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Projects of COBRE Digestive & Liver Disease

Transforming Digestive & Liver Research Together

At the Center of Biomedical Research Excellence (COBRE) in Digestive and Liver Disease, our projects foster innovation and collaboration across scientific disciplines to advance understanding and treatment of digestive and liver conditions. From pilot programs that seed bold ideas to research that shapes national impact, the center empowers investigators to pursue discovery with purpose and excellence. These initiatives engage faculty, postdoctoral fellows, and trainees in creating pathways to groundbreaking scientific and clinical advances.

Current Projects and Leaders

A cohesive set of innovative projects that aim to define how metabolic signaling pathways regulate disease-relevant cellular interactions across digestive and metabolic systems

Project 1

Research Project Leader
Evan Delgado, Ph.D., Department of Regenerative Medicine and Cell Biology

Overview
This project investigates how tumor metabolism shapes immune suppression and therapeutic resistance in hepatocellular carcinoma (HCC). Specifically, it focuses on glutamine metabolism regulated by glutamine synthetase and its impact on tumor-associated macrophage function in β-catenin-mutated HCC.

Specific Aims

  • Define how loss of glutamine synthetase affects macrophage function
  • Determine how macrophage metabolism regulates immunotherapy response

Research Approach
Genetically engineered mouse models, flow cytometry, and single-cell sequencing will be used to define macrophage phenotypes and immunotherapy responses.

Use of the Center's Core Resources

  • Animal Models Core
  • Imaging Core
  • Genomics Core

Innovation

  • Links metabolism to immune suppression
  • Targets macrophage-driven immunotherapy resistance

Expected Impact
Provides new strategies to improve immunotherapy in liver cancer.

Project 2

Research Project Leader
Hailong Zhang, Ph.D., Department of Pharmacology and Immunology 

Overview
This project defines how the enteric nervous system regulates epithelial biology and host defense through serotonin signaling to intestinal stem cells.

Specific Aims

  •  Define how neurons sense pathogens
  • Determine how serotonin regulates stem cells

Research Approach
Combines infection models, genetic models, and single-cell approaches to define neuroepithelial signaling

Use of the Center's Core Resources

  • Animal Models Core
  • Imaging Core
  • Genomics Core

Innovation

  • Establishes neuroepithelial signaling paradigm
  • Links neurons to epithelial regeneration

Expected Impact
Identifies new therapeutic strategies for infection and intestinal disease

Project 3

Research Project Leader
Tim Barnoud, Ph.D., Department of Biochemistry and Molecular Biology

Overview
This project investigates how a p53 polymorphism regulates ferroptosis and contributes to cancer disparities.

Specific Aims

  • Define ferroptosis differences in p53 variants
  • Identify metabolic drivers of resistance

Research Approach
Uses cellular models and mouse models to study redox regulation of ferroptosis

Use of the Center's Core Resources

  •  Genomics Core
  • Animal Models Core

Innovation

  •  Connects genetics to redox biology
  • Defines ferroptosis regulation

Expected Impact
Provides insight into mechanisms of cancer susceptibility and therapy response

Project 4

Research Project Leader
Jennifer Stancill, Ph.D., Department of Biochemistry and Molecular Biology

Overview
This project studies how peroxiredoxin and redox systems regulate insulin production and β-cell function.

Specific Aims

  • Define redox control of insulin synthesis
  • Determine protective mechanisms in β-cells

Research Approach
Uses cellular and molecular approaches to study oxidative stress and insulin secretion

Use of the Center's Core Resources

  • Cell Models Core
  • Genomics Core

Innovation

  • Defines redox control of endocrine function
  • Links oxidative stress to diabetes

Expected Impact
Identifies targets to preserve β-cell function in diabetes

Empowering the Next Generation of Investigators

The Pilot Project Program accelerates bold ideas by empowering MUSC scientists to explore novel approaches in digestive and liver disease research. Through competitive funding, mentorship, and collaboration, the program transforms early-stage concepts into promising foundations for major grants and future breakthroughs.

