Research Group

  • Dr James Reynolds, Principal Investigator
  • Dr Silvia Perez-Protto Silvia, Collaborator
  • Dr Hari Baskaran, Collaborator
  • Dr Daniel Lebovitz, Collaborator
  • Dr Robert Schilz, Consultant
  • Dr Jonathan Stamler, Consultant
  • Dr Jeffrey Ustin, Consultant


  • Case Western Reserve University, Cleveland, USA


  • Understanding the macro and molecular effects of donor support protocols to improve the function of transplantable organs

Transplantation is an accepted intervention to correct innate organ failure but a successful outcome is highly dependent upon the physiologic status of the donor. Stressors placed upon organs, particularly brain death (BD), are believed to affect recipient survival rates and are also significant contributors to the poor procurement rates (10-30%) for some organs such as the heart and lungs from consented donors – (150) a disheartening figure when one considers how much organ demand outstrips availability. Clearly better methodologies are needed to optimize support of the donor after BD.

We believe an unexplored area is the effect of BD on the status of S-nitrosothiols (SNOs), small molecules that act in the body to control oxygen delivery, cellular activity, and organ function. In fact SNO interactions with the body's proteins (called protein S-nitrosylation) is the major mechanism through which the cellular influence of nitric oxide (NO) is exerted. Thousands of proteins have been identified where activity decreases or increases in response to the addition or removal of NO. This is important for donor support because parameters regulated by S-nitrosylation including blood flow, inflammatory response, and cell signalling are all impacted by BD. And we have determined that SNO activity is impaired following BD. Furthermore, we have preliminary evidence that, after BD, restoration of SNOs preserves organ status. Maintenance of a normal level of SNO activity thus provides an attractive drug target to improve donor status. However, to support conducting such a clinical trial in human donors it is important to first characterize the disruptions in S-nitrosylation in conjunction with the systemic physiologic impairments that occur following BD and during donor support.

Completion of the current study will produce exciting new insights on the key roles of SNOs in regulating donor status and form the basis for a follow-on clinical trial testing if a drug that can increase the amount of SNOs in the body can increase the number and quality of transplantable organ.

Progress Report