Congratulations to our Bridge to the Cure new recipient!
We are pleased to announce that Dr. Bing Li was selected as a new recipient of the Bridge to the Cure award. Dr. Li will join current recipients of this Award: Dr Julien Sebag and Dr. Calvin Carter.
The Bridge to a Cure initiative is designed to support members of the FOEDRC to accelerate promising research aimed at the development of novel therapeutic approaches for the treatment and/or prevention of diabetes. The support has been made possible by an ongoing commitment of the Fraternal Order of Eagles (FOE) to support the mission of the FOEDRC.
The FOEDRC has assembled an external advisory committee that is tasked with reviewing the proposed projects. This committee is also involved in assessing progress, providing intellectual support and guidance towards meeting expected milestones and with making a recommendation to the F.O.E. foundation regarding future funding of each project.
Funded applicants are expected to provide bi-annual written progress reports and oral presentations to the advisory board and UIRF. Intellectual property arising from work funded will be subject to University of Iowa stipulations.
Bing Li, PhD
Professor, Department of Pathology
Project: Targeting A-FABP with humanized anti-A-FABP monoclonal antibodies for treatment of diabetes
The epidemic of obesity we witnessed over the last few decades is mostly caused by overnutrition. Excess energy stored in adipose tissues leads to fat accumulation, chronic inflammation and multiple obesity-related diseases, including diabetes. Multiple molecular mechanisms linking obesity/diabetes have been proposed, including adipose fatty acid binding protein (A-FABP, also known as FABP4) which has emerged as a new adipokine that promote diabetes development by supporting the production of glucose in the liver and impairing the function of insulin-secreting cells in the pancreas. Thus, targeting A-FABP represents a novel strategy for diabetes treatment. To inhibit AFABP activity, Dr. Bing Li’s group has developed the first humanized anti-A-FABP antibodies, which showed efficacy in lowing glucose levels and increasing insulin sensitivity in preliminary studies. Through the Bridge to the Cure Initiative, Dr. Li’s group will further develop the antibodies and test their therapeutic efficacy using different diabetic animal models. Completion of the project will greatly enhance the commercialization potential of this new treatment for diabetes and other obesity associated diseases.
Recap of 2022 Research Day
The Fraternal Order of Eagles Diabetes Research Center held its 8th annual retreat on December 3, 2022, at the Terry Trueblood Recreation Center. DRC faculty and senior trainees came together for a day of research and celebration of the Center’s continued success.
The day began with opening remarks by Co-Directors’ Kamal Rahmouni, PhD and Andrew Norris, MD, PhD followed by updates from the Metabolic Phenotyping Core and the Metabolomics Core Facility. We also heard from two new DRC faculty members, Bing Li, PhD, and Marcelo Correia, MD. This year we listened to presentations reporting annual progress from last year’s Pilot and Feasibility Grant Recipients, Katie Larson Ode, MD, Jon Resch, PhD, Ling Yang, PhD and Erin Talbert, PhD.
Our keynote speaker was Lori Sussel, PhD from the Anschutz School of Medicine at the University of Colorado’s Barbara Davis Diabetes Center for Diabetes, who gave a talk titled “Pancreatic Islet Function: The Splice of Life”. Dr. Sussel discussed her most recent work regarding the genetic mechanisms that controls the development and function of the pancreas.
For this year’s retreat, we invited the Center for Gene Therapy to join us as many members of this Center are involved in diabetes research. Thus, following the lunch session, the Center for Gene Therapy gave two different presentations. John Engelhardt, PhD, and Amy Ryan, PhD gave talks discussing cystic fibrosis and its relation to diabetes. During the last oral presentation session, we heard updates from first-year T32 Diabetes Research Training Program trainees on their most current research. Other trainees presented their work in a poster format during the lunch session.
Our celebration of yet another successful year for the Diabetes Research Center culminated in the announcement of the trainee prizes bestowed on Paul Williams, PhD and Guorui Deng, PhD.
Pilot and Feasibility Grant Award Recipients Announced
We recently announced the results of the Fraternal Order of Eagles Diabetes Research Center twelfth round of pilot and feasibility research grants. These grant awards fund innovative pilot projects by early career investigators who are entering the diabetes research field, or established investigators with innovative ideas that focus on a new direction in diabetes research. The goal of the program is to generate data that will enable awardees to compete for peer-reviewed national funding for projects that show exceptional promise. A total of 13 researchers from across the University of Iowa campus submitted meritorious proposals that underwent a comprehensive and competitive review.
Two applicants were selected to receive a catalyst award grant to support their research proposal. One of the recipients of this grant is Dr. Anna Stanhewicz who is interested in figuring out why women who develop gestational diabetes during pregnancy are at high risk of developing cardiovascular disease and type 2 diabetes in the decade after pregnancy, even if they are otherwise healthy. The other recipient, Dr. Samuel Stephens, will use animal models and pancreatic human cells to better understand how metabolism supplies antioxidants to the insulin production machinery in the pancreas and more importantly, how this process is lost in the development of type 2 diabetes.
One applicant, Dr. Ling Wang, was selected to receive a one-year seed grant award to support a discreet research proposal to generate essential preliminary data in a diabetes-related project to increase competitive for subsequent extramural funding. Dr. Wang will study the causes underlying impaired diabetic bone healing which may identify novel molecules that can be used for therapy.
