# Deciphering the role of MEMO1 during amelogenesis

> **NIH NIH F31** · UNIVERSITY OF IOWA · 2024 · $37,973

## Abstract

PROJECT SUMMARY: Amelogenesis imperfecta (AI) is a rare genetic congenital enamel disorder
characterized by enamel that is prone to rapid wear and breakage. AI affects approximately 1 in 15,000
children in the United States and poses a significant financial and psychosocial burden for those affected.
Moreover, our understanding of the etiology of AI is limited with roughly 50% of cases having no known genetic
cause. The long-term goal of this research proposal is to study the function of a novel AI associated gene,
Mediator of Cell Motility 1, or MEMO1, to uncover molecular mechanisms of normal and abnormal enamel
development—ultimately leveraging these details in regenerating enamel. The applicant previously identified a
role for the protein MEMO1 during amelogenesis. Oral ectoderm loss of MEMO1 led to severe enamel
hypomineralization and chipping, like that observed in humans afflicted with AI. Despite severe enamel
pathology associated with loss of Memo1, several questions remained. For example, what are the spatial and
temporal dynamics of MEMO1 during amelogenesis? How does MEMO1 function within the ameloblast? This
fellowship aims to tackle these questions with the central hypothesis that MEMO1 is essential within the
definitive ameloblast at the earliest onset of enamel mineralization and functions within a network of integrin-
based signaling and cytoskeletal dynamics. This hypothesis is based on preliminary data and shared enamel
pathology associated with oral epithelial loss of Memo1 and integrins. Two experimental aims will address this
central hypothesis. In aim 1, conditional mouse genetics, µCT, nano-indentation, histology,
immunofluorescence, and single cell RNA sequencing will assess the spatial and temporal requirements of
MEMO1 during amelogenesis. In aim 2, a Memo1 knockout ameloblast cell line will be coupled with
immunofluorescence, integrin-activation assays, live-cell imaging, co-immunoprecipitation, proximity-based
ligation proteomics, and pull-down assays to assess MEMO1’s ameloblast-specific, cellular function. Insights
from the proposed research will enhance our comprehension of MEMO1’s contribution to normal enamel
development and mechanisms underlying AI. The resulting insights may pave the way for improved diagnostic
and therapeutic strategies for AI. With combined mentorship from Dr. Van Otterloo and Dr. Tootle, the
applicant will develop skillsets in single cell bioinformatic analysis, proteomics, live cell imaging, and micro-
computed tomography greatly advancing their doctoral training. The comprehensive training plan, cohesive
team, and supportive institutional environment outlined in this research proposal will advance treatment of oral
and dental disorders and propel the applicant forward along a path of an independent researcher.

## Key facts

- **NIH application ID:** 11068217
- **Project number:** 1F31DE034609-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Samantha Wuebker
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $37,973
- **Award type:** 1
- **Project period:** 2024-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11068217

## Citation

> US National Institutes of Health, RePORTER application 11068217, Deciphering the role of MEMO1 during amelogenesis (1F31DE034609-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/11068217. Licensed CC0.

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