. Our long term goal is to establish SaMi-Trop as a Center for Excellence in Tropical Medicine and Infectious Disease Research in Latin America. We believe that by developing this project with the support of the US team we will be able to develop local capacity particularly in advanced methods in data analysis for biomarker discovery and validation. Chagas disease remains one of the most neglected diseases in the world, with recent estimates indicating 8-10 million infected people in Latin and Central America and only one marginally effective therapeutic. The lack of good biomarkers for active infection or clinical end-points poses a serious problem, both for individual patient prognosis and for assessing the performance of new drugs or other therapeutic interventions. The 2 studies we propose here are focused on discovering and validating new biomarkers for T. cruzi infection and Chagas cardiac disease. Project 1 will focus on applying gene expression tools (transcrpitome analyses) to existing whole blood RNA samples from the REDS-II cohort to discover and validate new biomarkers of active infection and disease progression. Because samples from these same cases are now being tested by a genome-wide association study (GWAS) and for a series of 20 other markers by our group and collaborators, we will be able to combine the RNA expression and other marker data to develop a multiple biomarker algorithm for staging infection/disease which can guide clinical management of seropositive patients. In Project 2 we plan to take advantage of the Public Health System in the State of Minas Gerais which captures centralized ECG data from primary care teams in 600 small cities. We plan to enroll, sample and follow 2000 Chagas disease patients who live in these endemic areas. These patients will be followed for two years for the endpoints of death or admission to a hospital for cardiac disease. The main goal is to derive and validate a simple risk score based biomarker levels and EKG findings that could identify high risk patients in order to guide therapeutic approaches and serve as a foundation for future clinical trials. For this proposal two cores will be established: the Administrative Core will be in charge of project governance, fiscal and scientific oversight and the training program; and the Database and Epidemiology Core will be responsible for subject tracking, data collection and storage, and analyses. | Sami-Trop: São Paulo-Minas Gerais Tropical Medicine Research Center |