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An extracellular vesicle component as a candidate to control cryptococcosis.

Award Number: R01AI183314
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: 03/21/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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An extracellular vesicle component as a candidate to control cryptococcosis. - An extracellular vesicle component as a candidate to control cryptococcosis. SUMMARY Fungal diseases are a major threat to immunocompromised patients. Cryptococcosis, caused by members of the Cryptococcus genus, is responsible for nearly 200,000 deaths worldwide annually. Immunocompromised individuals are the primary population that develop cryptococcal meningoencephalitis, a 100% fatal condition if left untreated. C. neoformans, the most common causative agent of cryptococcosis, has recently been classified as a critical threat by the World Health Organization. Despite their devastating impact on human health, fungal diseases have been consistently neglected, as demonstrated by the lack of available antifungal vaccines and our limited antifungal armamentarium. The Rodrigues and Nosanchuk laboratories have collaborated actively for over 15 years in the field of fungal infections and have extensively characterized fungal extracellular vesicles (EVs) in various models. EVs play crucial roles in fungal physiology and pathogenesis. Recently, we discovered that the tripeptide isoleucine-proline-isoleucine (IPI), a small molecule component of EVs, effectively controls cryptococcal infection in an invertebrate host. IPI acts as an inhibitor of dipeptidyl peptidase 4 (DPP4), which plays a role in fungal pathogenesis, as well as in host physiology, by regulating insulin and glucose. In this proposal, we aim to investigate the participation of IPI and DPP4 in fungal immunopathogenesis through three specific aims. Aim 1 will explore the protective mechanisms of IPI in animal models of cryptococcosis. Aim 2 focuses on understanding the roles of fungal and host DPP4 in disease progression, including their impact on glucose metabolism and the immune response. Aim 3 seeks to determine the relevance of IPI and DPP4 in other fungal models. Successful completion of this project will provide a comprehensive characterization of a novel candidate for combating cryptococcosis and perhaps other diseases. Furthermore, we anticipate gaining insights into the connection between DPP4 and fungal pathogenesis. This proposal aims to foster intercontinental collaboration and enhance the capabilities of Fiocruz, the Brazilian institution leading this collaborative effort.


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 = $134,240 )
2026	2026	FUNDACAO OSWALDO CRUZ	AVENIDA BRASIL 4365 QUININO, SALA 303	RIO DE JANEIRO				BRA	Allergy and Infectious Diseases Research	000	3	2/18/2026	NON-COMPETING CONTINUATION	$134,240
														Subtotal = $134,240

Issue Date FY: 2025 ( Subtotal = $130,212 )
2025	2025	FUNDACAO OSWALDO CRUZ	AVENIDA BRASIL 4365 QUININO, SALA 303	RIO DE JANEIRO				BRA	Allergy and Infectious Diseases Research	000	2	1/13/2025	NON-COMPETING CONTINUATION	$130,212
														Subtotal = $130,212

Issue Date FY: 2024 ( Subtotal = $115,880 )
2024	2024	FUNDACAO OSWALDO CRUZ	AVENIDA BRASIL 4365 QUININO, SALA 303	RIO DE JANEIRO				BRA	Allergy and Infectious Diseases Research	002	1	6/25/2024	NEW	$115,880
2024	2024	FUNDACAO OSWALDO CRUZ	AVENIDA BRASIL 4365 QUININO, SALA 303	RIO DE JANEIRO				BRA	Allergy and Infectious Diseases Research	000	1	3/21/2024	NEW	$115,880
2024	2024	FUNDACAO OSWALDO CRUZ	AVENIDA BRASIL 4365 QUININO, SALA 303	RIO DE JANEIRO				BRA	Allergy and Infectious Diseases Research	001	1	6/18/2024	NEW	-$115,880
														Subtotal = $115,880

Grand Total All Awards = $380,332

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An extracellular vesicle component as a candidate to control cryptococcosis.

Award Number: R01AI183314

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: 03/21/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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