# Precision Medicine in Inflammatory Bowel Disease: Refining the Clinical and Genomic Predictors of Response to Anti-IL-12/23 Therapy

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $167,165

## Abstract

ABSTRACT
Crohn’s disease (CD) is a chronic immune-mediated gastrointestinal disease characterized by significant
clinical and molecular heterogeneity. The clinical heterogeneity is evidenced by the wide variation in disease
location, severity, and behavior. The molecular heterogeneity is evidenced by the numerous genetic risk loci
which have been identified to date. Fortunately, there are an increasing number of therapeutic options for the
treatment of CD including blockade of tumor necrosis factor  and blockade of IL-12/23 signaling.
Unfortunately, patients rapidly cycle through medications, often due to lack of response, further increasing
morbidity and healthcare costs. Therefore, there is an urgent need for data matching the mechanism of the
disease to the treatment target to guide treatment selection. Our long-term goal is to improve first-line therapy
selection in CD as more therapies become available at biosimilar prices. In this career development proposal, I
will focus on acquiring data which provides a deeper understanding of the clinical and molecular attributes
which associate with response to anti-IL-12/23 therapy to improve drug positioning and first-line therapy
selection for this class of therapy in CD. We have shown that CD patients with autoimmune skin disease
preferentially respond to anti-IL-12/23 therapy. We will utilize machine learning to identify additional clinical
patterns which associate with preferential response to therapy, then develop a decision tool to aid clinicians in
selection of patients for first-line anti-IL-12/23 therapy. Then, we will investigate genomic predictors of
response using both a targeted and genome wide approach. Finally, we will identify transcriptional modules
which associate with drug response which will yield insight into the tissue cell signatures which associate with
differential response. The scientific and training objectives outlined will provide me with the expertise needed to
pursue independent investigation in the field of precision medicine, with a specific emphasis on the utilization
of large scale clinical and genomic datasets to predict prognostic and therapeutic outcomes in CD.

## Key facts

- **NIH application ID:** 10829459
- **Project number:** 5K08DK133640-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Kelly Colleen Cushing-Damm
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $167,165
- **Award type:** 5
- **Project period:** 2023-04-17 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829459

## Citation

> US National Institutes of Health, RePORTER application 10829459, Precision Medicine in Inflammatory Bowel Disease: Refining the Clinical and Genomic Predictors of Response to Anti-IL-12/23 Therapy (5K08DK133640-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10829459. Licensed CC0.

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