David Al-Adra, MD, PhD

2024 John Merrill Grant in Transplantation

Institution: University of Wisconsin

Project Title: Delivery of a Novel Immune Inhibitory Transgene to Kidneys During Normothermic Preservation to Decrease Rejection After Transplantation

How would you sum up your overall research focus in one sentence?

Investigating novel methods to decrease rejection after transplantation without traditional immunosuppression.

Provide a brief overview of the research you will conduct with help from the grant.

Our approach to decrease rejection after kidney transplantation is through the modification of cells within the organ to express an immune-inhibitory protein that regulates the immune response. We have recently developed an innovative fusion protein: PIDO—which combines the immune-inhibitory properties of the proteins programmed death ligand-1 and indoleamine 2,3-dioxygenase—and have shown the protein's effectiveness at ameliorating islet transplant rejection.

What inspired you to focus your research in this area?

One of the biggest risks of kidney graft loss after transplantation is rejection and drugs that reduce the immune response are taken by the recipient. However, these drugs have significant side effects, including increased risks for infection and cancer formation, and despite their administration, transplant rejection still occurs. I believe we can do better.

What impact do you hope your research will have on patients?

Decrease reliance on immunosuppression.

What are your career goals at the end of the grant period? Five years out? Ten years out?

By the end of this grant period, we will have a vastly improved understanding of how combined PD-L1 and IDO immune-inhibitory pathways can be leveraged to decrease kidney transplant rejection. We will use the results of this research as preliminary data for an R01 application where the aims will be to establish the safety and efficacy of PIDO-based therapeutic strategies in large animal models and to improve the precision of therapeutic delivery to modify distinct cells within the kidney.

In one sentence, please describe the importance of having grant funding available through KidneyCure.

This grant will allow high quality research to be conducted into this novel method of decreasing rejection. Without this award, this research could not be done.

What advice would you give to others to encourage them to apply for this grant funding?

Keep trying!!!