Computational Core: Biostatistical Analysis and Network Modeling Core Co-Directors: David Gjertson PhD and Alexander Hoffmann PhD SUMMARY This application proposes three research Projects and three Cores for shared resources led by investigators at the University of California Los Angeles (UCLA), centered around the theme of investigating innate-adaptive immunoregulation in liver transplant ischemia/reperfusion Injury (IRI). Projects I and II focus on modulation of IRI immune responses following hepatic grafting in syngeneic and allogeneic murine models, respectively; whereas, Project III concentrates on elucidating the role of IRI on immunoregulation following human OLT. Core C provides data management, biostatistical and computational expertise required for the proper analysis and network modeling of data generated by Projects. Statistical and mechanistic modeling will allow the integration of diverse datasets to develop predictions, and may generate new findings and insights by comparing the datasets from the three types of liver transplants. Services will be provided in the following areas: ? Data quality control, monitoring and management. ? A central infrastructure for data preprocessing of high throughput molecular data. ? Biostatistical design, statistical monitoring of studies to ensure interpretability of results. ? Statistical analysis and interpretation of diverse datasets. ? Development of biostatistical methodology for statistical problems in these projects. ? Modeling molecular networks to interpret transcriptome data and provide knowledge-based dimensionality reduction ? Modeling the immune-cell dynamics to interpret immune-phenotyping datasets and integrate molecular and cellular scale data and analyses. ? Assistance with manuscript preparation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI120944-01A1
Application #
9359432
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; 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 :
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
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