Enhancing ATG-dependent Defense Against Pathogens w/Therapeutics Lead CP

$2,096,875U19FY2015AINIH

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Paper 37905813 Paper 37392388 Paper 36419223 Paper 35800386 Paper 34403684 Paper 34320354 Paper 33495338 Paper 33384352 Paper 33372156 Paper 33328639 Paper 33222586 Paper 33176151 Paper 33087464 Paper 33024031 Paper 32051584 Paper 31959973 Paper 31941841 Paper 31919280 Paper 31346084 Paper 31130511 Paper 31059511 Paper 30633901 Paper 30409884 Paper 30349087 Paper 30335568 Paper 30209176 Paper 30194229 Paper 30150136 Paper 30127493 Paper 30126924 Paper 30118219 Paper 30058798 Paper 29998728 Paper 29878747 Paper 29849149 Paper 29650672 Paper 29590614 Paper 29496999 Paper 29420262 Paper 29185708 Paper 29165043 Paper 29130415 Paper 29066772 Paper 29031786 Paper 28973896 Paper 28966054 Paper 28910640 Paper 28877469 Paper 28876241 Paper 28872463 Paper 28811338 Paper 28806762 Paper 28802038 Paper 28783698 Paper 28751470 Paper 28698274 Paper 28529316 Paper 28414223 Paper 28327616 Paper 28218432 Paper 28110145 Paper 28077655 Paper 28039434 Paper 28017659 Paper 28017329 Paper 27974209 Paper 27880896 Paper 27879260 Paper 27831741 Paper 27827795 Paper 27586339 Paper 27551152 Paper 27540007 Paper 27463423 Paper 27452467 Paper 27411589 Paper 27351204 Paper 27327515 Paper 27287411 Paper 27273576 Paper 27230380 Paper 27211859 Paper 27183573 Paper 27133164 Paper 27096368 Paper 26987296 Paper 26965188 Paper 26929451 Paper 26929373 Paper 26837467 Paper 26816384 Paper 26780180 Paper 26764600 Paper 26764599 Paper 26649827 Paper 26350966 Paper 26343579 Paper 26195741 Paper 26170139 Paper 26098576

Abstract

The autophagy machinery has been shown to mediate host responses against a variety of infectious agents. These responses include the lysosomal degradation of specific pathogens via canonical autophagy, as well interferon-y-dependent killing of other pathogens via non-degradative pathways. Developing small molecules that enhance autophagy (ATG) protein-dependent pathways may have the potential to yield therapeutics against a broad spectrum of organisms. The proposed project applies next-generation synthetic chemistry and high-throughput screening to discover novel enhancers of ATG-mediated defense to pathogen infection. The project includes both phenotypic and target-based screens to discover modulators of autophagy and ATG-dependent processes, which will be tested for their activity against a range of pathogens of interest to the NIAID. Compounds with broad activity will be characterized for their mechanisms-of-action and developed further through medicinal chemistry to yield therapeutic leads suitable for testing treatment strategies in animal studies.

View original record on NIH RePORTER →