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.
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.
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
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.
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.
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.
- 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
- 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
||Sean Colgan, PhD, Hugo Rosen, MD, Glenn Furuta, MD, Ron Sokol, MD|
||Cara Wilson, MD, and Brent Palmer, PhD|
||Holger Eltzschig, MD, PhD, and Cynthia Ju, PhD|
||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|