The Mouse Liver Microsurgery Core (Core B) will be responsible for conducting liver transplant surgery procedures and post-transplant care in mice in this PPG initiative. The orthotopic liver transplantation (OLT) procedures in mice are technically highly demanding, and the maintenance of surgical technical quality and stability will be the key for the experimental success. Core B therefore will provide all the surgical assistance to the investigators in conducting liver warm ischemia as well as ex vivo liver cold ischemia combined with OLT, as outlined in Project I and Project II. The core will also coordinate experiments among the projects to maximize the use of samples from transplants and minimize the number of animals for transplant surgery. In addition, extra samples from transplants will be stored and maintained as the archive. If the Project requires additional surgical procedures, Core B will also provide support for other surgical needs in the proposals. The laboratory has developed the mouse model of extended hepatic cold storage and OLT a decade ago to study various aspects of innate and adaptive immune responses in organ transplantation. Significant amounts of experience, accumulated data, and available models will enable us to confidently conduct the complicated experiments in this Project.
The specific aims of Core B are as follows:
Aim 1. To provide OLT and local liver IRI surgery and post-transplant care in mice with quality and consistency. The core will be responsible for conducting all the microsurgical OLT/non-transplant procedures and post- transplant care in mice in Project 1 and 2. These procedures are technically demanding, and the Core will assure consistent and reliable surgical outcomes in conducting experiments, as proposed in this PPG.
Aim 2. To coordinate experiments among projects and maximize the use of samples from liver transplants and recipients. The Core will coordinate experiments between Project I and Project II to maximize the use of samples from transplanted animals and thus to minimize the numbers and costs of animals for surgeries.
Aim 3. To store extra samples and maintain the archive. The Core will store and record surplus tissue samples (liver grafts, host tissues, serum) and maintain them as an archive for potential future use.
Aim 4. To provide support for other surgical needs. Core B will provide support for additional surgical procedures (e.g., portal vein injections; i.v. infusions), if needed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI120944-01A1
Application #
9359431
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Kageyama, Shoichi; Nakamura, Kojiro; Ke, Bibo et al. (2018) Serelaxin induces Notch1 signaling and alleviates hepatocellular damage in orthotopic liver transplantation. Am J Transplant 18:1755-1763
Nakamura, Kojiro; Kageyama, Shoichi; Yue, Shi et al. (2018) Heme oxygenase-1 regulates sirtuin-1-autophagy pathway in liver transplantation: From mouse to human. Am J Transplant 18:1110-1121
Kageyama, Shoichi; Nakamura, Kojiro; Fujii, Takehiro et al. (2018) Recombinant relaxin protects liver transplants from ischemia damage by hepatocyte glucocorticoid receptor: From bench-to-bedside. Hepatology 68:258-273
By the Contributors to the C4 Article (Appendix 1) (2018) Current opinions in organ allocation. Am J Transplant 18:2625-2634
Sosa, Rebecca A; Rossetti, Maura; Naini, Bita V et al. (2018) Pattern Recognition Receptor-reactivity Screening of Liver Transplant Patients: Potential for Personalized and Precise Organ Matching to Reduce Risks of Ischemia-reperfusion Injury. Ann Surg :
Kageyama, Shoichi; Hirao, Hirofumi; Nakamura, Kojiro et al. (2018) Recipient HO-1 inducibility is essential for posttransplant hepatic HO-1 expression and graft protection: From bench-to-bedside. Am J Transplant :
Nakamura, Kojiro; Kageyama, Shoichi; Ke, Bibo et al. (2017) Sirtuin 1 attenuates inflammation and hepatocellular damage in liver transplant ischemia/Reperfusion: From mouse to human. Liver Transpl 23:1282-1293
Nakamura, Kojiro; Zhang, Min; Kageyama, Shoichi et al. (2017) Macrophage heme oxygenase-1-SIRT1-p53 axis regulates sterile inflammation in liver ischemia-reperfusion injury. J Hepatol 67:1232-1242