: 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.
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.
|Meng, Xiangzhi; Riley, Nicole; Thompson, Ryan et al. (2018) Investigate Global Chromosomal Interaction by Hi-C in Human Naive CD4 T Cells. Methods Mol Biol 1712:239-252|
|Gioia, Louis; Siddique, Azeem; Head, Steven R et al. (2018) A genome-wide survey of mutations in the Jurkat cell line. BMC Genomics 19:334|
|Kurian, S M; Velazquez, E; Thompson, R et al. (2017) Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform. Am J Transplant 17:2103-2116|
|Buzby, Jeffrey S; Williams, Shirley A; Schaffer, Lana et al. (2017) Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li-Fraumeni syndrome. Cancer Genet 211:9-17|
|Modena, Brian D; Bleecker, Eugene R; Busse, William W et al. (2017) Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease. Am J Respir Crit Care Med 195:1449-1463|
|Modena, B D; Milam, R; Harrison, F et al. (2017) Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies. Am J Transplant 17:712-723|
|LaMere, Sarah A; Thompson, Ryan C; Meng, Xiangzhi et al. (2017) H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3. J Immunol 199:3158-3175|
|Oetting, W S; Schladt, D P; Guan, W et al. (2016) Genomewide Association Study of Tacrolimus Concentrations in African American Kidney Transplant Recipients Identifies Multiple CYP3A5 Alleles. Am J Transplant 16:574-82|
|LaMere, S A; Thompson, R C; Komori, H K et al. (2016) Promoter H3K4 methylation dynamically reinforces activation-induced pathways in human CD4 T cells. Genes Immun 17:283-97|
|Leventhal, J R; Mathew, J M; Salomon, D R et al. (2016) Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers. Am J Transplant 16:221-34|
Showing the most recent 10 out of 80 publications