FOEDRC announces new pilot grant recipients

The Fraternal Order of Eagles Diabetes Research Center released the following announcement today.

The Fraternal Order of Eagles Diabetes Research Center is pleased to announce the results of its thirteenth round of Pilot and Feasibility 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.

Over a dozen researchers from across the UI campus submitted meritorious proposals that underwent a comprehensive and competitive two-stage review. Two applicants were selected to receive a catalyst award grant of $50,000 to support their research proposal, with the possibility for a second year of funding, for a total of $100,000 over a two-year period. Two applicants were selected to receive one-year seed grant awards of $5,000 each to support discreet research proposals to obtain data needed to generate essential preliminary data in a diabetes-related project to increase competitiveness for subsequent extramural funding.

Catalyst Award Recipients

Brian O’Neill, MD, PhD
Associate Professor of Internal Medicine-Endocrinology and Metabolism

Project: Role of Lrrc2 in the muscle mitochondrial adaptations to diabetes

Uncontrolled diabetes decreases energy production in mitochondria, the cellular powerhouses, which can decrease muscle strength leading to poor recovery from illness or surgery. Our previous work showed that a mouse model of Type 1 diabetes, called STZ diabetes, causes mitochondrial problems in muscle and increases Lrrc2, a protein that localizes to mitochondria and may help increase energy production in the diabetic state. The goal of this project is to see if Lrrc2 is a beneficial factor for mitochondrial function in diabetes. In aim 1, we will test whether increased Lrrc2 expression improves mitochondria and strength in diabetic muscle. Aim 2 will determine which other proteins interact with Lrrc2 in normal and diabetic muscle. These studies on Lrrc2 will help us better understand the connections between diabetes, mitochondria, and muscle weakness that contributes to disability.

Thorsten Maretzky, PhD
Assistant Professor of Internal Medicine-Infectious Diseases

Project: Novel functions of the inactive rhomboid protein 2 in diet-induced obesity

In obesity, white adipose tissue (WAT) undergoes significant changes, impacting metabolic health. These changes include hypertrophy (enlarged adipocytes) and protective hyperplasia (increased adipocyte number). We focus on understanding this balance and the role of iRhom2, an inactive Rhomboid protein known for regulating cell surface molecules related to inflammation and cell growth. Our preliminary findings highlight the impact of iRhom2 and its substrates on adipose tissue responses during excess energy. Using conditional knockout mouse models, we study this pathway in various adipose tissue cell types. Our goal is to uncover the intricate mechanisms driving WAT remodeling in obesity, offering insights into potential metabolic disorder therapies.

Seed Grant Recipients

Sukirth M. Ganesan, BDS, PhD
Assistant Professor, Department of Periodontics, College of Dentistry

Project: Determining the Role of Perfluoroalkyl Substances (PFAS) in the Oral Environment of Children with Obesity and Metabolic Syndrome

Evidence is rapidly accumulating for the worldwide environmental contamination of air and water by Perfluroalkyl substances (PFAS), a class of synthetic chemicals, also known as ‘Forever Chemicals’ leading to widespread human exposure such that, in many developed countries, nearly all individuals have detectable PFAS in their blood. Emerging evidence link PFAS exposure to a wide range of adverse health effects including insulin resistance and diabetes, altered glucose homeostasis, and obesity in adolescents and children. While plasma and serum metabolome are being actively investigated for PFAS exposure, such investigations in saliva are yet to be performed. Results from the validated targeted metabolomics approach will enable us to identify potential associations between PFAS levels in saliva and childhood MetS and Obesity”.

Gourav Bhardwaj, MSc, PhD
Research Assistant Professor, Internal Medicine-Endocrinology and Metabolism

Project: Generation of a cardiomyocyte-restricted inducible striated muscle-enriched protein kinase (Speg) overexpression mouse model to determine the role FoxO3-Speg axis in Diabetic Cardiomyopathy

Patients with diabetes are at a high risk of developing heart failure with preserved ejection fraction (HFpEF), an emerging epidemic without effective treatment strategies. Diastolic abnormalities and calcium (Ca2+) mishandling are the characteristics of diabetic cardiomyopathy (DCM), but the molecular mechanisms of these in context of insulin signaling targets, such as FoxOs, in diabetes are incompletely understood. We show that cardiomyocyte-restricted deletion of FoxO3 (H FoxO3) prevents diastolic dysfunction and Ca2+ abnormalities in Streptozotocin (STZ) diabetic hearts. We also discovered that a Ca2+ regulating protein Speg (striated muscle-enriched protein kinase) was decreased in STZ diabetic hearts, and its expression was restored with the deletion of FoxO3 in STZ H FoxO3 KO. We hypothesized that activation of FoxO3 in diabetic hearts controls Ca2+ flux and heart relaxation via Speg degradation. The support from this seed grant will be used to generate an inducible cardiomyocyte restricted Speg overexpressed mouse model. This new mouse line will be used to determine if increased Speg is sufficient to rescue DCM and to determine the contribution of the FoxO3-Speg axis on Ca2+ flux and diastolic abnormalities. In summary, this study will help determine the role of Speg and FoxO3-Speg axis in diabetic cardiomyopathy and improve our understanding of heart failure progression in patients with diabetes.

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