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Molecular Profiling Immunomodulatory Intervention

Funding:

National Institutes of Health Cooperative Agreement - Subcontract with the University of Pennsylvania

Principal Investigator:

Stuart J. Knechtle, MD

Project Summary:

We propose noninvasive gene expression profiling for the characterization of innate immunity and adaptive immunity pertinent to solid organ transplantation. We also propose interventional trials that address critical unmet needs; the clinical studies are underpinned by mechanistic studies.

Our proposals were stimulated by our single center observations and by evolving literature that mRNA profiling of peripheral blood cells/urinary cells are diagnostic of allograft status. Our identification that mRNA profiles of intraoperative renal allograft biopsy specimens predict acute rejection and renal allograft functional outcome has informed our research design.

As a participant of cooperative multi-site kidney-specific and trans-organ studies to determine whether common molecular profiles can characterize inflammatory and immune responses, and provide better means to monitor and apply interventional modalities aimed at improved organ function.

In renal allograft recipients, we will investigate:

  1. whether mRNA profiling of donor kidneys predict adverse outcomes such as acute rejection and impaired function
  2. whether acute rejection can be predicted by sequential mRNA profiling of urinary cells;
  3. whether preemptive treatment, based on mRNA profiles, prevents acute rejection and preserves GRF, and
  4. whether mRNA profiles can be used to guide the withdrawal of calcineurin inhibitors in stable recipients.

Studies in diverse groups of transplanted organs will focus on the interrelations of inflammatory response and alloreactivity, and their impact on organ function and recurrent disease.

In recipients liver allografts, we will explore:

  1. whether mRNA profiling of donor livers and recipient PBL reflect the intensity of inflammatory response, and predict the probability of acute rejection and organ function
  2. whether mRNA profile can determine the outcome of steroid-free immunosuppression of recurrence HCV.

These mechanistic assays will be carried out with the use of kinetic (real) time quantitative PCR assays and in select instances with the use of nucleic acid based microarrays, and are expected to be applied in the routine clinical care of the transplanted population.

 

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Transplantation - University of Wisconsin Department of Surgery
First published: 07/15/02 Last updated: 10/13/08 webmaster@surgery.wisc.edu
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