# Complex Cell Behaviors During Epithelial Homeostasis and Stress

> **NIH NIH R35** · UNIVERSITY OF WASHINGTON · 2024 · $166,758

## Abstract

Project Summary
Maintaining epithelial homeostasis is crucial for organismal health since its disruption is linked to multiple
human diseases, such as cancers. Cells elicit many behaviors to maintain the structure and function of
epithelia during normal homeostasis and stress. Comprehending their behavior is essential for promoting our
knowledge of how to keep epithelia healthy. We propose to take advantage of the robustness of the Drosophila
intestinal system to gain new insights into complex cell behaviors that remain understudied. Our R35-funded
research concerns ‘cell extrusion’, a process that removes unnecessary, defective, or potentially harmful cells
from epithelia without disrupting its barrier function. Over the past five years, we established the Drosophila
intestine as a new model for studying how intestinal epithelial cells expressing an oncogenic Ras (RasV12) are
eliminated apically and basally from the intestinal epithelium. We have identified multiple new players in the
process and provided new concepts to the field. Moreover, our study resulted in two new observations: 1)
Drosophila macrophage-like immune cells hemocytes infiltrate into the intestinal epithelium and elicit complex
cell behaviors under stress, and 2) intestinal epithelial cells generate long-range projections, resembling
‘airinimes’—structures that mediate long-distance signaling during pigment development in zebrafish. These
cell behaviors are documented in multiple model systems; however, their physiological significance and
underlying molecular mechanisms require additional investigation. Our observations bring an exciting
opportunity to leverage the powerful genetic tools available in Drosophila to understand the roles of these cell
behaviors in a native context and identify new players in these processes. Thus, we propose to expand our
research scope to include these additional complex cell behaviors. Continuing our work on cell extrusion, we
will focus on addressing what drives the elimination of RasV12-expressing intestinal epithelial cells from the
intestine. Regarding the behavior of hemocytes, we propose to investigate how hemocyte-mediated cell
behaviors contribute to the maintenance of the intestinal epithelium structure and function during normal
homeostasis and under stress. Lastly, we will study what signaling is mediated by the long-range projections
and what roles they play in the maintenance of intestinal epithelium. The overarching goal is to increase our
general understanding of complex cell behaviors underlying epithelial homeostasis by elucidating their
biological significance and discovering their molecular mechanisms. These proposed studies will help us to
learn the principles that keep epithelia healthy and prevent diseases associated with abnormalities in epithelial
homeostasis.

## Key facts

- **NIH application ID:** 11102302
- **Project number:** 3R35GM128752-06S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Young Kwon
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $166,758
- **Award type:** 3
- **Project period:** 2018-08-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11102302

## Citation

> US National Institutes of Health, RePORTER application 11102302, Complex Cell Behaviors During Epithelial Homeostasis and Stress (3R35GM128752-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11102302. Licensed CC0.

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