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IN VIVO CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS

Award Number: R01HD020337
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/1985
PERIOD OF PERFORMANCE END DATE: 08/31/2011

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IN VIVO CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS - The proposed studies will investigate the mechanism of activation of Ca++/calmodulin-dependent protein kinase IV (CaM kinase IV) during hypoxia that leads to activation of cyclic AMP-response element binding (CREB) protein and triggers the transcription of apoptotic genes resulting in hypoxic neuronal death. We will test the hypothesis that the mechanism of increased activation of CaM kinase IV during hypoxia is due to tyrosine phosphorylation of calmodulin and tyrosine phosphorylation of CaM kinase IV by the tyrosine kinases, Src tyrosine kinase and epidermal growth factor receptor (EGFR) tyrosine kinase. We propose that cerebral hypoxia-induced increased tyrosine phosphorylation of calmodulin (at Tyr99) leads to increased affinity for its binding at the calmodulin binding domain of the CaM kinase IV enzyme and results in increased activation of CaM kinase IV. The increased tyrosine phosphorylation of CaM kinase IV (at Tyr154 and Tyr172) leading to modification of the active site domain of the enzyme leads to increased affinity for its substrate and results in increased activation of CaM kinase IV. Experimental protocols will be carried out on newborn piglets investigating: (1) the effect of hypoxia on Tyr99 phosphorylation of calmodulin, Tyr154 and Tyr172 phosphorylation of CaM kinase IV, and activity of CaM kinase IV in neuronal nuclei, (2) the effect of hypoxia on the activity of Src kinase and EGFR kinase, and tyrosine phosphorylation at the active site of Src kinase (Tyr416) and EGFR kinase (Tyr1173), an index of enzyme activation, using specific anti-Tyr416-p-Src kinase and anti-Tyr1173-p-EGFR kinase antibodies to demonstrate activation of Src and EGFR tyrosine kinases in the cerebral cortex of hypoxic piglets.


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 = $515,320 )
2010	2010	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Trans-NIH Recovery Act Research Support	000	26	8/23/2010	NON-COMPETING CONTINUATION	$515,320
														Subtotal = $515,320

Issue Date FY: 2009 ( Subtotal = $503,509 )
2009	2009	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Trans-NIH Recovery Act Research Support	001	25	8/28/2009	COMPETING CONTINUATION	$503,509
2009	2008	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	24	8/28/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $503,509

Issue Date FY: 2008 ( Subtotal = $429,846 )
2008	2008	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	24	12/11/2007	NON-COMPETING CONTINUATION	$429,846
														Subtotal = $429,846

Issue Date FY: 2007 ( Subtotal = $428,046 )
2007	2007	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	23	12/8/2006	NON-COMPETING CONTINUATION	$428,046
														Subtotal = $428,046

Issue Date FY: 2006 ( Subtotal = $429,282 )
2006	2006	DREXEL UNIVERSITY	3201 ARCH STREET, SUITE 100	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	22	11/25/2005	NON-COMPETING CONTINUATION	$429,282
														Subtotal = $429,282

Issue Date FY: 2005 ( Subtotal = $426,807 )
2005	2005	DREXEL UNIVERSITY	32ND & CHESTNUT STREETS	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	21	12/1/2004	NON-COMPETING CONTINUATION	$426,807
														Subtotal = $426,807

Issue Date FY: 2004 ( Subtotal = $414,375 )
2004	2004	DREXEL UNIVERSITY	32ND & CHESTNUT STREETS	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	20	12/31/2003	COMPETING CONTINUATION	$414,375
														Subtotal = $414,375

Issue Date FY: 2003 ( Subtotal = $336,010 )
2003	2003	MCP HAHNEMANN UNIVERSITY	1505 RACE STREET MAIL STOP 485	PHILADELPHIA	PA	19102	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	19		NON-COMPETING CONTINUATION	$336,010
														Subtotal = $336,010

Issue Date FY: 2002 ( Subtotal = $329,045 )
2002	2002	MCP HAHNEMANN UNIVERSITY	1505 RACE STREET MAIL STOP 485	PHILADELPHIA	PA	19102	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	18	11/28/2001	NON-COMPETING CONTINUATION	$329,045
														Subtotal = $329,045

Issue Date FY: 2001 ( Subtotal = $322,288 )
2001	2001	MCP HAHNEMANN UNIVERSITY	1505 RACE STREET MAIL STOP 485	PHILADELPHIA	PA	19102	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	17	12/27/2000	NON-COMPETING CONTINUATION	$322,288
														Subtotal = $322,288

Issue Date FY: 2000 ( Subtotal = $315,724 )
2000	2000	DREXEL UNIVERSITY COLLEGE OF MEDICINE	3201 ARCH STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Child Health and Human Development Extramural Research	000	16	3/17/2000	NON-COMPETING CONTINUATION	$315,724
														Subtotal = $315,724

Issue Date FY: 1999 ( Subtotal = $279,545 )
1999	1999	ALLEGHENY UNIV OF THE HLTH SCIENCES	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	15	11/25/1998	COMPETING CONTINUATION	$279,545
														Subtotal = $279,545

Issue Date FY: 1998 ( Subtotal = $255,989 )
1998	1998	ALLEGHENY UNIV OF THE HLTH SCIENCES	503 MARTINDALE STREET	PITTSBURGH	PA	15212	ALLEGHENY	USA	Child Health and Human Development Extramural Research	000	13	1/12/1998	NON-COMPETING CONTINUATION	$255,989
														Subtotal = $255,989

Grand Total All Awards = $4,985,786

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IN VIVO CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS

Award Number: R01HD020337

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/1985

PERIOD OF PERFORMANCE END DATE: 08/31/2011

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