# Organ-scale regulation of stem cell dynamics

> **NIH NIH R35** · STANFORD UNIVERSITY · 2022 · $393,500

## Abstract

PROJECT SUMMARY
 Adult stem cells are the agents of organ renewal, remodeling and repair. Their hallmark ability to
concomitantly self-renew and produce terminal progeny enables lifelong maintenance of organ form and
function. At any given point in time, stem cells receive an ever-changing panoply of local and systemic signals
that reinforce stemness, activate division, or direct cellular fate as needed to respond to the tissue’s evolving
needs. These signals are deployed across space and time to marshal diverse stem cell behaviors for
coordinated, organ-scale outputs such as tissue homeostasis. Such emergent properties are fundamental to
the biology of adult tissues and essential for human health—yet, our grasp of their workings is rudimentary.
 My lab seeks to uncover the cellular mechanisms that underlie the robustness and flexibility of adult organ
maintenance. The goal of our MIRA program is to build a comprehensive framework for understanding how
each individual cell is guided by local and systemic signals for a net result of cellular equilibrium at the organ
scale. Our model system is the adult Drosophila midgut, a stem cell-based, tubular epithelial organ that is
functionally equivalent to the vertebrate stomach and small intestine. Our approach leverages unique live
imaging capabilities—pioneered in our lab—and precision genetic tools to illuminate real-time cell dynamics in
vivo and to probe the mechanisms that tune these dynamics.
 Here, we focus on three questions with broad significance to stem cell-based epithelial organs: 1) How
does the spatial distribution of stem cells––which we find is non-random, due to autonomous stem cell motility–
–impact the efficiency and robustness of organ turnover? 2) What are the real-time spatial kinetics of the EGF
feedback signals that equilibrate stem cell divisions and differentiated cell death, and does ectopic
manipulation of these kinetics support or negate a point-source model for organ size control? 3) How do new,
differentiating cells, which are born outside of the epithelium’s sealed network of occluding junctions, integrate
seamlessly into the organ as they differentiate?
 These studies build upon and expand our R01-funded work on organ-scale stem cell dynamics. Since the
cellular life cycle is a universal feature of self-renewing organs, the tunable, population-level mechanisms that
we uncover in the Drosophila midgut will provide a template for thinking about more complex organs, including
those in humans.

## Key facts

- **NIH application ID:** 10399573
- **Project number:** 5R35GM141885-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lucy Erin O'Brien
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,500
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399573

## Citation

> US National Institutes of Health, RePORTER application 10399573, Organ-scale regulation of stem cell dynamics (5R35GM141885-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10399573. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*