The National Institute of General Medical Sciences (NIGMS) has awarded Munir Akkaya, MD, DPhil, $1.8 million to understand the factors that regulate cell fate.
An internal medicine researcher and a member of the Division of Rheumatology and Immunology at The Ohio State University College of Medicine, Dr. Akkaya studies B cell biology. The NIGMS grant is a Maximizing Investigators’ Research Award R35 grant that will fund the Akkaya lab’s work for the next five years. The goal of the R35 grant is to give researchers stability and flexibility that enhance their scientific productivity and the chances for important breakthroughs.
Dr. Akkaya wants to understand the cellular processes that activate cells.
Uncovering what happens inside the ‘black box’
An antigen, bacteria or some microbial stimulus from an ongoing infection can elicit a B cell response.
Such stimuli can wake up an immune cell but won’t cause a full-body immune response.
“The body uses checks and balances to make sure the response is appropriate for the stimulus and not geared toward self-destruction or self-harm,” Dr. Akkaya says.
Other stimulations may also come into play. Somehow, the body decides whether to launch an immune response, to ignore the stimulus or to destroy the cell that has become activated.
“I want to understand the machinery inside the cell,” Dr. Akkaya says.
When stimuli encounter a cell, they trigger some sort of signaling followed by a chain of ion transfers. Dr. Akkaya describes it this way: At the end of the signaling pathway is a black box. All the stimuli go into the black box and a result comes out. That result is the fate decision.
His research is all about understanding how a cell makes the decision to survive or die.
Identifying the molecular mechanics at play
“We believe that if we figure out the pattern that controls this system, we may have a better understanding of how autoimmune conditions work,” Dr. Akkaya says.
To find answers, Dr. Akkaya and his team will first work to understand how the cell fate process occurs in a normal healthy cell. Then researchers can relate their findings to autoimmune disease conditions to see if it provides a clearer view of the biological processes at work.
Identifying the molecular mechanisms responsible for these changes can be a stepping stone toward developing therapies that target specific parts of the cell fate pathway that are malfunctioning.
Benefits of a collaborative environment
As the Akkaya lab begins its work on this project, it does have a bit of a head start. The team has completed preliminary studies that show some of the pathways that turn on when stimuli are present.
The major goal of the R35 NIGMS grant is to gain an understanding of what makes the cells behave as they should or exaggerates their behavior in some way.
Once that goal is achieved, the lab will focus on testing disease models for the signaling pathways with in vivo animal models. Ultimately, they hope to advance organism studies to comparative studies in human tissue.
Being part of The Ohio State University Wexner Medical Center provides benefits for his work, Dr. Akkaya says. The collaborative environment and access to many biobanks provide the opportunity for Dr. Akkaya to extend his work to clinical and translational settings.
“It is a big advantage,” Dr. Akkaya says. “We come together on multiple occasions to meet and work together on different endeavors.”
Many options for ongoing studies
The team-based culture inspires Dr. Akkaya to plan to expand his project into studies focused on oncology. In the future, he hopes to have the chance to see if his basic ideas apply to cell fate pathways in patients with leukemia.
The NIGMS grant is renewable after five years, based on progress made and new questions that need to be answered.
“I think if we find a target and what is responsible for the changes we see and the different outcomes we observe, we will have more work to do,” Dr. Akkaya says.
One possible research topic could be exploring why some B cells remain in limbo. This is a gray area that scientists don’t yet understand. Some B cells may stay alive after activation, but in a less functional way.
These cells could be responsible for some type of immune activity, or the body may retain them for some nonfunctional purpose.