The Arkansas Integrative Metabolic Research Center will host the year-four pilot project awardee, Leonard Harris, and lab members Lauren Van Dee of the Girodat/Thallapuranam labs and Oscar Vicen of Rosa-Caldwell lab, at 10:45 a.m. Wednesday, Sept. 3, in BELL 2267.

In this talk, they will discuss the results of their research. Three projects will be discussed:

Mutations in Fanconi Anemia

Project Title: Investigating the impact of mutations in Fanconi anemia-related genes on mitochondrial function and cellular metabolism using a Seahorse analysis approach (Leonard Harris – pilot project leader)

Abstract: Fanconi anemia (FA) is a rare genetic disorder characterized by defective DNA repair, mitochondrial dysfunction and increased cancer risk. Using bioenergetics assays, we investigated how FA-associated gene mutations alter oxygen consumption, glycolysis rates and ATP production in FA-deficient, gene-corrected and healthy cells. FA‐deficient cells showed reduced mitochondrial capacity yet produced more total ATP from both oxidative phosphorylation and glycolysis than healthy cells, consistent with elevated energy demand from persistent DNA damage signaling. Gene correction lowered ATP production to near‐healthy levels but shifted the balance toward glycolysis. This likely reflects reduced energy demand as DNA repair capacity is restored, and persistent residual mitochondrial damage accrued before correction. Redox imaging revealed that FA‐deficient cells had higher redox ratios than healthy cells, whereas gene‐corrected cells had lower ratios, mirroring their mitochondrial ATP output. These findings highlight the complex, context‐dependent metabolic behavior of FA cells and the lasting impact of prior mitochondrial injury.

Biography: Leonard Harris, Ph.D., is an assistant professor of biomedical engineering at the University of Arkansas. His research focuses on cancer systems biology, with a specialization in computational modeling of biochemical signaling pathways, cell-cell interactions, and tumor microenvironments. His lab integrates computational models with experimental data to investigate phenotypic plasticity, drug tolerance and metabolic dysfunction in cancer and rare diseases such as FA. Current projects span tumor-induced bone disease, melanoma drug resistance and FA-associated metabolic alterations, combining bioenergetics assays, mRNA expression, advanced imaging and in vivo experiments with multiscale modeling and AI/ML methods. Dr. Harris earned his Ph.D. in chemical and biomolecular engineering from Cornell University and completed postdoctoral training at the University of Pittsburgh and Vanderbilt University School of Medicine. He is a member of the Cancer Biology Program at the Winthrop P. Rockefeller Cancer Institute and collaborates nationally and internationally with both experimentalists and clinicians.

Effects on Diamond-Blackfan Anemia

Project Title: Effects of ribosomal protein haploinsufficiency on metabolism and mTOR activation in Diamond-Blackfan Anemia (Dylan Girodat and Suresh Thallapuranam – pilot project leaders)

Abstract: Diamond-Blackfan Anemia (DBA) is a rare bone marrow failure syndrome. Approximately 60%-70% of DBA cases result from a mutation in a ribosomal protein (RP), resulting in its haploinsufficiency. Although ribosomes are essential for protein synthesis across cell types, DBA manifests as a tissue-specific disease by unknown mechanisms. Metabolic dysregulation has been associated with DBA and is an appealing mechanism by which RP haploinsufficiency could result in erythroid failure. In this pilot project, we model DBA in human cells using RNAi to knock down RP expression. Models show metabolic dysregulation in the form of elevated oxygen consumption rates, alleviated by adding fibroblast growth factors (known mTOR modulators). Our models also exhibit decreased mTOR activation. Additionally, proteomic analysis reveals upregulation in IRES-mediated translation, indicating that haploinsufficiency may lead to "preferentially" translating ribosomes. Our findings indicate that treatment of metabolic dysregulation may be an option for DBA patients, and mTOR modulators may be a possible therapeutic.

Biography: Lauren Van Dee is a third-year Ph.D. student in the lab of Dylan Girodat in the Department of Chemistry and Biochemistry.  She is a Doctoral Academy Fellow at the U of A. She obtained a B.S. in biology and a B.S. in chemistry from the University of Arkansas at Monticello in 2021. In 2023, she graduated from the University of St. Joseph, Connecticut, with an M.S. in biochemistry. Van Dee's dissertation studies focus on how ribosomal protein haploinsufficiency affects metabolism and ribosome function in Diamond-Blackfan Anemia.

Anorexia Nervosa and Muscle Metabolic Health

Project Title: Muscle Metabolic Health During Anorexia Nervosa: An Under-Investigated Moderator of Health and Quality of Life (Dr. Megan Rosa-Caldwell - Pilot Project Leader)

Abstract: Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and relapse rates, yet its physiological underpinnings remain poorly understood. AN is marked by prolonged caloric restriction and reduced body weight and is associated with impaired physiological function. Energy availability and metabolism (EAM2) research addresses a critical gap by investigating skeletal muscle health—a key modulator of metabolism and quality of life—in the context of AN. In this pilot project, we assessed muscle function, metabolic function and biomolecular modulators of muscle health. In this talk, Oscar Vicen will describe preliminary results from this project —transcriptomic and proteomic profiles with physiological measures —to identify key gene expression patterns and biological pathways that drive muscle dysfunction with models of AN. Findings from this study will inform future diagnostic and therapeutic strategies, improving outcomes for individuals with AN.

Biography: Vicen is from Springdale and completed his undergraduate degree at the U of A. He is currently a second-year graduate student in exercise science and has been working with the EAM2 Lab for the past year, where he has found a new interest in research. His academic and professional background centers on muscle physiology, personal training, strength and conditioning; Vicen has CSCS and USA-Weightlifting certification. In addition to research, he has experience as a teaching assistant. He is currently completing his thesis with the EAM2 Lab and plans to continue his education in a doctoral program in exercise science.

More Information

This event is supported by NIGMS of the National Institutes of Health under Award Number P20GM139768. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Please contact Kimberley Fuller, fullerk@uark.edu, for more information.

For those unable to attend in person, this seminar will also be available via Zoom.