It’s a Dutch hat trick: College of Health Professor gets three subsidy notifications in one day

01 Aug 2022 17:00 hrs

Author:
Doug Dollemore

William Holland, PhD
William Holland, PhD, associate professor of Nutrition and Integrative Physiology, recently received three grant applications in one day. Photo credit: Charlie Ehlert

Imagine a cure for diabetes – a disease that affects one in ten Americans. It may not happen in our lifetime, but the work of William Holland, PhD, an associate professor in the Department of Nutrition & Integrative Physiology at the University of Utah Health, brings us closer. Major institutions are taking note, and the Netherlands recently delivered a rare feat in the world of academic research: three award notifications in one day.

Reduced Diabetes Complications

The first is a renewal of funding from the National Institute of Diabetes and Digestive and Kidney Diseases, through the National Institutes of Health. The $1,820,000 grant over the next four years will support the Netherlands’ efforts to explore how to reverse type 1 diabetes.

While an assistant professor at the University of Texas Southwestern Medical Center, Holland helped discover that blocking a glucagon receptor in a type 1 diabetic animal was curative — one injection in mice was enough to completely cure them of diabetes. The insulin-producing beta cells grew back so quickly that the mice needed no further treatment.

In the future, the Netherlands will try to determine how this is done so that it can be safely translated into the treatment of diabetes in humans, while avoiding difficult side effects such as liver toxicity and hypertension.

“If you can get a fraction more insulin-producing beta cells to a patient, that will significantly reduce many of the complications of diabetes,” Holland said. “If their insulin production works, it helps prevent hypoglycemic episodes, neuropathy, vascular disease, heart disease, and so on. Very few people die of diabetes; they die from complications of diabetes.”

A genius way to predict disease vulnerability

The second grant is from the American Diabetes Association for $200,000 per year for three years. It will enable the Netherlands to continue to explore how genetics can be used to provide precision therapies for individuals suffering from diabetes and heart disease.

Hyperceramideemia means that your blood contains too many lipids called ceramides. Research into the condition includes genetic sequencing to determine which genes regulate these toxic lipids that predict diabetes and heart disease.

Building on a collaboration with a colleague from the University of Wisconsin, Holland is studying human genetic data from multiple generations of volunteers at the University of Utah. The collaboration with Wisconsin showed that small pieces of DNA can be used to identify ceramide levels based on a specific gene segment.

Today, the Dutch team is measuring the ceramides and genetic sequencing of patients prone to disease. They are examining the genes identified in a mouse to see if they correlate with disease and toxic lipid levels in humans.

“One of the things you can take from this is the ability to genotype a person to determine their risk of diabetes or heart disease in childhood,” Holland said. “If so, we can intervene to make sure this never becomes a problem, such as avoiding a diet high in saturated fat.”

During this research, Holland identified what he believes is the first case of “familiar hyperceramidemia,” a family in which 64% of members are on dialysis. This family has a mutation in adiponectin, which means they have a lesion in the gene that causes high levels of ceramide in their bloodstream.

The Dutch team continues to investigate whether this genetic lesion leads to a high risk of diabetic kidney disease. The study of these rare genetic cases could help determine the drugs that could be helpful for a whole group of people predisposed to diabetes.

Small Steps Towards a Big Cure

Finally, the Netherlands received a two-year research award notification from SymbioCellTech, LLC. With this grant, he is funding his lab’s research into transplanting and evaluating human neo-islets.

Islets are clusters of insulin-producing beta cells. When transplanted, they can release insulin to control blood glucose. SymbioCellTech is a Utah-based biotechnology company working to cure diabetes through a patented stem cell therapy involving neoislets.

This research will specifically benefit patients who have had transplants – a specific immune rejection that causes type 1 diabetes also predisposes transplanted islets to immune destruction. Holland’s collaboration with SymbioCellTech aims to help overcome this barrier to treatment.

Perhaps most impressively, Holland is the principal investigator of all three grants that have received more than $2.7 million in total. He received a PhD in biochemistry from the University of Utah and completed his graduate research with Scott Summers, PhD, the current chair of the Division of Nutrition & Integrative Physiology. Like Summers, Holland is motivated to cure diabetes because of a history of the disease in his family: his mother and grandfather both had serious complications.

“My goal is to change the limitations around diabetes detection and treatment,” Holland said. “I know how long everything will take, so my goal is to change the future of my children and nieces so that they grow up with more health and less medicine.

Written by Sarah Shebek

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