Title: 1.Targeting protein-protein interaction interfaces for small molecule modulator discovery; 2.Drug Resistant Tuberculosis a Global Crisis: Perceptions versus Realities

Presenter: 1. Haian Fu, Ph.D. Professor of Pharmacology; 2. Gail H. Cassell, Ph.D., D.Sc.

University: 1. Emory University, Atlanta, GA USA; 2. Harvard Medical School

Time: 9:00-12:00, June 20, 2012

Venue: Room A102, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Protein-protein interactions (PPI) dictate intricate intra- and inter-cellular signaling networks, which are essential for diverse physiological processes. Genomic alterations in cancer and other diseases are often associated with altered PPI networks, which provides molecular basis for a large number of human diseases. Thus, PPIs have emerged as a viable class of molecular targets for therapeutic interventions. However, PPI interfaces are generally considered as “undruggable” targets in part due to their large interaction areas and shallow pockets. Recent advances in high throughput screening, innovative chemistry, and computational technologies have led to the discovery of a number of PPI inhibitors for some major disease-related signaling pathways. The PPI inhibitor discovery process has further been accelerated by the NIH initiatives including the NCI Chemical Biology Consortium. PPIs have become a highly promising class of emerging drug targets with broad implications. This presentation will highlight our efforts on (i) genomics-based research that aims to bridge the genomics-therapeutics gap for new PPI target discovery and (ii) targeting PPI interfaces for small molecule modulator discovery. Targeted protein pairs in the Emory Chemical Biology Discovery Center include 14-3-3/Raf-1 in cell proliferation pathway, eIF4E/4G in translational control, and Mcl1/Noxa in apoptosis. Case studies will be presented to illustrate challenges and promises for the discovery of PPI inhibitors. ---Haian Fu

Strains of M.tb. that are resistant to the drugs conventionally used to treat TB have become well established in many countries. Accurate estimates of the prevalence of MDR, XDR, and TDR TB are not possible because of a lack of laboratory capacity in many of these countries, but current estimates are sure to be grossly understated. The number of patients receiving appropriate treatment for drug-resistant TB is distressingly small .Until recently, the perception was that resistant strains of TB were too weak to achieve high rates of transmission, and therefore that infection control was not the highest priority. However, new evidence indicates that human-to-human spread is more common than previously appreciated.-- Gail H. Cassell