# Scleroderma and Gastrointestinal Disease: Insights into Clinical Phenotypes and Disease Pathogenesis

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2022 · $161,679

## Abstract

PROJECT ABSTRACT
Dr. Zsuzsanna McMahan is an Assistant Professor of Medicine in the Division of Rheumatology at Johns Hopkins
University. She obtained her Masters in Clinical Investigation during her rheumatology fellowship training, and
she is currently supported by the Johns Hopkins Clinician Scientist Development Award, the Jerome L. Greene
Foundation, and the NIH Loan Repayment Program. Her co-primary mentors are Dr. Fredrick Wigley, an
internationally recognized rheumatologist with expertise in scleroderma (SSc), and Dr. Livia Casciola-Rosen, an
internationally recognized cell biologist with expertise in the identification of novel autoantibodies. Dr. Antony
Rosen, the Director of the Division of Rheumatology, and Vice Dean for Research at Johns Hopkins, has
significant expertise in translational investigation, and is also part of her mentoring team. Dr. McMahan created
an outstanding Advisory Committee comprised of mentors and consultants who have specific areas of expertise
which are relevant to the proposal. These include Drs. Michelle Petri (longitudinal cohorts) and Clifton Bingham
(patient reported outcomes) in rheumatology, Dr. James Russell in neurology (autonomic dysfunction), and Dr.
Jay Pasricha in gastroenterology (dysmotility). They will provide guidance specific to their area(s) of expertise.
This Advisory Committee is highly enthusiastic about the proposal and fully invested in mentoring Dr. McMahan.
The K23 award will enable Dr. McMahan to gain additional skills important for the conduct of translational
research, develop expertise in the specific niche of neurogastroenterology as it pertains to SSc, and acquire the
data and publications necessary to support a strong R01 application. In this proposal, Dr. McMahan seeks to
precisely define anatomical subsets of SSc gastrointestinal (GI) dysmotility using a radionucleotide-based whole
gut transit study, associate the GI dysmotility subsets with traditional SSc antibodies and antibodies that target
neuromuscular transmission pathways, and finally define novel autoantigens targeted by SSc sera in the GI tract.
Autoantibodies in SSc associate tightly with clinical phenotypes and serve as useful markers in risk stratification.
Currently, risk stratification in SSc GI disease is limited, with few autoantibodies associated with GI
complications. Clearly phenotyping GI subsets will provide a platform to study disease mechanism within more
homogenous SSc GI subsets and provide a framework from which to explore novel therapies in the longer term.
Dr. McMahan has generated strong preliminary data, which supports the following ideas: (1) specific patterns of
GI dysmotility exist in SSc; (2) autoantibodies to neuromuscular transmission pathways are present in patients
with SSc and may associate with specific GI outcomes; and (3) SSc sera from patients with dysmotility recognize
distinct cellular subsets in the GI tract. She has established strong inter-departmental collaborations that will...

## Key facts

- **NIH application ID:** 10374832
- **Project number:** 5K23AR071473-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Zsuzsanna Hortobagyi McMahan
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,679
- **Award type:** 5
- **Project period:** 2018-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374832

## Citation

> US National Institutes of Health, RePORTER application 10374832, Scleroderma and Gastrointestinal Disease: Insights into Clinical Phenotypes and Disease Pathogenesis (5K23AR071473-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10374832. Licensed CC0.

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