Dr. Shaked current studies are focused on human immunological monitoring in the transplant setting.

1. We are using gene expression profiling for the characterization of innate immunity and adaptive immunity pertinent to solid organ transplantation.
   In renal allograft recipients, we will investigating whether: (a) acute rejection can be predicted by sequential mRNA profiling of urinary cells; (b) preemptive treatment, based on mRNA profiles, prevents acute rejection and preserves GFR, and (c) mRNA profiles can be used to guide immunosuppression management, such as the withdrawal of calcineurin inhibitors in stable recipients.

   Studies in diverse groups of transplanted organs are centered on the molecular profiling of organ specific and non-specific injury pathways in the donor prior to procurement and in the recipient immediately after transplantation, and their impact on organ function and alloreactivity.

2. Liver tolerance in the setting of HCV infection:
   It is possible that tolerance induction may be occurring in a significant number of liver transplant recipients already as a result of variables intrinsic to the organ. In these individuals, tolerance was achieved either after abrupt discontinuation of immunosuppression, or following gradual weaning of immunosuppression long after transplantation. Importantly, the occurrence of rejection during weaning was reversed by reinstitution of immunosuppression, and did not result in a significant long-term damage to the graft. The current study is focused on recipients undergoing OLT for CAHC. The aims are to determine whether HCV infected individuals who become tolerant express immune and genetic profiles that are similar to non-HCV infected recipients, and if immunosuppression withdrawal at a later stage has favorable impact on the severity of HCV recurrence and injury to the transplanted graft.

3. Immune response in the setting of Living Donor Liver Transplantation (LDLT):
   LDLT and cadaveric transplantation are associated with differential pathways of inflammatory response and immune activation, resulting in development of a distinct state of tolerance to the allograft.

1. Regeneration may be associated with different pattern of lymphocyte trafficking in and out the graft resulting in a differential repopulation of the liver with donor cells, and unknown effects on the extent of peripheral chimerism.
2. Transplantation of a lobe from a living donor is done under conditions allowing extremely short cold ischemic time, a variable that may affect the severity of the inflammatory and immune response.
   We are investigating whether this phenomenon would be reflected in the frequency of episodes of acute or chronic rejection, and the appearance of peripheral and intragraft molecular and cellular profiles that are indicative of donor-specific alloresponsiveness.