Research Group

  • Dr. Robert A. Kirken, Principal Investigator
  • Dr. Stanislaw M. Stepkowski, Associate
  • Dr. Karras James, Collaborator
  • Dr. Federica Pericle, Collaborator


  • The University of Texas Health Science Center at Houston, Houston, USA


  • Identification of a Novel Protein Involved in Rejection of Transplanted Organs

There is an increasing need for successful transplantation of solid organs. Organ failure caused by complications to aging, autoimmune and inflammatory disease represents a rising health care problem and challenge to modern medicine. While major progress in organ transplantation has been achieved due to immunosuppressive drugs, their clinical value is limited due to associated toxicities. It is therefore a critical need to develop alternative strategies to achieve allograft acceptance. To provide a molecular rationale for innovative treatment strategies, new aspects of T-cell signaling must be explored. While current immunosuppressants (CsA and FK506) block T-cell receptor activation and interleukin-2 (IL-2) production, they are useless on T-cells that escape this regime, only to expand and promote chronic organ rejection. We propose to focus on novel signaling molecules downstream of the IL-2 receptor to block T-cell expansion. We reported that two related transcription factors, Stat5a and Stat5b, cannot be activated by IL-2 in T-cells isolated from immunocompromised tumor-bearing mice and HIV-infected patients, suggesting they are critical to T-cell regulation. In T-cells, we mapped IL-2-inducible tyrosine/serine phosphorylation sites in Stat5a/b and identified a novel pharmaceutical agent that blocked these pathways and consequently T-cell proliferation. Preliminary evidence suggests that temporary administration of this drug can promote rat heart transplant survival. Recent evidence that Stat5a/b knockout mice are immunosuppressed with T-cells unresponsive to IL-2 provides additional support for our model. Here, we will test the principal hypothesis that disruption of Stat5a/b signalling pathways prevents T-cell expansion and allograft rejection by three related specific aims designed to inactivate Stat5a/b by 1) our novel drug, 2) anti-sense and 3) dominant-negative gene variants delivered by viral and non-viral methods. At the conclusion of this research we expect to have established that inhibition of Stat5 transcription factors represents a viable therapeutic strategy to promote acceptance of transplanted organs.