# Diversity Supplement: Single Cell Analyses of Neuroimmune Dysfunctions in the Thalamocortical Circuit in FTLD

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $93,282

## Abstract

Project Summary
Frontotemporal dementia (FTD) is an early onset neurodegenerative disease, and the second most common
cause of dementia in patients 60 years or younger. The majority of familial FTD are caused by intronic
hexanucleotide (CCCCGG) repeat expansion in chromosome 9 open reading frame 72 (C9orf72) gene and by
dominant mutations in the Progranulin (GRN) gene, which account for 25% and 15% of familial FTD cases,
respectively. These mutations cause haploinsufficiency in both genes and lead to abnormal protein aggregation
involving RNA binding protein TDP-43 in neuronal nuclei and cytoplasm. The goal of the parent grant (R01
AA027074-03) is to test the hypothesis that loss of PGRN disrupts neuroimmune interaction in the thalamo-
cortical circuit in Grn-/- mice. The purpose of this Diversity Supplement is to expand the scope of the parent
grant and characterize the potential interaction of C9orf72 and progranulin in neurodegeneration. To this end,
the proposed trainee, Naznin Jahan – a 4th year graduate student in the BMS Graduate Program at UCSF, has
established an aging cohort of C9orf72-/-, Grn-/-, and C9orf72-/-;Grn-/- double KO (DKO) mice. The trainee’s results
showed that C9orf72-/-;Grn-/- DKO mice exhibit age-dependent neuroinflammation and neuronal loss that are
more pronounced than those seen in C9orf72-/- and Grn-/- mice. These findings support the intriguing hypothesis
that simultaneous loss-of-function (LOF) in C9orf72 and GRN genes synergistically disrupts glial homeostasis
and promote neuronal degeneration in an age dependent manner. The scope of this Diversity Supplement
includes (1) to determine the transcriptomic changes regulated by C9orf72 and Grn in glia-neuron homeostasis,
and (2) to expand the transcriptomic data using in situ hybridization (ISH), immunohistochemistry and Western
blots. In addition, this Diversity Supplement includes a well-defined 2-year timeline, a detailed Mentoring
Plan, and Individual Career Development Plan (ICDP) that will significantly enhance the candidate’s research
capabilities and complete her dissertation work on the genetic interactions that cause the age dependent
neurodegeneration in mice. Working within the proposed timeline, this supplement will prepare the candidate for
her long-term career goal as an academic scientist in the field of neuroimmune interaction and
neurodegeneration.

## Key facts

- **NIH application ID:** 10403045
- **Project number:** 3R01AA027074-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Eric J Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $93,282
- **Award type:** 3
- **Project period:** 2018-09-15 → 2022-01-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403045

## Citation

> US National Institutes of Health, RePORTER application 10403045, Diversity Supplement: Single Cell Analyses of Neuroimmune Dysfunctions in the Thalamocortical Circuit in FTLD (3R01AA027074-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10403045. Licensed CC0.

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