# Ancillary studies to define dysregulated immune and fibrotic pathways in a well-characterized morphea cohort

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $376,842

## Abstract

PROJECT SUMMARY
Morphea is a disfiguring autoimmune disease of the skin and underlying tissue. An unbalanced inflammatory
response leads to fibrosis and atrophy of the deeper tissue, causing physical and psychological disability.
Available therapies for morphea are not always efficacious and are often associated with substantial side
effects. One of the biggest barriers to the development of new treatments is a lack of studies examining the
pathophysiology of morphea, the initial step that leads toward the development of more directed and
efficacious therapies. The Morphea in Adults and Children (MAC) and National Registry for Childhood Onset
Scleroderma (NRCOS) registries, led by the principal investigators (Jacobe and Torok, respectively), have
already begun to address this problem. Working together, we have investigated the protein expression and
bulk transcriptional profile associated with morphea in both children and adults using protein assay, cytometry,
and microarray/RNA sequencing. These data indicate that fibrosis in morphea is driven by inflammation
through a network of IFN-γ mediated genes. Despite this progress, the pathogenesis of morphea, including the
exact cell populations’ producing this IFN-γ over expression, needs to be examined in depth before new
treatments can be tested. That is the goal of this proposal.
Our studies will leverage both the unique resources of the MAC and NRCOS registries (the largest in the
world), which are supported by a Parent Observational Cohort study grant (NIAMS R01), and the
multidisciplinary and complementary expertise of the investigators (including facilities at UTSW Medical Center
and the University of Pittsburgh) to conduct detailed transcriptional and mechanistic studies to fully investigate
transcriptional profiles of likely pathogenic cell types and study the immunological effects of key molecules in
fibroblast cultures and co-culture systems. The objectives of the proposed studies are to: 1) further define
dysregulated immune pathways in morphea via transcriptomic analyses, 2) determine the association of these
gene signatures to validated clinical measures and disease course to evaluate their role as biomarkers in
morphea, 3) identifying inflammatory cell subsets that express these IFN-γ mediated genes, which are likely
the pathogenic cell subtypes, 4) determine fibroblast subsets and their interaction with pathogenic
inflammatory cells, 5) and define the pathogenic pathways that enable the disease, by first utilizing human
fibroblast cultures. The conduct of these studies will not only probe morphea to find the underlying disease
mechanism, but will also produce promising targets for development of biomarkers and new therapies.

## Key facts

- **NIH application ID:** 10136199
- **Project number:** 1R01AR078560-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Heidi T Jacobe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,842
- **Award type:** 1
- **Project period:** 2021-03-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136199

## Citation

> US National Institutes of Health, RePORTER application 10136199, Ancillary studies to define dysregulated immune and fibrotic pathways in a well-characterized morphea cohort (1R01AR078560-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10136199. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*