# Molecular mechanisms that regulate target cell sensitivity to Hedgehog morphogens

> **NIH NIH R00** · UNIVERSITY OF WASHINGTON · 2024 · $57,849

## Abstract

PROJECT SUMMARY/ABSTRACT
This is a proposal for a Diversity Supplement to fund research training and career development for Dorothy
Lartey, a talented undergraduate student and soon postbaccalaureate researcher in the Kong Lab at the
University of Washington. The parent grant for this proposal is 4R00GM132518-03, which focuses on
understanding the mechanisms that modulate a cell’s sensitivity to morphogens. Dorothy’s research involves
understanding the function of MOSMO, a ciliary tetraspan that establishes a cell’s sensitivity to the morphogen
Sonic Hedgehog (SHH). While we know that MOSMO forms a complex with MEGF8 (a single-pass
transmembrane protein) and MGRN1 (an E3 ubiquitin ligase) to regulate Smoothened (SMO, a core
transducer of the Hedgehog signaling pathway), its role in this process remains unresolved. To address this,
Dorothy will specifically examine the MOSMO/MEGF8 interaction and its ciliary localization, assessing both
their roles in regulating Hedgehog signaling activity. Aim 1 focuses on dissecting the MOSMO/MEGF8
interaction, using predictive models to disrupt the interaction and study subsequent effects on the localization
of SMO and Hedgehog signaling. Aim 2 focuses on MOSMO localization, generating constructs that do not
localize to the cilia and utilizing these to understand its role in regulating SMO. Lastly, Aim 3 examines the role
of cholesterol in regulating the activity of MOSMO. These proposed studies will advance our understanding of
how the MOSMO/MEGF8/MGRN1 (MMM) complex works and how target cells regulate their sensitivity to
extracellular cues. Through this project, Dorothy will learn many new technical skills to prepare her for
graduate school, including signaling assays and cell culture protocols. In addition, Dorothy will learn how to
organize her data and present her work as a poster at multiple meetings. Collectively, this supplement will
prepare Dorothy for success in biochemistry research in the form of graduate school and beyond.

## Key facts

- **NIH application ID:** 11047067
- **Project number:** 3R00GM132518-04S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jennifer Kong
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $57,849
- **Award type:** 3
- **Project period:** 2019-06-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047067

## Citation

> US National Institutes of Health, RePORTER application 11047067, Molecular mechanisms that regulate target cell sensitivity to Hedgehog morphogens (3R00GM132518-04S1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/11047067. Licensed CC0.

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