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Validation of a RSK-inhibitor as a Novel Therapeutic for

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI066612-01
Agency Tracking Number: AI066612
Amount: $435,093.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2005-2
Solicitation Year: 2005
Award Year: 2005
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
Luna Innovations, Inc. 2851 Commerce St
Blacksburg, VA 24060
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (434) 924-1152
Business Contact
Phone: (540) 552-5128
Research Institution

DESCRIPTION (provided by applicant): The inactivation of the host immune response by Yersinia, the causative agent of the plague, is mediated by a family of six proteins called Yersinia outer proteins, or Yops, namely YopE, YopH, YopO, YopM, YopJ, and YopT. While the mechanisms of action of YopE, YopH, YopO, YopJ, and YopT are fairly well understood, the effects of YopM on the host response to Yersinia infection remain largely uncharacterized. It is believed that YopM inhibits the secretion of cytokines from host cells, thereby preventing the recruitment of the host nonspecific immune response to sites of infection. However, recent studies have demonstrated the direct interaction of YopM with two intracellular targets, ribosomal S6 protein kinase 1 (RSK1) and protein kinase C-like 2 (PRK2). The association of RSK1 and PRK2 with YopM results in a novel complex that could potentially be responsible for inactivating the host immune response via a unique signaling pathway. The Luna Innovations/University of Virginia research team has discovered identified and characterized the only known specific inhibitor of RSK in vitro and in vivo. Using this inhibitor, SL0101, the Luna Innovations/University of Virginia research team propose to assess the feasibility of RSK as a YopM target during Yersinia infection, and SL0101 as a potential therapeutic agent to either prevent or reverse the effects of Yersinia infection on the host immune response. The focus of the Phase I program is to study the effects of SL0101 on the activity of the YopM/PRK2/RSK1 complex, and on cytokine production and secretion in macrophage cells infected with Yersinia. The recent identification of Yersinia strains resistant to multiple drugs, and its potential use as a biological warfare agent, mean that plague still poses a major threat to humans, and has been classified by the Center for Disease Control (CDC) as a Category A agent. Therefore, there exists an important need to identify novel methods of combating this threat to human health.

* Information listed above is at the time of submission. *

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