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Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells

Award Number: R35GM125012
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells - ABSTRACT/ SUMMARY The Immuno-modulatory Biomaterials Laboratory at the University of Florida focuses on the development of novel biomaterial systems that can manipulate the immune system. Our goal is to design the next generation of immunotherapeutics for applications in immune-related diseases. This multidisciplinary work incorporates aspects of biomaterials engineering, drug delivery, immunology, biochemistry, and cell physiology. One of the main research programs in our lab is understanding controlled vomocytosis (non-lytic exocytosis) of fungal cells from phagocytes. Our primary motivation for elucidation of this process is the development of a hybrid fungal- microparticle system that can accomplish phagocytic cell-mediated delivery of drugs, including vaccines to guarded sites such as the brain and lymph nodes. Phagocytic cells (particularly macrophages [MΦ] and dendritic cells [DCs])) have evolved to circulate through peripheral tissue, engulf foreign particulate matter and traffick to specific tissues. Evidently, phagocytic cells can transport particulate materials from peripheral tissues to lymphatic organs. Typically, following phagocytosis, materials that have been engulfed are taken into the phagosome (vacuole in the cytoplasm of a cell containing a phagocytosed particles) where a degradative process occurs due to secretion of reactive oxygen species (ROS), acidic pH and digestive enzymes. This stage would be counterproductive to the integrity of the internalized material. Moreover, for delivery from a phagocyte there has to be expulsion, and there is precedent for such behavior. The fungal cell, Cryptococcus neoformans, elicits vomocytosis or (non-lytic exocytosis) from macrophages. There is still little understanding about the mechanisms governing this phenomena. Here, we seek to demystify vomocytosis - a phenomenon that is understudied. Ultimately, our long-term goal is to develop a universally-deployable, bug-microparticle platform as an effective therapeutic for a plethora of immune and neurological conditions. These goals can only be accomplished through comprehension of the interactions of this remarkable pathogen with innate immune cells. Critically, to address gaps in our knowledge requires (i) the ability to identify vomocytosis in vivo, (ii) cognizance of dissemination and interaction in hosts at the organ, tissue, cellular and subcellular levels and (iii) probing the role of Ca2+ in CN vomocytosis. This proposal seeks to systematically cover these next steps using state-of-the- art engineering tools, including those devised by the PI’s group. Therefore, the proposed program is highly relevant to the mission of the National Institute of General Medical Sciences (NIGMS), which pertains to supporting research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention.


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 = $402,782 )
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	8	3/10/2026	NON-COMPETING CONTINUATION	$40,278
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	8	1/15/2026	NON-COMPETING CONTINUATION	$362,504
														Subtotal = $402,782

Issue Date FY: 2025 ( Subtotal = $403,650 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	001	7	1/8/2025	NON-COMPETING CONTINUATION	$363,285
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	002	7	8/8/2025	NON-COMPETING CONTINUATION	$40,365
2025	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	000	6	11/22/2024	COMPETING CONTINUATION	$0
														Subtotal = $403,650

Issue Date FY: 2024 ( Subtotal = $399,769 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Biomedical Research and Research Training	002	6	3/25/2024	COMPETING CONTINUATION	$403,931
2024	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	5	3/19/2024	NON-COMPETING CONTINUATION	-$125
2024	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	12/6/2023	NON-COMPETING CONTINUATION	-$4,037
														Subtotal = $399,769

Issue Date FY: 2021 ( Subtotal = $378,106 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	5	7/28/2021	NON-COMPETING CONTINUATION	$378,106
														Subtotal = $378,106

Issue Date FY: 2020 ( Subtotal = $378,792 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	4	7/14/2020	NON-COMPETING CONTINUATION	$378,792
														Subtotal = $378,792

Issue Date FY: 2019 ( Subtotal = $438,247 )
2019	2019	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	001	3	7/18/2019	NON-COMPETING CONTINUATION	$379,444
2019	2019	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	2	6/24/2019	SUPPLEMENT FOR EXPANSION	$58,803
														Subtotal = $438,247

Issue Date FY: 2018 ( Subtotal = $380,065 )
2018	2018	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	2	7/5/2018	NON-COMPETING CONTINUATION	$380,065
														Subtotal = $380,065

Issue Date FY: 2017 ( Subtotal = $374,957 )
2017	2017	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Biomedical Research and Research Training	000	1	7/27/2017	NEW	$374,957
														Subtotal = $374,957

Grand Total All Awards = $3,156,368

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Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells

Award Number: R35GM125012

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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