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GI & Liver Innate Immune Program

Transformational Research Funding


Gastrointestinal and liver-related diseases account for some of the fastest-growing diseases in our society and cost the U.S. health care system nearly $500 billion annually. Yet there exists a significant unmet need in the diagnosis, treatment and understanding of many GI and liver diseases, including fatty liver disease, eosinophilic esophagitis and inflammatory bowel disease. Many patients have no therapeutic options. A common element of these diseases is dysfunction of the immune system, particularly the innate immune system. 

The innate immune system is a first line of defense against infection by microorganisms and it plays a critical role in resolving inflammation after injury or infection. The innate immune system presents physical and chemical barriers to infectious agents, recruits immune cells to sites of infection, and identifies and removes foreign substances present in organs, tissues, blood and lymph. 

The opportunity 

A digestive disease center focused on innate immunity does not exist on the national level in the United States. In addition, current immune-based therapies lack efficacy in many patients, providing opportunities to develop innate immune-based therapies. The GI and Liver Innate Immune Center will develop biomedical programs, provide pilot funding to develop collaborations, establish an enrichment program to share research discoveries and recruit new investigators to the Anschutz Medical Campus. 

Existing strengths 

The School of Medicine has been home to many notable firsts in the area of digestive and liver disease immunology research and clinical practice, including the world’s first liver transplant, discoveries that improved understanding of adaptive immunity and cytokine biology and the first use of 16S sequencing to characterize the microbiota, a development that has led to the widespread use of this technology in the analysis of microbial populations for health and disease. 

Areas of discovery

Mucosal innate immunity. Accumulating evidence indicates that the unique anatomy and complex architecture of the GI tract and liver provide cues that contribute significantly to both disease progression and resolution of mucosal disease. Compartmentalized tissue and microbe populations within the intestine, for example, result in significant metabolic shifts within these tissue microenvironments. During active inflammatory disease, metabolic demands often exceed supply, resulting in localized areas of metabolic stress.

 Microbiota. Advances in DNA sequence-based technologies now permit genetic analysis of complex microbial populations without the need for prior cultivation. These molecular methods of culture-independent microbiology (‘metagenomics’) and their recent application to studies of the human GI tract in health and disease have served as a paradigm shift in our understanding of host-microbe interactions. Upwards of 40,000 bacterial species are estimated to comprise the collective gastrointestinal microbiome, most of which have not been characterized.

 Hepatic diseases and innate immunity. Innate immunity is critical to the health of the normal liver and

central to the pathogenesis of common hepatic disorders, such as non-alcoholic fatty liver disease (NAFLD). Given the epidemic of obesity in our society, NAFLD and subsequent liver fibrosis have emerged as a major morbidity risk. Innate immunity is central to the development of NAFLD. 

Specific Aims

  • Develop biomedical programs focused on the discovery of new information related to GI and liver innate immunity.
  • Provide pilot funding for developing of new and cutting-edge collaborations studying GI/liver innate immunity on the Anschutz Medical Campus.
  • Establish an extensive enrichment program for the dissemination of new research discoveries.
  • Recruit new investigators from around the world to expand expertise related to innate immune responses in the liver and GI tract.

Leadership 

Biomedical Core   Director/Co-Director(s)
Administrative leadership    Sean Colgan, PhD, Hugo Rosen, MD, Glenn Furuta, MD, Ron Sokol, MD
Innate immunity    Cara Wilson, MD, and Brent Palmer, PhD
Animal models Holger Eltzschig, MD, PhD, and Cynthia Ju, PhD
Host-microbe/microbiota    ​Cathy Lozupone, PhD, and Dan Frank, PhD
GI/liver tissue biorepository Lucy Golden, PhD, Ed DeZoeten, MD, PhD, and Mark Gerich, MD
Inflammatory cancer models Wells Messersmith, MD, and Peter Dempsey, PhD​