# Center for Quantitative Biology: a focus on “omics”, from organisms to single cells Supplement 4

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2024 · $1,082,397

## Abstract

Dysregulation of normal tissue repair processes can lead to fibrosis, a pathological feature of many diseases,
including chronic inflammatory conditions, autoimmune diseases, and cancer. Excessive accumulation of
extracellular matrix can occur in all tissues, and if progressive, can be fatal. The long-term goal of our group is
to understand the underlying cellular and molecular interactions that contribute to fibrosis, and to use this insight
to develop effective therapeutics to combat this condition, which accounts for up to 45% of all deaths in the
United States each year. Although long assumed to be irreversible, recent evidence from both preclinical studies
and clinical trials demonstrates that fibrosis can be halted and even reversed in vivo. However, there is a
significant gap in the development of safe and effective therapeutic interventions that directly target the mediators
of fibrotic pathogenesis. To address this gap, we have assembled an interdisciplinary team with distinct expertise
to develop and assess the in vivo efficacy of a novel cellular immunotherapy to combat fibrosis.
Fibrosis drives pathology in the chronic autoimmune disease systemic sclerosis (SSc). SSc has the highest case
fatality rate of any systemic autoimmune disease with no validated biomarkers or curative treatments. Multi-
tissue bioinformatic analyses implicate alternatively activated macrophages (MØs) as key drivers of SSc in
multiple end-target organs, suggesting these cells are a common feature across organs and subsets in SSc
patients. Thus, we hypothesize that targeting these pathogenic MØs directly will reduce fibrosis in SSc patients.
To test this hypothesis, we will engineer chimeric antigen receptor (CAR) T cells to secrete anti-fibrotic mediators
and evaluate their therapeutic efficacy in vivo using multi-omic and spatial transcriptomic technologies developed
by the parent award. The development of this therapy, which will target pro-fibrotic MØs that drive fibrosis and
key secreted mediators of fibroblast activation, has potentially significant therapeutic benefit for patients that
suffer from many fibrotic conditions, including cancer. This proposal integrates the diverse expertise of each co-
Project Leader, with Dr. Pioli contributing MØ, fibrosis and SSc expertise, Dr. Huang contributing CAR T cell
therapy engineering expertise, and Dr. Kolling bringing expertise in the development and application of single
cell multi-omics and spatial transcriptomics approaches.

## Key facts

- **NIH application ID:** 11047270
- **Project number:** 3P20GM130454-06S1
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** MICHAEL L WHITFIELD
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,082,397
- **Award type:** 3
- **Project period:** 2019-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11047270

## Citation

> US National Institutes of Health, RePORTER application 11047270, Center for Quantitative Biology: a focus on “omics”, from organisms to single cells Supplement 4 (3P20GM130454-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11047270. Licensed CC0.

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