# Molecular Profiling of Spinal Disease Progression in Ankylosing Spondylitis

> **NIH NIH K23** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $162,540

## Abstract

PROJECT SUMMARY/ABSTRACT
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis with a predilection for the spine and sacroiliac
joints, affecting 0.5-0.6% of the US population, that causes substantial morbidity and work-disability. AS spinal
damage is strongly related to poor physical function independent of disease activity - severe spinal disease
causing significant physical limitations. However, the course of AS spinal disease is highly heterogeneous,
ranging from damage limited to sacroiliac joints to complete spinal fusion. We characterized AS patients'
longitudinal spinal progression over a 15-year interval, revealing 4 endotypes/groups of spinal progression.
However, clinical variables poorly discriminated patients who developed severe spinal disease compared to
the other spinal disease groups. Our goals in this proposal are to i) characterize the peripheral blood
molecular profile of AS spinal disease and ii) develop prediction tools combining clinical and molecular
biomarkers prognosticate AS spinal disease before irreversible damage has occurred.
The PI's preliminary data indicate that peripheral blood molecular markers in combination with genetic and
clinical variables improve prognostication of long-term spinal outcomes. Aim 1 of the proposal is designed to
further profile the transcriptomic signatures associated with AS spinal disease progression through next-
generation bulk and single-cell RNA-sequencing. Aim 2 will use high-throughput proteomics to profile AS
patients' sera with known AS spinal trajectories. Aim 3 will use Bayesian multivariable modeling and
Integrative analysis of clinical, genetic, gene expression and proteomic datasets to generate prediction models
of AS patients' risk of severe spinal disease.
The Pl is an MD Rheumatologist with the long-term goal of becoming an independent investigator focused on
AS pathogenesis and outcomes. The proposed research and training plan will help the Pl to develop
proficiency in analyses of molecular data and in systems medicine modeling. Equally important are the career
development goals of enhancing skills in data presentation, grant writing and project management in
preparation for scientific independence. These goals will be achieved through a combination of mentorship,
formal didactic instruction, and experimentation. The work will be performed in an excellent institutional
environment with mentorship from Dr.Shervin Assassi, a leader in molecular profiling in systemic sclerosis, and
additional guidance from co-mentors with expertise in ankylosing spondylitis, bioinformatics and immunology.
This award will accelerate the Pl's research as well as career development into an independent and productive
clinician scientist in rigorously designed and conducted translational research.

## Key facts

- **NIH application ID:** 10785663
- **Project number:** 1K23AR083506-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Mark Chiawei Hwang
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $162,540
- **Award type:** 1
- **Project period:** 2024-02-12 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785663

## Citation

> US National Institutes of Health, RePORTER application 10785663, Molecular Profiling of Spinal Disease Progression in Ankylosing Spondylitis (1K23AR083506-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10785663. Licensed CC0.

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