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CRITICAL ROLE OF THE ASC/CASPASE-1 PATHWAY IN TICK-BORNE RICKETTSIOSES

Award Number: K01CK000101
ORGANIZATION: NATIONAL CENTER FOR ZOONOTIC, VECTOR-BORNE, AND ENTERIC DISEASES
OPDIV: CDC
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/30/2007
PERIOD OF PERFORMANCE END DATE: 08/31/2011

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CRITICAL ROLE OF THE ASC/CASPASE-1 PATHWAY IN TICK-BORNE RICKETTSIOSES - DESCRIPTION (provided by applicant): This proposal describes a three year supervised career development program in Public Health research. Joap Pedra, Ph.D. completed his doctoral program in Medical Entomology at Purdue University and is currently a "Brown-Coxe Fellow of Medicine" at Yale University expanding his scientific skills in the field of immunobiology. Dr. Pedra is committed towards becoming an independent investigator in the field of tick-borne rickettsioses. Tick-borne rickettsioses are directly relevant to the health protection goals defined by the Centers for Disease Control and Prevention. Tick-borne rickettsial pathogens not only have the potential to affect the health of all segments of the population, but also can be used as biological weapons in case of a terrorist attack. Dr. Fikrig will mentor the scientific development of Dr. Pedra. Dr. Fikrig is a Professor of Medicine, Microbial Pathogenesis and Public Health at Yale University and a recognized leader in the field of tick-borne diseases. The research will focus on the mechanisms of immunity against Anaplasma phagocytophilum and Rickettsia conorii, two pathogens from the tick-borne rickettsial group. The mechanisms of immunity against A. phagocytophilum and R. conorii are largely unknown. Preliminary results shown by Dr. Pedra have demonstrated that Nod-like receptors play a critical role against A. phagocytophilum infection. Nod-like receptors recognize intracellular pathogens and trigger the cytokines IL-1b and IL-18 through their effect on the protease caspase-1. The research proposal described in this application aims to (1) examine the exact mechanism that triggers caspase-1 activation upon A. phagocytophilum infection; (2) assess the role of caspase-1/IL-18 in the adaptive immune response against A. phagocytophilum; and (3) identify the Nod-like receptor that triggers caspase-1 activation upon R. conorii infection. To accomplish these goals, Dr. Pedra will have free access to the modern facilities present at Yale University and will make use of the most current techniques available in immunobiology, microbial pathogenesis and proteomics.


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 = $0 )
2010	2009	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Innovations in Applied Public Health Research	001	3	7/20/2010	SUPPLEMENT FOR EXPANSION	$0
2010	2008	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Innovations in Applied Public Health Research	000	3	7/19/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $150,000 )
2009	2009	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Innovations in Applied Public Health Research	005	3	9/23/2009	SUPPLEMENT FOR EXPANSION	$150,000
2009	2008	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Innovations in Applied Public Health Research	001	2	9/2/2009	NON-COMPETING CONTINUATION	$0
2009	2008	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Innovations in Applied Public Health Research	000	2	2/11/2009	NON-COMPETING CONTINUATION	$0
2009	2008	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Innovations in Applied Public Health Research	002	2	9/23/2009	NON-COMPETING CONTINUATION	-$10,000
2009	2008	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Innovations in Applied Public Health Research	003	3	9/2/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$10,000
2009	2008	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Innovations in Applied Public Health Research	004	3	9/30/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $150,000

Issue Date FY: 2008 ( Subtotal = $150,000 )
2008	2008	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Innovations in Applied Public Health Research	000	2	9/6/2008	NON-COMPETING CONTINUATION	$150,000
														Subtotal = $150,000

Issue Date FY: 2007 ( Subtotal = $150,000 )
2007	2007	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Innovations in Applied Public Health Research	000	1	9/13/2007	NEW	$150,000
														Subtotal = $150,000

Grand Total All Awards = $450,000

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CRITICAL ROLE OF THE ASC/CASPASE-1 PATHWAY IN TICK-BORNE RICKETTSIOSES

Award Number: K01CK000101

ORGANIZATION: NATIONAL CENTER FOR ZOONOTIC, VECTOR-BORNE, AND ENTERIC DISEASES

OPDIV: CDC

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/30/2007

PERIOD OF PERFORMANCE END DATE: 08/31/2011

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