Finally, one project spearheaded by Dr. Ashutosh Mangalam in collaboration with the University of Minnesota was selected for funding for one year, with the possibility for a second year. This project focuses on understanding the synergistic environmental factors to predispose and/or exacerbate inflammation and obesity. We are hopeful that findings from these various projects will lay the groundwork for the development of novel strategies to reduce the burden of diabetes and obesity on individuals and society.
Dr. Yorek is chasing down diabetic neuropathy
Neuropathy is a devastating diabetes complication that causes nerve damage throughout the body. This can lead to infection and/or amputation of the affected area. The most common type of neuropathy is peripheral neuropathy. This affects the nerves in the hands, feet, legs, and arms. Peripheral neuropathy is the most common complication of diabetes affecting about 50% of patients. Because early diagnosis is difficult, there is no effective treatment, as the neuropathy can only be detected after the nerve damage is already occurred. Thus, there is a need for a screening method for early detection of diabetic peripheral neuropathy. Early detection would need to be coupled to effective therapies to slow the progression of neuropathy. Unfortunately, such therapies do not yet exist.
FOEDRC faculty member Mark Yorek, PhD, is making significant progress in creating better early detection and treatment of diabetic neuropathy. He and his team have recently published findings that the nerves of the cornea (the outer part of the eye) experience diabetic nerve damage before other parts of the body. Thus, testing the nerves of the cornea might provide a means for early detection of diabetic neuropathy. His group have also recently published practical methods to detect corneal nerve damage in animals and are now working to translate the detection methods to humans.
In a complementary line of research, Dr. Yorek and his laboratory have found that fish oil protects against diabetic neuropathy in rodents. This finding is the culmination of several years of research and has resulted in several recent breakthrough publications. As a result of these advances, his group has now partnered with a pharmaceutical company and the University of Michigan to begin a clinical trial in humans to test the ability of fish oil to protect against diabetic neuropathy in patients with diabetes. These are very exciting developments that we hope will lead to better detection and treatment of this devastating complication of diabetes.
Type 2 diabetes which is closely linked to obesity is a major cause of death due to the many associated illnesses including heart disease. However, our understanding of the biological processes and factors that links type 2 diabetes to obesity and heart disease is limited. FOEDRC faculty Dr. Ling Yang’s research program is aimed at filling this major gap in knowledge. Recently, Dr. Yang was bestowed 2 major awards totaling more than $2.5 million to support her research program. One award was granted to her by the American Heart Association so she can study the communication that takes place between the liver and heart. We know from previous research that the heart requires a significant amount of fat-based fuels to work properly. These good fats are partially provided by the liver through a process that involve a molecule called IRE1. Dr. Yang and her colleagues discovered that when the liver does not have a functional IRE1, it is unable to supply fats to other organs including the heart. The new award will allow her laboratory to decipher how this process works, and to decode whether its perturbation damages the heart. The second award was granted to Dr. Yang by the National Institutes of Health. This project focuses on understanding the function of brown adipose tissue, a special type of body fat that can shed excess calories in the form of heat. Previous work has established that obesity is associated with reduction in brown fat activity and that stimulation of this fat protects against the deleterious effects of obesity and diabetes. Dr. Yang’s research aims to understand how this special fat losses its beneficial activity in obesity. Her laboratory identified a lower level of a protein called ADH5 as a potential culprit in obesity-associated reduction in brown fat activity. The new award will allow Dr. Ling to understand what drives the reduction in ADH5 levels. She also plans to test whether restoring ADH5 function in brown fat can rescue obesity and type 2 diabetes. Thus, the support afforded by the two new awards will allow Dr. Ling and her team to gain important knowledge which can pave the way for the development of new therapies and reduce the burdens of obesity and diabetes
Hybrid Closed-Loop Insulin Pumps Might Protect Childhood Brain Development from the Adverse Effects of Type 1 Diabetes
Over the past decade, evidence has emerged indicating that high blood sugars intype 1 diabetes cause adverse brain changes in children. The adverse changes include abnormal brain structural alterations and reduced functioning on some cognitive tests. Over the past few years, hybrid closed-loop insulin pumps have become commercially available. These devices combine a continuous glucose monitor (CGM) with an insulin pump that is controlled by an algorithm that uses the CGM data to inform insulin delivery. The hybrid closed-loop insulin pumps aim to keep blood sugar in the low 100s (mg/dL). These systems can often improve average blood sugars and reduce the severity and frequency of low and high blood sugars. It is thus natural to ask whether the improved blood sugar control offered by a hybrid closed-loop insulin pumps might reduce the adverse brain effects of type 1 diabetes in children. FOEDRC faculty Dr. Mike Tansey and Dr. Eva Tsalikian were among a small group of diabetes physicians across the United States who designed such a study to answer this very question. The initial results from the study were just published in the prestigious journal Nature Communications. Their randomized clinical study involved 42 adolescents with type 1 diabetes who were randomized to a hybrid closed-loop insulin pump versus conventional therapy. They were studied 6 months later, undergoing a brain MRI and cognitive testing. Although this study was considered a pilot trial, the results showed significantly less adverse impacts in those randomized to the hybrid closed-loop insulin pumps. The hybrid closed-loop insulin pump group performed better on a cognitive test of perceptual reasoning and had fewer abnormal structural brain changes. These results add to the growing evidence showing that excessive hyperglycemia is damaging to the developing brain during childhood. This study shows the important positive impact that hybrid closed-loop insulin pumps can make in improving blood sugar levels and long-term outcomes in children with diabetes.