# Predictive modeling of CD-68 inflammatory and anti-inflammatory chromatin packing domains for personalized biomarker discovery

> **NIH DK K23** · NORTHWESTERN UNIVERSITY · 2026 · $187,038

## Abstract

Project Summary/Abstract
Ulcerative colitis (UC) is a complex disorder impacting millions of people worldwide resulting in significant costs,
chronic debilitating symptoms, and complications such as colon cancer. Even with biologic therapies targeting
immune signaling pathways, variability in patient responses is highly prevalent and remission rates remain low
(~40%). Therefore, personalized biomarker development is an area of unmet clinical need. Macrophages have
been identified as a crucial intermediary of pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes in UC.
Due to the significant overlap between M1 and M2 signaling even in histologically identical tissues, biomarkers
focused on transcriptomics alone are limited. Chromatin, the genome folded into 3-D, regulates how genes
interact with transcription factors and polymerases to synthesize RNA. Since cytokine signaling converges on
transcription-factor cascades, understanding chromatin structure in UC may serve as a rational framework for
biomarker development. The goal of this proposal is to establish a cohesive framework that links transcriptomic
states with chromatin structure for biomarker development in UC. Preliminary work shows that chromatin packing
domains are the primary regulator of transcriptional reactions in cells. The stochastic returns-excluded volume
(SR-EV) model can produce the structure of chromatin packing domains observed on electron microscopy at
high-throughout (>100k independent configurations). We hypothesize that it’s possible model and predict
macrophage transcriptomic behavior in UC by combining SR-EV with in situ transcriptomic and chromatin
measurements. We test this hypothesis through three separate but inter-related aims. Aim 1 focuses on
expanding the capabilities of SR-EV to predict domains associated with M1 and M2 macrophage transcriptomic
patterns. Aim 2 studies the mechanisms governing packing domain formation in macrophages and the ability to
manipulate expression 

## Key facts

- **NIH application ID:** 11374573
- **Project number:** 5K23DK144661-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Luay Matthew Almassalha
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** DK
- **Fiscal year:** 2026
- **Award amount:** $187,038
- **Award type:** 5
- **Project period:** 2025-08-01T00:00:00 → 2030-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11374573

## Citation

> US National Institutes of Health, RePORTER application 11374573, Predictive modeling of CD-68 inflammatory and anti-inflammatory chromatin packing domains for personalized biomarker discovery (5K23DK144661-02). Retrieved via AI Analytics 2026-07-23 from https://api.ai-analytics.org/grant/nih/11374573. Licensed CC0.

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