Scott Krummey, MD, PhD

2024 Carl W. Gottschalk Research Scholar Grant

Institution: Johns Hopkins University

Project Title: Role of CD43 Signaling on Effector CD8+ T Cells in Acute Rejection

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

I am interested in understanding the mechanisms by which T and B cells recognize donor antigen and mediate graft rejection.

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

For kidney transplant patients, acute rejection is a persistent clinical problem that leads to graft loss. The population(s) of effector T cells that recognize the graft and cause tissue damage are poorly understood. My group previously identified a population of CD43+ CD8+ T cells that are potent mediators of acute graft rejection. The work in the grant is to better understand the inflammatory signals that drive the formation of this population and to investigate the function of the CD43 receptor on these cells. We also have several tools to translate this finding into human CD8+ T cells, and we will investigate the function of alloreactive CD43+ CD8+ T cells.

What inspired you to focus your research in this area?

I was motivated by the long-standing nature of the problem of acute rejection. Although acute rejection is treatable, recent data has demonstrated that acute rejection is a significant risk factor for early graft loss. To me, the major limitation in this area of research was the identification of the graft-specific CD8+ T cells, which led us to develop the tools to study graft-specific populations.

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

I hope that our work can lead to new approaches to target allogeneic T cells and limit acute rejection.

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

My goals for the funding period are to significantly advance our understanding of how CD43+ CD8+ T cells form and function in mice and humans. In five years, I would love to translate this work into a biomarker of T cell alloimmunity that could be incorporated into patient care. In 10 years, I hope we have some level of personalized immunosuppression regimens based on the characteristics of the patient immune system.

What has surprised you most about your career?

Everything! I have been fascinated by transplant immunology for over a decade now. Transplantation studies were the basis for many early immunology discoveries, and transplant immunology is still a critically important field. I truly enjoy being able to work on the basic science and clinical side of transplant immunology through the Immunogenetics Laboratory.

What are the major challenges facing nephrology research today?

I can speak to kidney transplantation: the largest challenge is the long-standing and growing organ shortage. There are a number of lines of investigation that are being pursued to address this, but it will probably take multiple advances in order to make significant progress.

Something you may not know about me is…

I am a huge Pittsburgh Penguins fan!

In my free time, I like to…

Spend time with my wife and three boys.