The focus of our laboratory effort is the integrated study of transplantation medicine using the latest tools of functional genomics, immunology and cell biology. Transplantation spans the challenges of islet transplantation for diabetes, kidney and liver transplantation for end stage organ failure, adult stem cells for therapy of genetic models of organ failure and therapeutic gene delivery with retroviral and AAV vectors. We also continue to develop new animal and cell culture-based models for transplantation to test novel therapeutic approaches and discover the underlying biology and molecular mechanisms driving as well as regulating immunological rejection and responses to gene therapy. We are also fascinated by the challenge and complexity of engrafting transplanted or gene-modified stem cells and tissues into a new host. Our functional genomics work includes whole genome transcription profiling, alternative splicing arrays, microRNA studies, high-throughput next generation DNA sequencing and shot gun tandem mass spectrometry proteomics as well as developing computational tools such as MirMiner. We have applied these tools to studying the molecular mechanisms of T and B cell activation and regulation, to detailed studies of transcriptional regulation, to studies of the phosphoproteome of activated lymphocytes, to developing novel blood cell biomarkers for predicting rejection and managing immunosuppressive therapy in patients with kidney transplants, to profiling liver transplants to understand the potential of tissue regeneration and to human islets to understand the molecular basis of a functional cell transplant. In all our work, the objective is to work in a multi-dimensional genomic space created by an ongoing and iterative integration of the latest technologies with cell-based, preclinical animal models and human clinical studies. At each step we strive to design studies that often move from clinical patient samples to cell assays that effectively test and validate basic molecular mechanisms and identify their regulatory elements in the context of what is known and what we can discover to basic molecular studies of mechanisms and structure. When this effort is successful, we can construct cell response systems and map the interactions of multiple genes into functional networks, both driving and regulating the immunity, inflammation, tissue injury and regeneration that determine the final outcomes of any cell or organ transplant.
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Molly Baber Research Fund for Diabetes and Transplantation Medicine
Transplant Genomics Collaborative Group (TGCG)
National Instititute of Allergy and Infectious Diseases (NIAID)
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Last Updated 03/04/2009 |
