Title: 1. Integration of ASK1 regulation with cell survival signaling networks; 2. Drug discovery approaches in the 21st century: Repurposing opportunities for oncology & neglected diseases

Presenter: Prof. Haian Fu/ Hakim DJABALLAH, Lab Member & Director

University:

1. Haian Fu, Ph.D. Professor of Pharmacology, Hematology & Medical Oncology, Director of Emory Chemical Biology Discovery Center, Emory University, Atlanta, GA, USA

2. Hakim DJABALLAH, Lab Member & Director, HTS Core Facility, Molecular Pharmacology and Chemistry Program, MSKCC, New York, USA

Time: 14:30-16:30, November 5, 2012

Venue: Room A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Cellular processes are tightly controlled through well-coordinated signaling networks that respond to conflicting cues, such as reactive oxygen species, ER stress signals, and survival factors to ensure proper cell function. Within the intracellular networks that control stress response, cell differentiation, and apoptosis, apoptosis signal-regulating kinase 1 (ASK1) plays a pivotal role as a signaling hub. ASK1 senses, processes, and transmits various environmental cues to intracellular signaling machinery, impacting both physiological and patho-physiological processes. In response to stress signals, ASK1 initiates a mitogen activated protein kinase (MAPK) signaling cascade that ultimately results in activation of jun N-terminal kinase (JNK) and p38, and their corresponding biological outputs. Importantly, pathological signals, including expanded poly-Q-induced ER stress in Huntington’s as well as stress signals in other neurodegenerative diseases, engage ASK1 in the propagation of damage signals. However, how ASK1 activity is neutralized in cells under survival conditions remains to be fully elucidated. This presentation will summarize our recent research on the identification of ASK1 regulatory proteins that integrate ASK1-mediated stress response with cell survival machinery and our progress towards the discovery of small molecule ASK1 inhibitors. - Haian Fu