Orhan Efe, MD

2022 KidneyCure Research Fellowship Award

Institution: Massachusetts General Hospital

Project Title: Selective Regulatory T Cell Expansion by A Novel IL-2 Mutein as a Glucocorticoid Minimizing Strategy in Glomerulonephritis

How would you sum up your research in one sentence?

We will investigate the efficacy of regulatory T cell expansion by a novel IL-2 mutein in the treatment of crescentic glomerulonephritis to minimize the steroid use.

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

Glucocorticoids (GCs) are part of the standard of care for glomerulonephritis (GN) treatment despite their detrimental off-target effects such as infections and hyperglycemia. Alternative approaches are critically needed to avoid these toxicities. Regulatory T cells (Tregs) are key elements of the regulatory immune system, and they can suppress both adaptive and innate immune system. Hence, expansion of Tregs can be a wise strategy to minimize GC use in GN. We designed a novel IL-2 mutein (mIL-2) which selectively expands Tregs. We will examine the efficacy of mIL-2 alone or in combination with low dose GCs in a murine model of crescentic GN. To investigate the risk of infection associated with mIL-2 in comparison to steroids, we will use a murine infection model as well.

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

At the end of the grant period, my goal is to test my hypothesis, enhance my research skills, and report our results to scientific and patient community. These will lead me to take one more step towards being an independent investigator.

In the long term, I aim to investigate the efficacy of Treg expanding strategies in various glomerulonephritis and transplantation models and focus on their clinical implementation. In addition, I plan to study induction of antigen-specific tolerance to achieve patient specific and more targeted therapies. These will steer me to become an independent clinician-investigator in the field of my interests. While enduring my research activities, I will continue to excel in the patient care and promote medical education. Thus, I will set up my academic future on the tripod of research, strong clinical practice, and medical education.

What inspired you to focus your research in this area?

First, I was inspired to conduct basic and translational research by former mentors Drs. Jeff Sands and Janet Klein prior to my residency. During my first year of fellowship, I was captivated by the patients with glomerulonephritis and kidney transplantation. Witnessing the numerous toxicities of conventional immunosuppression, I have developed a genuine interest in novel therapies to avoid these toxicities. With the encouragement of my excellent mentor Dr. Leonardo Riella, I started to study expansion of regulatory T cells in the treatment of autoimmune diseases and transplantation models.

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

Writing a grant application itself is an amazing experience and an important step for a researcher's development. It would a unique experience to produce a new hypothesis and test it in a scientific project. This would lead to development of a scientific mindset and a clinician with scientific perspectives. Lastly, this grant opportunity would open the doors of a physician-investigator career for young Nephrologists.

Something you may not know about me is…

Soccer is my passion.

In my free time I like to…

Play soccer and spend time with family.

Follow on Twitter: @OrhanEfe_