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Macrophage drug transport and metabolism in the outcome of antileishmania therapy

Award Number: R01AI104823
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/12/2013
PERIOD OF PERFORMANCE END DATE: 01/31/2019

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Macrophage drug transport and metabolism in the outcome of antileishmania therapy - DESCRIPTION (provided by applicant): There are no vaccines available to prevent leishmaniasis and vector management strategies are currently unsustainable. As a consequence, antileishmanial chemotherapy is the only control measure available. Despite this fact, there are high rates of treatment failure to first line drugs in Latin America (between 5 and 75%). Although failure is frequently interpreted as a consequence of parasite drug resistance, the therapeutic response is multifactorial, and evidence supports a central role of host factors in treatment outcome. However, the underlying pharmacological, immunological and metabolic events, the associated regulatory mechanisms, and their variation among individuals are unknown. To optimize the usefulness of available chemotherapy for cutaneous leishmaniasis caused by Leishmania Viannia, this project seeks to identify host biomarkers associated with successful or failed treatment outcomes. We will use a comprehensive experimental design integrating targeted, hypothesis-driven methodological approaches including pharmacogenomic signatures of treatment failure, and state-of-the-art unbiased methodologies for biomarker discovery and functional validation host genes involved in host cell drug-responsiveness (metabolic profiling and shRNA library screening). This project specifically aims to identify pharmacological correlates of the therapeutic outcome. Results from this project will generate critical understanding of host-pathogen interactions in the context of antileishmanial chemotherapy and variations that occur within individuals, will inform on the mechanisms of drug responsiveness of host cells to antileishmanial drugs, and will allow the identification of biomarkers of treatment response. This investigation will challenge current approaches for the treatment of leishmaniasis by providing pre-clinical information of the usefulness of multi-marker biosignatures as predictive and/or prognostic tools of therapeutic outcome. It will also drive the development of innovative combination therapies that target intracellular drug bioavailability. Integration of these findings will provide the bases for improved disease management and control, based on early predictions of treatment response and optimized therapeutic interventions.


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: 2019 ( Subtotal = $0 )
2019	2017	CORPORACION CENTRO INTERNACIONAL DE ENTRENAMIENTO E INVESTIGACIONES MEDICAS	CARRERA 125 NO. 19-2225	CALI	VALLE			COL	Allergy and Infectious Diseases Research	000	5	5/31/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	CORPORACION CENTRO INTERNACIONAL DE ENTRENAMIENTO E INVESTIGACIONES MEDICAS	CARRERA 125 NO. 19-2225	CALI	VALLE			COL	Allergy and Infectious Diseases Research	000	5	3/8/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $134,340 )
2017	2017	CORPORACION CENTRO INTERNACIONAL DE ENTRENAMIENTO E INVESTIGACIONES MEDICAS	CARRERA 125 NO. 19-2225	CALI	VALLE			COL	Allergy and Infectious Diseases Research	000	5	1/10/2017	NON-COMPETING CONTINUATION	$134,340
														Subtotal = $134,340

Issue Date FY: 2016 ( Subtotal = $134,699 )
2016	2016	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	000	4	12/21/2015	NON-COMPETING CONTINUATION	$134,699
														Subtotal = $134,699

Issue Date FY: 2015 ( Subtotal = $134,828 )
2015	2015	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	000	3	1/26/2015	NON-COMPETING CONTINUATION	$134,828
														Subtotal = $134,828

Issue Date FY: 2014 ( Subtotal = $134,877 )
2014	2014	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	000	2	3/7/2014	NON-COMPETING CONTINUATION	$134,877
														Subtotal = $134,877

Issue Date FY: 2013 ( Subtotal = $134,832 )
2013	2013	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	002	1	6/25/2013	NEW	-$134,832
2013	2013	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	001	1	6/5/2013	NEW	$13,484
2013	2013	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	004	1	6/28/2013	NEW	$121,348
2013	2013	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	000	1	2/11/2013	NEW	$121,348
2013	2013	CORPORACION CTR INTL DE ENTRENAMIENTO DE INVESTIGACION	CARRERA 125 NO. 19-225	CALI, VALLE				COL	Allergy and Infectious Diseases Research	003	1	6/28/2013	NEW	$13,484
														Subtotal = $134,832

Grand Total All Awards = $673,576

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Macrophage drug transport and metabolism in the outcome of antileishmania therapy

Award Number: R01AI104823

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/12/2013

PERIOD OF PERFORMANCE END DATE: 01/31/2019

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