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Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis

Award Number: U01AI122275
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/21/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis - Project Summary Coccidioidomycosis (Valley Fever) is a serious public health problem for the Southwestern United States and all who visit there. A small proportion of infections result in progressive, debilitating, even life-threatening illness (disseminated coccidioidomycosis or DCM). All evidence suggests that this heightened susceptibility is due to differences in immunologic responses of the patient, clearly understood in overtly immunodeficient persons (i.e., those with AIDS) but not understood for the large majority of otherwise healthy patients with DCM. The NIAID intramural PI (Dr. Steven Holland) has identified inheritable gene mutations in a few patients each of which are associated with DCM. He has also found additional patients with DCM to have rare gene variants possibly producing deleterious consequences. These discoveries provide clues to the pathways that might be deregulated in other patients with DCM but who do not have such readily identifiable genetic alternations. This project builds on the ongoing collaboration between Dr. Holland and Dr. John Galgiani, University of Arizona (UA) Director of the Valley Fever Center for Excellence, to maintain a referral path for subjects living in Arizona to the existing program at the NIH Clinical Center. This work will better define the functional consequences of the Mendelian mutations that Dr. Holland has identified and how those differences permit DCM to occur. A second aim is to analyze gene expression of peripheral blood mononuclear cells of patients with DCM not associated with Mendelian mutations in comparison to persons who control coccidioidal infection without becoming ill. Such comparisons may identify dysregulated patterns of response and suggest which putatively deleterious variants in such patients might be responsible. A third aim is to genetically introduce Mendelian mutations associated with human DCM (such as one found by Dr. Holland in STAT4) into a mouse strain normally resistant to coccidioidal dissemination to determine if such mutations result in increased DCM. If so, we can also discover whether it is possible to prevent DCM in the transfected mice by immunization. The murine studies will use containment facilities available at the UA and not currently available at the NIH. As a result of this work, it may be possible to identify persons who, if infected, will develop DCM. Also, our findings may suggest new approaches to therapy or preventative vaccines.


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: 2023 ( Subtotal = -$1 )
2023	2020	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Allergy and Infectious Diseases Research	000	4	10/28/2022	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Allergy and Infectious Diseases Research	000	4	9/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $563,465 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Allergy and Infectious Diseases Research	000	4	2/20/2020	NON-COMPETING CONTINUATION	$563,465
														Subtotal = $563,465

Issue Date FY: 2019 ( Subtotal = $579,122 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Allergy and Infectious Diseases Research	000	3	3/1/2019	NON-COMPETING CONTINUATION	$579,122
														Subtotal = $579,122

Issue Date FY: 2018 ( Subtotal = $553,659 )
2018	2018	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Allergy and Infectious Diseases Research	000	2	1/30/2018	NON-COMPETING CONTINUATION	$553,659
														Subtotal = $553,659

Issue Date FY: 2017 ( Subtotal = $573,884 )
2017	2017	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Allergy and Infectious Diseases Research	000	1	3/20/2017	NEW	$573,884
														Subtotal = $573,884

Grand Total All Awards = $2,270,129

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Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis

Award Number: U01AI122275

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 03/21/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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