About the Yale Liver Center

The Yale Liver Center's mission is to enhance knowledge of the etiology, diagnosis and treatment of liver diseases and other related disorders of the digestive system, thereby advancing the nation's public health. It does so by simulating both basic, translational and clinical research in this discipline at the University, establishing core research facilities for use by multiple liver investigators, by giving pilot feasibility awards to support new investigators and ideas, and through an enrichment program that seeks to enhance collaborative opportunities among Yale researchers with investigators from elsewhere and with the community.

The major goals of the Center continue to be:

1. To stimulate multi-disciplinary interactions
2. To provide an exciting in-depth training environment for pre- and post-doctoral candidates
3. To efficiently organize time consuming or costly techniques and procedures in Core Facilities for multiple users
4. To stimulate basic scientists to direct their talents and technology to specific areas of research interests in the Center
5. To promote important new research and training opportunities through pilot feasibility projects
6. To stimulate translational research from the bench to clinical application at the bedside
7. To create an intellectual environment within the institution and to foster collaborative efforts with individuals within as well as beyond the institution whose expertise enhances our progress

To accomplish these goals the Center has:

• Organized costly techniques and procedures in Core Facilities for multiple investigator use
• Used small pilot feasibility grants to enhance new avenues of investigation both for senior trainees/junior investigators, as well as for established investigators when these efforts represented a departure from their current focus of investigation
• Pursued an active scientific enrichment program with weekly to monthly seminars often given by invited outside scientists whose work was of particular interest to the Center membership. Center retreats, ‘reverse’ mini-sabbaticals and special symposia have augmented this enrichment program

The Liver Center was established in 1984 and was constructed around six Core Facilities, which at that time included:

1. An Administrative Core
2. A Hepatocyte Isolation and Cell Culture Core
3. A Liver and Splanchnic Organ Perfusion Core
4. A Membrane Isolation Core
5. A Morphology Core
6. A Clinical Core.

With successive competitive renewals, the Center has undergone several periods of reorganization as the science of the Center and the needs of our members has evolved. This evolution also has been guided by the recommendations of our External Advisory Board, suggestions from previous NIH review groups, and more recently by annual member surveys as well.

The Liver Center now consists of four Core Facilities:

1. An Administrative Core
2. A Cellular and Molecular Physiology Core
3. A Morphology Core
4. A Clinical-Translational Core.

The evolution of the Liver Center is reflected in the evolution of each of these cores. For example, the perfusion and cell isolation and culture components were combined into a single Cellular Molecular Core in 1996-1997 as fewer isolated perfused liver preparations were requested while the use of the cell isolation and culture component of the Core increased significantly. On the other hand, services in this Core then evolved to include the isolation of sinusoidal endothelial, Kupffer, and stellate cells and intrahepatic lymphocytes as well as previously established procedures for isolating hepatocytes and bile duct epithelial cells. Currently, cell isolations and animal surgery often are performed on genetically derived mice, and the core now offers liver organoids derived from murine and human iPSC’s as well. Similarly, electron microscopy initially was the principal imaging technology offered through the Morphology Core, but this has become progressively de-emphasized while newer, cutting edge confocal, multiphoton, and now super-resolution, swept-field, and lightsheet microscopy techniques are now the most wideley used resources by Center members. When the NIH guidelines were changed to encourage inclusion of a Clinical Core Component, a Clinical-Translational Core was organized to function as a Clinical Resource for Center members primarily engaged in clinical research. As a result, the initial areas of focus of this Core had been to provide support for developing and maintaining clinical protocols, building a patient registry and bio-specimen bank, and providing biostatistics support. However, to stimulation translational research among our basic scientists and enhance collaboration between our basic and clinical investigators, we have shifted efforts to improve access for basic scientists to patient data and bio-specimens, and we have developed a resource to store PBMC’s from specific types of patients for the Cellular and Molecular Core to be able to derive iPSC’s for disease-specific human liver organoids. Biostatistical assistance continues to be provided as well and continues to be heavily used, but we now have also added a bioinformatics component because of increasing demand for this type of analysis by our members.

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