Thursday, March 19, 2026 3/19/2026

Genomic Research Capacity Building for Cryptococcal Meningitis

Award Number: R01NS118538
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2030

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Genomic Research Capacity Building for Cryptococcal Meningitis - Summary Cryptococcal meningitis (CM) is among the leading causes of death in AIDS-related opportunistic infections and causes 15% of AIDS-related mortality globally. In Uganda, CM accounts for 60% of adult meningitis in hospitalized patients. Even with treatment, the current mortality rate for CM is 65%, with surviving patients often exhibiting neurological impairment. This poor survival is due to a complex interaction between 1) failure to control fungal replication and 2) deleterious host immune response. To reduce CM deaths, we must simultaneously mitigate Cryptococcus virulence while rebalancing detrimental host responses towards protective immunity. The long-term objective of our research team is to identify novel treatment strategies for CM that reduce morbidity and mortality associated with this devastating disease. Our Virginia Tech, Mbarara University of Science and Technology, and Infectious Diseases Institute / Makerere University research team has collaborated on CM clinical studies since 2009. While similar clinical infrastructures are now present throughout Africa, there is still limited ability to perform associated basic and translational research related to CM. Thus, we will continue to build the infrastructure, knowledge base, and human capacity among African investigators to perform basic research in genomics and immunology that is translatable to clinical practice. In the last funding cycle, our research group made two key discoveries that influence patient mortality with CM: a) An immune signature for hypervirulence that is associated with high IFNγ production, and b) our genome-wide association studies (GWAS) identified genes associated with patients mortality as well as the IFNγ-mediated immune response. Thus, the scientific objective for this proposal is to define the impact of these Cryptococcus biomarkers on mortality, neurological deficits, and the immune response, and develop a subset of the biomarkers for clinical use. Three specific aims will accomplish this goal. In the first aim, we will use a bioinformatic approach to identify hypervirulent isolates in a collection of 500 Cryptococcus isolates. We will then analyze associations between the hypervirulent phenotype and patient immune responses in the second aim. In the third aim, we will develop the fungal genetic biomarkers for use in clinical practice as the first step towards development of a diagnostic bioassay. Taken together, these translational studies will define the molecular processes underlying CM and translate this information (i.e. biomarkers) into novel clinical assays to identify high-risk individuals for acute mortality or neurological impairment who would benefit from tailored medical care.


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: 2026 ( Subtotal = $643,278 )
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	2/24/2026	COMPETING CONTINUATION	$368,800
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	3/9/2026	COMPETING CONTINUATION	$0
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	3/6/2026	SUPPLEMENT FOR EXPANSION	$122,478
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	3/5/2026	SUPPLEMENT FOR EXPANSION	$152,000
														Subtotal = $643,278

Issue Date FY: 2024 ( Subtotal = $552,587 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/29/2024	NON-COMPETING CONTINUATION	$552,587
														Subtotal = $552,587

Issue Date FY: 2023 ( Subtotal = $552,587 )
2023	2023	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/1/2023	NON-COMPETING CONTINUATION	$552,587
														Subtotal = $552,587

Issue Date FY: 2022 ( Subtotal = $552,587 )
2022	2022	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/27/2022	NON-COMPETING CONTINUATION	$552,587
														Subtotal = $552,587

Issue Date FY: 2021 ( Subtotal = $526,621 )
2021	2021	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/30/2021	NON-COMPETING CONTINUATION	$526,621
														Subtotal = $526,621

Issue Date FY: 2020 ( Subtotal = $563,218 )
2020	2020	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE # 224	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/6/2020	NEW	$563,218
														Subtotal = $563,218

Grand Total All Awards = $3,390,878

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Genomic Research Capacity Building for Cryptococcal Meningitis

Award Number: R01NS118538

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2030

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