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Task Last Updated: 01/21/2009 
Division Name: Human Research 
Program/Discipline: NSBRI 
Element/Subdiscipline: Radiation Effects Team 
Project Title: The Role of Intestinal Inflammation in Acute Effects Induced by Exposure to Protons During Solar Particle Events 
Joint Agency Name:  
PI Name: Trani, Daniela   PI Phone: 202-687-5216  
PI Email: dt232@georgetown.edu  Fax: 202-687-3140 
PI Organization Type: UNIVERSITY 
Organization Name: Georgetown University 
PI Address 1: 3970 Reservoir Rd, NW 
PI Address 2: Research Building E504/508 
PI Web Page:  
City: Washington State: DC Zip Code: 20057 Congressional District: 1
Comments:  
Project Type: GROUND  Solicitation: NSBRI-RFA-08-03 
Start Date: 11/01/2008  End Date: 10/31/2010 
Fiscal Year: 2009     
No. of Post Docs:   No. of PhD Degrees:  
No. of PhD Candidates:   No. of Master' Degrees:  
No. of Master's Candidates:   No. of Bachelor's Degrees:  
No. of Bachelor's Candidates:   Monitoring Center: NSBRI 
Contact Monitor:   Contact Phone:  
Contact Email:      
Flight Program:  
Flight Assignment:

 
Key Personnel Changes/Previous PI:  
COI Name: COI Institution:
Grant/Contract No.: NCC 9-58-PF01904 
Performance Goal No.:  
Performance Goal Text:

 
Task Description:  POSTDOCTORAL FELLOWSHIP.

Sporadic and unpredictably large solar particle events may occur several times during the 11-year solar cycle and pose serious health risks for manned exploratory missions beyond low Earth orbit. Also, it acutely could cause the prodromal syndrome, a transient period of anorexia, nausea and vomiting that starts within a few hours and may compromise crew performance. At expected doses, acute effects could be due to direct damage to intestinal mucosa as well as the effect of injury responses that involve intercellular signaling.

Ionizing radiation (IR) activates a complex network of stress responses that affect cellular functions and cellular viability and triggers altered expression of a variety of cytokines and other intercellular messengers. Many of these signaling events can impinge on processes associated with inflammatory responses. Many studies show a general over expression of pro-inflammatory markers systemically and in tissues such as intestine after IR.

A major mediator of inflammatory signaling is p38 MAP kinase (p38). It is upstream, and sometimes downstream, of key cytokines including TNFalpha, IL-6, and IL-1, as well as other key mediators like COX2 and p53. In the case of the prodromal syndrome, inflammatory signaling may impact intestinal function either directly by damage to the mucosa, by local production of inflammatory cytokines, or by systemic effects of inflammatory cytokines on the gut.

My principal hypothesis is that inflammatory signaling contributes to the prodromal syndrome and can affect the gut either by local signaling events and/or by systemic cytokine signaling. I will use a genetic approach in a defined mouse model system to study inflammatory signaling after space radiation with emphasis on protons and the effects of such signaling on cellular and molecular parameters in the intestine. By blocking p38 signaling with dominant-negative p38 mutant, we will be able to assess the potential advantages of anti-inflammatory therapy to treat the prodromal syndrome.

 
Research Impact/Earth Benefits: 0

Task Progress: New project for FY2009.

 
Bibliography Type: Description: (Last Updated: 12/10/2009)