The need for better options in diabetes care inspires Kyle Knofczynski, a student in the Regenerative Sciences Ph.D. track at the Mayo Clinic Graduate School of Biomedical Sciences. Standard insulin replacement therapy has been a lifeline for many people with diabetes, but it doesn't always sufficiently control blood glucose (sugar).  So Knofczynski dared to dream big, setting a goal of advancing a new treatment or even a cure for Type 1 diabetes. Guiding his research journey is his mentor, Quinn Peterson, Ph.D., director of Mayo Clinic's Islet Engineering and Replacement Laboratory. Dr. Peterson is leading research into a cell replacement therapy that could restore the body's insulin-making abilities, potentially eliminating the need for routine blood checks, insulin pumps and glucose monitoring.

"The goal of our research is to offer a functional replacement to pancreatic islet cells that can control blood glucose levels just like the normal pancreas does," says Knofczynski. "Instead of injecting insulin via a pen or an insulin pump, we propose to treat diabetes at the root of the cause. By replacing the damaged pancreatic islets, we hope to restore the body’s ability to respond to blood glucose levels on its own, creating and secreting its own insulin like the native pancreas should."

Central to this research is engineering different cell types known as islets and returning them to the patient. Islets are clusters of cells in the pancreas that produce hormones capable of making and regulating insulin. Insulin helps blood sugar enter the body's cells so it can be used for energy.

Knofczynski's role in this research is to investigate a molecule called transthyretin, which is present in much smaller quantities in people with Type 1 diabetes. He is testing his hypothesis that transthyretin plays an important role in the development and function of islet cells.

"Kyle Knofczynski is working on a project that is aimed at understanding how cells of the islet communicate with each other," says Dr. Peterson, who is also the associate program director for Mayo Clinic's Regenerative Sciences Ph.D. track. "He is focused on a largely overlooked molecule called transthyretin that we hypothesize plays an important role in conversation between the cells. Answering this question will help us build and transplant islet cells that function with more sophisticated precision.”

Working to discover the next cure

Student researchers like Knofczynski who are in the Regenerative Sciences Ph. D. track work side-by-side with established scientists with the aim of finding a cure for some of the world's most complex medical conditions.

Regenerative sciences is an emerging field focused on turning cells and other substances from the body into new drugs. It takes a specially-trained workforce to bring these promising new medicines to patients. However, the field is so new that few books, courses or tools exist to teach physicians and scientists how to deliver biologically based healing agents.

Mayo Clinic is a pioneer in developing regenerative sciences curricula to train future physicians, scientists and support staff. Led by Mayo Clinic's Center for Regenerative Biotherapeutics, regenerative sciences curricula are being integrated into all schools in the Mayo Clinic College of Medicine and Science.

Addressing a chronic disease that affects millions

Type 1 diabetes is a disease that causes the immune system to attack and destroy pancreatic islet cells that produce insulin, a hormone that regulates blood glucose. Severe health complications can occur when the body doesn't make its own insulin. Without insulin, a person's blood glucose can spike, but too much insulin can lead to low blood sugar. In both cases, the complications can be deadly.

Despite advancements in research, standard insulin replacement therapy has not changed in the past century. It is still a 24-hour job for a person to monitor their blood glucose levels and adjust their insulin doses accordingly.  

"Even though insulin injections offer a great way for people to manage blood glucose, there are still a ton of diabetes-related health impacts that can occur such as neuropathy, blindness or kidney failure," says Knofczynski. "Over the years, automation has provided better ways to measure changes in blood glucose and insulin levels, but that still doesn't provide a cure."

The need for new treatment options is great considering 1.9 million people in the U.S. have been diagnosed with Type 1 diabetes, according to the American Diabetes Association.

"When engineered pancreatic islets are fully understood, I think it could potentially be the most groundbreaking advancement in the treatment of diabetes since the discovery and production of insulin itself," says Knofczynski. "However, there is a ton of research that still needs to be done. I am happy to be working on such an important project."

Attracted to an education-research-practice collaboration

Knofczynski says he was drawn to the Mayo Clinic Graduate School of Biomedical Sciences and the Regenerative Sciences Ph.D. track by the relationship between the research, education and practice shields at Mayo.

"Mayo offers so many resources that other institutions might not be able to provide. I have had so much guidance from my mentor and many others. I have the opportunity to learn at a world-class institution and have access to a world-class hospital next door," says Knofczynski. "This has already had an impact on some research where we hope to utilize patient samples to better understand diabetes, something that might be extremely difficult to do elsewhere."

Mayo Clinic established the Regenerative Sciences Ph.D. track in the Mayo Clinic Graduate School of Biomedical Sciences in 2020 to train physicians and scientists to advance a new era of regenerative biotherapeutics. Experts in regenerative sciences teach the courses. The curriculum goes beyond hands-on research to include fundamental cellular and molecular science principles, regulatory issues, quality control, bio-business and entrepreneurial pathways, data science, medical sciences, ethics and emerging technologies.

Knofczynski is in his second year of his doctoral studies. He hopes to graduate with his Ph.D. in 2027.

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