(provided by the applicant): The over-arching theme of this Program is taking cutting edge technologies for genomics, proteomics and genetics and applying these tools rigorously and critically to the major challenges of transplantation immunology and biology. These efforts in functional genomics are designed to accomplish three complementary objectives: 1) biological discovery, 2) biomarker discovery, and 3) translation of these discoveries to enhance the safety and efficacy of clinical practices in kidney and heart transplantation. All of us believe that the best of translational medicine is advanced by the best of basic research. We believe that serious efforts to achieve fundamental biological understanding of molecular mechanisms must be driven by highly organized teams of scientists and physicians working in close concert. When such collaborative relationships bring science and medicine together successfully, the resulting basic but clinically informed knowledge can be translated directly to preserving health and conquering disease. That effort is what gives meaning to everything we have done in the last funding period and propose to do now. There are many scientific and clinical hypotheses detailed in the individual Projects and Cores. But the central hypothesis of this Program is that multi-dimensional functional genomics will allow us to see the connections between the multiple, parallel mechanisms of immunity that are triggered at the time of a transplant and then evolve in time. In fact, it is this evolution in time that determines the ultimate clinical outcome of the transplant. Thus, if early injury is incompletely repaired, if the immune response determined by both donor and recipient genetics is reactive and progressive or dysregulated, if antibodies are generated and if immunosuppression is ineffective or inadequate for any reason, these elements will drive a progressive, immune/inflammatory destruction of the transplant. It is our mission to minimize this kind of outcome. To achieve this mission we plan to go from basic biology to biomarker signatures validated clinically for diagnosis and prediction of transplant outcomes. Ultimately, we hope to create the genomic tools that will allow physicians to optimize and personalize the safety and efficacy of immunosuppression.

Public Health Relevance

Transplantation is a life-changing and life-saving procedure for patients with endstage kidney and heart disease. However, the truth is that our 10 year graft survivals are only 50% and there is a pressing medical need to improve these results. The causes of this high failure rate will be addressed in this Program using the latest technologies for functional genomics and range from biomarkers for managing immunosuppression to discovery of common, unifying mechanisms for cardiovascular disease risks and chronic rejection.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-MFH-I (M2))
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Nabavi, Nasrin N
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Scripps Research Institute
La Jolla
United States
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Nievergelt, Caroline M; Wineinger, Nathan E; Libiger, Ondrej et al. (2014) Chip-based direct genotyping of coding variants in genome wide association studies: utility, issues and prospects. Gene 540:104-9
Scott-Van Zeeland, A A; Bloss, C S; Tewhey, R et al. (2014) Evidence for the role of EPHX2 gene variants in anorexia nervosa. Mol Psychiatry 19:724-32
Head, Steven R; Komori, H Kiyomi; LaMere, Sarah A et al. (2014) Library construction for next-generation sequencing: overviews and challenges. Biotechniques 56:61-4, 66, 68, passim
Park, Sung Kyu Robin; Aslanian, Aaron; McClatchy, Daniel B et al. (2014) Census 2: isobaric labeling data analysis. Bioinformatics 30:2208-9
Norden-Krichmar, Trina M; Gizer, Ian R; Libiger, Ondrej et al. (2014) Correlation analysis of genetic admixture and social identification with body mass index in a Native American community. Am J Hum Biol 26:347-60
Magdeldin, Sameh; Yamamoto, Keiko; Yoshida, Yutaka et al. (2014) Deep proteome mapping of mouse kidney based on OFFGel prefractionation reveals remarkable protein post- translational modifications. J Proteome Res 13:1636-46
Levitsky, Josh; Mathew, James M; Abecassis, Michael et al. (2013) Systemic immunoregulatory and proteogenomic effects of tacrolimus to sirolimus conversion in liver transplant recipients. Hepatology 57:239-48
Bendjilali, Nasrine; Kim, Helen; Weinsheimer, Shantel et al. (2013) A genome-wide investigation of copy number variation in patients with sporadic brain arteriovenous malformation. PLoS One 8:e71434
Head, Steven R; Mondala, Tony; Gelbart, Terri et al. (2013) RNA purification and expression analysis using microarrays and RNA deep sequencing. Methods Mol Biol 1034:385-403
LaMere, Sarah A; Komori, H Kiyomi; Salomon, Daniel R (2013) New opportunities for organ transplantation research: epigenetics is likely to be an important determinant of the host immune response. Epigenomics 5:243-6

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