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MEP pathway resistance in Plasmodium falciparum

Award Number: R01AI103280
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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MEP pathway resistance in Plasmodium falciparum - PROJECT SUMMARY Severe malaria due to infection by Plasmodium falciparum is a serious threat to global health with over a million deaths per year. New antimalarial agents are needed due to widespread resistance to existing therapies. A promising antimalarial drug target is the MEP pathway of isoprenoid biosynthesis, which is not found in humans. We have used forward genetic screening to identify malaria parasites resistant to MEP pathway inhibition. We have thus identified a new family of metabolic regulators in malaria, the HAD proteins. We now propose to determine the mechanism by which loss of HAD phosphatases confers drug resistance (Aim 1); establish the biological functions of HADs in parasite development (Aim 2); and use a new MEP pathway inhibitor to identify and characterize additional mechanisms of resistance (Aim 3). We will identify P. falciparum genes and pathways that genetically interact with the essential MEP pathway and our strong preliminary results support this approach. In addition, our results will inform our understanding of the basic biology of the HAD family of metabolic regulators and will determine whether HAD-mediated drug resistance can be transmitted.


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: 2025 ( Subtotal = $452,870 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	13	3/11/2025	NON-COMPETING CONTINUATION	$452,870
														Subtotal = $452,870

Issue Date FY: 2024 ( Subtotal = $452,490 )
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	12	3/14/2024	NON-COMPETING CONTINUATION	$452,490
2024	2022	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	10	9/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $452,490

Issue Date FY: 2023 ( Subtotal = $472,425 )
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	11	4/7/2023	COMPETING CONTINUATION	$472,425
2023	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	10	3/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $472,425

Issue Date FY: 2022 ( Subtotal = $423,000 )
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	10	12/1/2021	NON-COMPETING CONTINUATION	$423,000
														Subtotal = $423,000

Issue Date FY: 2021 ( Subtotal = $423,000 )
2021	2021	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	9	11/25/2020	NON-COMPETING CONTINUATION	$423,000
														Subtotal = $423,000

Issue Date FY: 2020 ( Subtotal = $423,000 )
2020	2020	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	8	11/19/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$423,000
2020	2020	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	003	8	1/28/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$164,240
2020	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	7	1/28/2020	NON-COMPETING CONTINUATION	-$164,240
2020	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	7	11/19/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $423,000

Issue Date FY: 2019 ( Subtotal = $370,125 )
2019	2019	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	7	11/23/2018	NON-COMPETING CONTINUATION	$370,125
														Subtotal = $370,125

Issue Date FY: 2018 ( Subtotal = $383,250 )
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	002	6	3/14/2018	COMPETING CONTINUATION	$334
2018	2018	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	6	11/15/2017	COMPETING CONTINUATION	$383,250
2018	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	001	5	3/14/2018	NON-COMPETING CONTINUATION	-$334
														Subtotal = $383,250

Issue Date FY: 2017 ( Subtotal = $342,000 )
2017	2017	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Allergy and Infectious Diseases Research	000	5	11/17/2016	NON-COMPETING CONTINUATION	$342,000
														Subtotal = $342,000

Issue Date FY: 2016 ( Subtotal = $342,000 )
2016	2016	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	4	11/20/2015	EXTENSION WITH OR WITHOUT FUNDS	$342,000
														Subtotal = $342,000

Issue Date FY: 2015 ( Subtotal = $342,000 )
2015	2015	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	3	11/14/2014	NON-COMPETING CONTINUATION	$342,000
														Subtotal = $342,000

Issue Date FY: 2014 ( Subtotal = $342,000 )
2014	2014	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	2	11/15/2013	NON-COMPETING CONTINUATION	$307,800
2014	2014	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	2	6/5/2014	NON-COMPETING CONTINUATION	$34,200
														Subtotal = $342,000

Issue Date FY: 2013 ( Subtotal = $315,614 )
2013	2013	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	003	1	7/25/2013	NEW	$0
2013	2013	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	002	1	5/30/2013	NEW	$13,430
2013	2013	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	11/21/2012	NEW	$302,184
2013	2013	WASHINGTON UNIVERSITY	CAMPUS BOX 1034	SAINT LOUIS	MO	63112	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	1	2/27/2013	NEW	$0
														Subtotal = $315,614

Grand Total All Awards = $5,083,774

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MEP pathway resistance in Plasmodium falciparum

Award Number: R01AI103280

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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