# Novel pathways in C9ORF72-associated ALS and dementia

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $198,604

## Abstract

Project Summary/Abstract
 This is an application for the Mentored Clinical Scientist Career Development Award (K08) for
Dr. Daniel Mordes, an Instructor at Massachusetts General Hospital, Harvard Medical School. This
proposal describes a 5-year training program comprised of mentored laboratory research, formal
coursework, seminars, and conferences to foster the career development of an academic physician-scientist
in the subspecialty of neuropathology. This award will provide the necessary support to establish Dr.
Mordes as an independent investigator studying frontotemporal dementia (FTD) and amyotrophic lateral
sclerosis (ALS). He aims to 1) master current methods using stem cells to model neurological disease, 2)
obtain the executive skills to manage an independent translational research laboratory 3) become an expert
in the neuropathology of neurodegenerative disease. In order to accomplish these goals, Dr. Mordes has
designed a career development plan and assembled a group of accomplished basic scientists and physician-
scientists with expertise in stem cell biology, cellular signaling pathways, neurobiology, genome editing,
and neurodegenerative disease. The Applicant: Dr. Mordes graduated AOA from the MD/PhD program at
Vanderbilt University and has completed clinical training in Neuropathology at Massachusetts General
Hospital (MGH). Institutional Environment and Mentor: The training program combines the unique clinical
and research resources of MGH with the laboratory of Professor Kevin Eggan, who has a strong track record
of mentoring successful independent investigators, at Harvard University. Career Development Plan: Dr.
Mordes has assembled a team of senior faculty advisors at MGH and Harvard Medical School to support
his career development. His training will include the completion of advanced coursework and technical
training at Harvard, HMS, and the Broad Institute, and the presentation of his research at national meetings.
Research: Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by
severe cognitive impairments and the progressive loss of cortical neurons. There are no disease-modifying
treatments approved for FTD. Forms of FTD have shared neuropathological features with amyotrophic
lateral sclerosis (ALS), which is a rapidly progressive neuromuscular disorder. The most common genetic
cause of ALS and FTD is a hexanucleotide repeat expansion in C9ORF72, which is associated with the
production of toxic dipeptide repeat proteins (DPRs). Dr. Mordes has employed new methods of producing
human neurons from pluripotent stem cells to establish models of C9ORF72-associated disease. He aims
to understand the effects of DPRs in specific neuronal types through a combination of transcriptomics,
proteomics, and neuropathological approaches, and to identify novel cellular pathways for the development
of candidate treatments. Furthermore, he will determine the effects of a specific nuclear signaling pathway
...

## Key facts

- **NIH application ID:** 9993564
- **Project number:** 5K08NS104270-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Daniel Adam Mordes
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,604
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993564

## Citation

> US National Institutes of Health, RePORTER application 9993564, Novel pathways in C9ORF72-associated ALS and dementia (5K08NS104270-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993564. Licensed CC0.

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