Learn About the Program

Advancing Innovation Through Shared Knowledge

The Enrichment Series brings leading voices in science and medicine to MUSC, inspiring collaboration and sparking discovery. From the Digestive Disease Seminar Series to the annual Scientific Retreat, these experiences connect investigators, foster mentorship, and elevate innovation in digestive and liver research.

Learn About the Series

Project Archive

The research of the center's recently supported project leaders continues to shape the field of digestive and liver disease.

Project Leader

Antonis Kourtidis, Ph.D.

Overview

Project Details

Project Leader:

Jorge Munera, Ph.D.

Overview:

Project Details

Project Leader:

Chad Novince, Ph.D.

Overview:

Project Details

Project Leader:

Eric Meissner, M.D., Ph.D.

Overview:

Project Details

Research Project Leader

Aaron Hobbs, Ph.D.

Overview

Dr. Meissner’s research defined how type-I and type-III interferon (IFN) signaling pathways interact to regulate antiviral immunity in hepatocytes. The project tested the hypothesis that type-III IFNs (IFNλ) modulate type-I IFN responses through induction of negative regulatory pathways, thereby shaping the balance between effective antiviral defense and chronic inflammation. Using hepatitis C virus (HCV) as a model system, this work established a framework for understanding how interferon signaling contributes to viral persistence, clearance, and treatment response in liver disease.

Specific Aims

  • Define how canonical and non-canonical IFNLR1 receptor isoforms regulate type-I interferon signaling
  • Determine how the IFNL4 genetic polymorphism (rs368234815) drives variability in hepatocyte antiviral responses

Research Approach

The project employed induced pluripotent stem cell–derived hepatocytes (iHeps) combined with CRISPR-Cas9 genome editing to dissect interferon signaling pathways in a genetically controlled system. IFNLR1 receptor expression and isoform composition were manipulated to determine their impact on downstream signaling and interferon-stimulated gene expression. Genetic engineering of the IFNL4 locus enabled direct testing of clinically relevant variants that influence antiviral responses. Functional assays measured cytokine signaling, gene expression, and response to viral and innate immune stimuli.

Use of the Center's Core Resources

Cell Models Core:

  • Generation of iPSC-derived hepatocytes and CRISPR-engineered cell lines

Advanced Imaging Core:

  • Analysis of interferon signaling dynamics and protein interactions

Administrative and Biostatistics Core:

  • Study design, data analysis, and training support

Innovation

  • Establishes a mechanistic link between type-III and type-I interferon signaling in hepatocytes
  • Defines the functional role of IFNLR1 receptor isoforms in regulating immune responses
  • Uses CRISPR-edited iPSC-derived hepatocytes to model genetic variation in antiviral immunity

Impact and Outcomes

This project provides critical insight into how interferon signaling is regulated during chronic viral infection and how genetic variation influences patient outcomes. By defining mechanisms through which type-III interferons suppress or modulate type-I responses, this work informs strategies to therapeutically manipulate immune pathways in diseases such as hepatitis B, hepatitis C, and HIV. Participation in the CDLD program supported Dr. Meissner’s transition to independence and advanced his research program in viral immunology and translational hepatology.

Research Project Leader
Mindy Engevik, Ph.D.

Overview
Dr. Engevik’s research focused on defining how commensal bacteria regulate intestinal inflammation through metabolic interactions with the host epithelium. This project centered on the bacterium Bifidobacterium dentium and its production of γ-glutamylcysteine, a precursor to the antioxidant glutathione.

The work tested the hypothesis that microbially derived γ-glutamylcysteine enters epithelial cells, elevates glutathione levels, reduces oxidative stress, and suppresses pro-inflammatory signaling. The study established a novel framework linking diet, microbial metabolism, and epithelial redox biology in inflammatory bowel disease (IBD).

Specific Aims

  • Determine whether B. dentium–derived γ-glutamylcysteine reduces inflammation and elevates epithelial glutathione in chronic colitis models.
  • Define how microbial γ-glutamylcysteine production and host signaling pathways regulate inflammatory responses in human intestinal organoids.

