Establishing Sts-1 as a Novel Target to Treat Deadly Pathogen Infections
Abstract
This proposal, in the Fiscal Year 2016 Peer Reviewed Medical Research Program Topic Area of Anti-Microbial Resistance, addresses a unique approach to improving clinical outcomes for individuals who have contracted life-threatening bacterial and fungal infections. The Sts proteins have been shown to regulate how cells of the immune system respond to extracellular cues. Experimental mice in which the Sts proteins are functionally inactivated have been shown to be profoundly resistant to infection with high doses of different microbial pathogens. The resistance of mutant mice is associated with an altered inflammatory response and significantly enhanced pathogen clearance. In an effort to enhance host immune responses during infection, we propose to establish Sts-1 as a biological target against which to develop inhibitory compounds. We will determine its druggability, lay the foundation for a high-throughput screening campaign to identify specific inhibitors, and evaluate lead compounds from an initial pilot screen. In addition, the regulatory role of Sts-1 in leukocyte functional responses will be determined. The major innovative aspect of this proposal lies in the potential for developing improved clinical strategies to fight deadly human pathogens. Success in the short term will establish the feasibility of improving the human anti-microbial immune response via pharmacological inhibition of an important immune regulator. Success in the long term will yield novel treatments that will significantly reduce the morbidity and mortality associated with a number of pathogenic microorganisms.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710147
Entities
People
- Nicholas Carpino
Organizations
- Stony Brook University
- United States Army