S132: Discovery of natural product-based drugs from Costa Rica biota

This ICBG includes collaborative efforts between the Sherman group at the University of Michigan, the Clardy Group at Harvard Medical School and the Tamayo group at the National Institute for Biodiversity in Costa Rica.  A focus of the Michigan effort involves investigation of extracts from unique marine derived microorganisms, and high throughput screening at the UM Center for Chemical Genomics, HMS ICCB-L and the NIH Chemical Genomics Center.  Numerous targets against important human diseases are being pursued for identification of bioactive natural products with potential for therapeutic development.  One effort includes a target (CHOP) relevant to control of malignant cells.  This work focuses on identifying natural product molecular probes that will elucidate fundamental mechanisms regulating protein folding and the cellular responses to the accumulation of unfolded protein within the endoplasmic reticulum.  An important cardiovascular target (PAI-1) is also leading to the identification of new natural products with the potential to impact blood clotting mechanisms in human disease.  Two new antibiotic targets involving Gram-negative biofilm generating bacteria have also lead to the identification of important new natural product molecules with promising activity.  Finally, a new effort against malarial targets is providing a new paradigm for identification of natural product leads to control this deadly disease.