Research Approach
The project integrated in vivo mouse models, microbial metabolism studies, and human organoid systems. Chronic colitis was evaluated using IL-10 knockout mice treated with live B. dentium, mutant strains, or γ-glutamylcysteine under defined dietary conditions. These studies assessed inflammation, reactive oxygen species (ROS), glutathione levels, and cytokine responses. Complementary in vitro approaches used human colonic organoids and epithelial cell systems to track uptake of microbial metabolites, define glutathione pathway activation, and quantify inflammatory signaling including NFκB-driven cytokines. Multi-omics, metabolomics, and live imaging approaches were used to characterize bacterial metabolite production and host responses.

Use of the Center's Core Resources

  • Animal Models Core: Chronic colitis models and microbial colonization studies
  • Advanced Imaging Core: Live ROS imaging and epithelial analysis
  • Cell Models Core: Human intestinal organoid development and manipulation

Innovation

  • Identifies microbial γ-glutamylcysteine as a novel regulator of epithelial redox balance
  • Links diet, microbiome metabolism, and host antioxidant pathways in IBD
  • Introduces a microbiota-based therapeutic strategy to elevate glutathione in the colon

Impact and Outcomes
This project demonstrated that microbial metabolites can directly regulate epithelial oxidative stress and inflammation, providing new insight into host–microbe interactions in the gut. By establishing γ-glutamylcysteine as a modulator of glutathione and inflammatory signaling, the work highlights a potential therapeutic pathway for treating IBD through microbiome-targeted or dietary strategies.

Participation in the center's program supported Dr. Engevik’s transition toward independent funding and advancement as a leader in microbiome–host interaction research.

Research Project Leader

Amy Engevik, Ph.D.

Overview

Dr. Engevik’s research project focused on defining how epithelial trafficking mechanisms regulate intestinal barrier function and inflammation. Specifically, this work investigated the role of the molecular motor Myosin 5b in delivering intestinal alkaline phosphatase (IAP) to the apical surface of epithelial cells, where it serves as a key anti-inflammatory enzyme. The project was driven by the hypothesis that inflammation-associated loss of Myosin 5b disrupts IAP localization, impairing detoxification of pro-inflammatory microbial signals and increasing susceptibility to intestinal injury. This work established a novel mechanistic link between epithelial trafficking, microvilli function, and inflammatory bowel disease (IBD) pathogenesis.

Specific Aims

  • Determine whether loss or reduction of Myosin 5b increases susceptibility to colitis in vivo
  • Define how impaired Myosin 5b function alters epithelial inflammatory responses and cytokine production

Research Approach

The project combined genetically engineered mouse models, human and murine intestinal organoids, and in vitro epithelial systems to define the role of Myosin 5b in intestinal inflammation. Conditional and heterozygous Myosin 5b mouse models were used to evaluate susceptibility to DSS-induced colitis and to define epithelial and immune responses in vivo. Complementary organoid-based systems were used to interrogate epithelial-intrinsic mechanisms, including IAP localization, cytokine production, and responses to bacterial ligands such as LPS and flagellin. Advanced imaging and molecular analyses were applied to define microvilli structure, protein trafficking, and inflammatory signaling pathways.

Use of Center Core Resources

  • Animal Models Core: Generation and analysis of Myosin 5b genetic models and colitis studies
  • Cell Models Core: Development and gene editing of intestinal organoid systems
  • Advanced Imaging Core: High-resolution imaging of microvilli structure and protein localization

Innovation

  • Identifies a novel role for Myosin 5b in regulating intestinal immune homeostasis
  • Links epithelial trafficking defects to inflammatory bowel disease mechanisms
  • Introduces the concept that microvilli actively regulate inflammation via IAP localization

Impact and Outcomes

This project provided new insight into how epithelial cell biology contributes to intestinal inflammation by identifying Myosin 5b as a regulator of anti-inflammatory signaling at the mucosal surface. The findings established a new framework for understanding microvilli dysfunction in IBD and highlighted IAP trafficking as a potential therapeutic target. Participation in the COBRE in Digestive and Liver Disease program supported Dr. Engevik’s transition to independent funding, contributing to successful grant applications and the development of a research program focused on epithelial biology and intestinal disease.

Project Leader:

Je‑Hyun Yoon, Ph.D.

Overview:

Project Details