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CYTOKINE SIGNALING NETWORK RESPONSE TO SMALLPOX VACCINE

Award Number: K25AI064625
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2006
PERIOD OF PERFORMANCE END DATE: 03/31/2011

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CYTOKINE SIGNALING NETWORK RESPONSE TO SMALLPOX VACCINE - DESCRIPTION (provided by applicant): The identification of the molecular and cellular basis for adverse events observed in patients immunized against smallpox is of great public health interest. This is especially true today given efforts to defend the U.S. population and military against potential bioterrorism agents. We have shown recently that adverse vents following smallpox vaccination correlate with systemic cytokine patterns, suggesting a role for cytokines in the pathogenesis of adverse events. A challenge to further delineating the immunological mechanisms of adverse events is that cytokines rarely act in isolation to induce an immune response, but rather they work in a complex network to which immune system cells respond. Cytokines are small signaling proteins that integrate the activities of immune system cells. While it is often well understood how they act individually, the behavior of cytokines as part of a signaling network is less well known and likely depends on the nature of the infecting organism. We propose to develop and evaluate a comprehensive strategy to identify detailed kinetic cytokine network models associated with adverse events following smallpox vaccination. This strategy will be developed and evaluated using proteomic time-series data available from 103 volunteers that are part of an ongoing NIAID/NIH-sponsored trial to evaluate the Aventis Pasteur Smallpox Vaccine (APSV). We will develop software tools using machine learning algorithms to automatically discover cytokine signaling network models from observed time-series cytokine expression levels. Once the underlying cytokine network model has been estimated, our goal is to use the dynamic model as a simulation tool to suggest ways to create vaccines that minimize the risk of adverse events associated with vaccination. The software tools developed in this proposal will be generally applicable for biomedical research to understand the biochemical interactions in time-series data, and, thus, a useful and novel software package will be made available to the vaccine research community. The experience and knowledge gained during the collaboration on this important research problem in immunology coupled with the didactic and mentoring portions of the training program will create a firm foundation upon which I can develop and test significant hypotheses for future studies on the immunology of infectious diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $113,137 )
2010	2010	UNIVERSITY OF TULSA	600 SOUTH COLLAGE	TULSA	OK	74104	TULSA	USA	Allergy and Infectious Diseases Research	002	7	4/5/2010	NON-COMPETING CONTINUATION	$113,132
2010	2009	UNIVERSITY OF TULSA	600 SOUTH COLLAGE	TULSA	OK	74104	TULSA	USA	Allergy and Infectious Diseases Research	000	6	1/6/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$39,676
2010	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	001	5	1/6/2010	NON-COMPETING CONTINUATION	-$39,671
														Subtotal = $113,137

Issue Date FY: 2009 ( Subtotal = $109,916 )
2009	2009	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	5	3/19/2009	NON-COMPETING CONTINUATION	$109,916
														Subtotal = $109,916

Issue Date FY: 2008 ( Subtotal = $106,794 )
2008	2008	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	4	4/9/2008	NON-COMPETING CONTINUATION	$106,794
														Subtotal = $106,794

Issue Date FY: 2007 ( Subtotal = $103,762 )
2007	2007	UNIVERSITY OF ALABAMA AT BIRMINGHAM	UAB STATION, CBB 990	BIRMINGHAM	AL	35294	JEFFERSON	USA	Allergy and Infectious Diseases Research	000	3	8/29/2007	NON-COMPETING CONTINUATION	$103,762
														Subtotal = $103,762

Issue Date FY: 2006 ( Subtotal = $100,818 )
2006	2006	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Allergy and Infectious Diseases Research	000	1	3/17/2006	NEW	$100,818
														Subtotal = $100,818

Grand Total All Awards = $534,427

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CYTOKINE SIGNALING NETWORK RESPONSE TO SMALLPOX VACCINE

Award Number: K25AI064625

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2006

PERIOD OF PERFORMANCE END DATE: 03/31/2011

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