# Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2024 · $403,931

## Abstract

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.

## Key facts

- **NIH application ID:** 10842682
- **Project number:** 2R35GM125012-06
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Jamal S Lewis
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,931
- **Award type:** 2
- **Project period:** 2017-08-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842682

## Citation

> US National Institutes of Health, RePORTER application 10842682, Leveraging Engineering Approaches to understand Cryptococcal Vomocytosis from Immune Cells (2R35GM125012-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10842682. Licensed CC0.

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