# University of Michigan Clinical Autoimmunity Center of Excellence

> **NIH NIH UM1** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $78,000

## Abstract

Abstract
 The current work of the University of Michigan Clinical ACE is built on the hypothesis that organ-
targeted autoimmune diseases depend on unique pathogenic interactions between cells of the immune system
and parenchymal or stromal cells of the target organ, both in disease initiation and target organ destruction.
 Based on advances over the past five years, we propose here a new but related central hypothesis,
that novel, safer and more effective precision-targeted and personalized therapies for autoimmune diseases
can be developed based on insights into two critical and interacting components of autoimmune diseases: 1)
the molecular mechanisms by which target organ stromal and parenchymal cells initiate, orchestrate and
control the evolution and consequences of autoimmune diseases and 2) the critical roles of localization of
unusual lymphocyte populations to target organs in subsets of patients with autoimmune diseases, and the
opportunity for elimination of these cells without substantial impairment of normal host defenses.
 The primary clinical project, CD319 as a novel target for treatment of systemic sclerosis: Treatment with
Elotuzumab, led by Dinesh Khanna, MD, MSc is built on evidence for a pathogenic role of CD4+CD319+
lymphocytes in autoimmune diseases that leads to fibrosis of target organs. We believe that this will be the first
protocol to select subjects for treatment of a human autoimmune disease based on demonstration of
expansion of the targeted lymphocyte subset at trial entry. The alternate clinical project: Tofacitinib for
treatment of photosensitivity and cutaneous inflammation in systemic lupus, led by J. Michelle Kahlenberg,
MD, PhD, is based on our observation that keratinocyte-derived interferon-kappa drives photosensitivity and
cutaneous inflammation in lupus skin. Treatment of these aspects of lupus with a janus kinase inhibitor will be
a step towards more precise targeting of interferon-kappa in lupus. Our collaborative project: Validation of
novel molecular targets for more precise treatment of autoimmune diseases, led by David A. Fox, MD, will
assess expression and function of selected molecules produced by stromal cells in target organs of a broad
range of autoimmune diseases -- AIRE (the autoimmune regulator protein), CD318 (a novel ligand of CD6) and
CD13, which may have major pathogenic roles in human autoimmune conditions. These projects will be
supported by an Administrative Core and a Funds Management Core, and by numerous patient cohorts,
disease-focused clinical programs, core facilities and biorepositories at the University. The Principal
Investigators, Drs. Dinesh Khanna and David A. Fox, work in close collaboration on our existing Clinical ACE
and have substantial experience and productivity in clinical and translational research in systemic sclerosis,
rheumatoid arthritis and other human rheumatic/autoimmune diseases. Together with a team of colleagues at
the University of Michigan and future c...

## Key facts

- **NIH application ID:** 10380100
- **Project number:** 5UM1AI144298-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** David Alan Fox
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $78,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380100

## Citation

> US National Institutes of Health, RePORTER application 10380100, University of Michigan Clinical Autoimmunity Center of Excellence (5UM1AI144298-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380100. Licensed CC0.

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