# Mapping Brainstem Motor Neuron Subtypes and Genetic Pathways Involved in their Differential Susceptibility to Disease

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $155,622

## Abstract

PROJECT SUMMARY/ABSTRACT
 This NIH K08 proposal describes a five-year training program for career development in academic
neuropathology and developmental neurogenetics. Dr. Matthew Rose has completed clinical residency in
Anatomic Pathology and fellowship in Neuropathology at Brigham and Women’s Hospital (BWH) and Boston
Children’s Hospital (BCH) at Harvard Medical School (HMS), and will embark on a research program designed
to train for an independent academic career in neurologic disease-oriented research.
 In this training program, Dr. Rose will acquire in-depth experience in the study of ocular motor neuron (OMN)
development and axon targeting, interpretation of single cell RNA-sequencing, analysis of gene regulatory
networks, tissue clearing and advanced imaging approaches, and gene-editing technologies. His mentor, Dr.
Elizabeth Engle (a Professor of Neurology and HHMI Investigator at BCH), is a leader in brainstem OMN
development and congenital cranial dysinnervation disorders (CCDDs) that involve these motor neurons. Her
laboratory has extensive experience in human and mouse genetics, neuroanatomy, large data analyses,
molecular biology, imaging, and cell culture techniques. She has an established track record for mentoring other
trainees to successful careers in biomedical investigation. In addition to his mentor, he has assembled a group
of collaborators with complementary expertise in these disciplines, and an Advisory Committee of senior faculty
with extensive experience in guiding physician-scientists through the transition to independence. He will
supplement this training with didactics and presentation of work at national meetings.
 The primary scientific goal of the proposed research plan is to study normal and abnormal OMN specification
and axonal growth and guidance in health and disease. Dr. Rose provides an initial map of the genetic
differences among brainstem motor neurons that may serve as a foundation for further studies of all motor neuron
diseases. These preliminary data will be used as a foundation to further study the development of the OMN
subnuclei by discovering markers of each OMN subpopulation, and then applying those markers to the study of
the CCDDs. The central hypothesis of this proposal is that the differences in gene expression among OMN
subpopulations may predispose certain subtypes to undergo dysinnervation in different CCDDs.
 Single cell RNA-seq will be performed on the three primary OMNs: the oculomotor, trochlear, and abducens
brainstem nuclei, in order to discover markers of each subpopulation. In combination with ATAC-seq, the
transcriptional regulatory networks for OMN specification will be investigated. Unique markers of each OMN
subpopulation will then be used to study normal OMN axon projections to distinct muscle targets, as well as
using them to dissect the contributions of different populations to the stereotypic and pathologic aberrant
innervations observed in the CCDDs. These studies have s...

## Key facts

- **NIH application ID:** 10064032
- **Project number:** 5K08NS099502-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Matthew F Rose
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,622
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-09-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064032

## Citation

> US National Institutes of Health, RePORTER application 10064032, Mapping Brainstem Motor Neuron Subtypes and Genetic Pathways Involved in their Differential Susceptibility to Disease (5K08NS099502-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10064032. Licensed CC0.

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