Roberta Leonardi, PhD

Associate Professor

Organization:

West Virginia University School of Medicine

Department:

Biochemistry and Molecular Medicine

Classification:

Faculty

Selected Peer-Reviewed Articles:

1. Saporito DC, King RD, Vickers SD, Wyda EA, Balaji S, Kolandaivelu S, et al. Loss of the CoA-degrading enzyme NUDT19 exacerbates albuminuria and disrupts renal lipid homeostasis in high fat diet-fed mice. Sci Rep. 2026;16(1):5820. Epub 20260120. doi: 10.1038/s41598-026-36136-7. PubMed PMID: 41559371; PubMed Central PMCID: PMCPMC12894707.

2. Kelley EE, Giromini AP, Maxwell BA, Spears AL, Lewis SE, Salvatore SR, et al. A Regionally Inspired West Virginia Obesogenic Diet Induces Fat Accretion and Metabolic Dysfunction While Identifying Sex Disparity. bioRxiv. 2026. Epub 20260218. doi: 10.64898/2026.02.16.706140. PubMed PMID: 41756906; PubMed Central PMCID: PMCPMC12934774.

3. Cal K, Leyva A, Rodriguez-Duarte J, Ruiz S, Santos L, Garat MP, et al. A nitroalkene derivative of salicylate, SANA, induces creatine-dependent thermogenesis and promotes weight loss. Nat Metab. 2025;7(8):1550-69. Epub 20250617. doi: 10.1038/s42255-025-01311-z. PubMed PMID: 40527924; PubMed Central PMCID: PMCPMC12373507.

4. Giromini AP, Salvatore SR, Maxwell BA, Lewis SE, Gunther MR, Fazzari M, et al. Obesity-Associated Hyperuricemia in Female Mice: A Reevaluation. Gout Urate Cryst Depos Dis. 2024;2(3):252-65. Epub 20240830. doi: 10.3390/gucdd2030019. PubMed PMID: 40124847; PubMed Central PMCID: PMCPMC11928164.

5. Vickers SD, Shumar SA, Saporito DC, Kunovac A, Hathaway QA, Mintmier B, et al. NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet. J Biol Chem. 2023;299(1):102745. Epub 20221124. doi: 10.1016/j.jbc.2022.102745. PubMed PMID: 36436558; PubMed Central PMCID: PMCPMC9792899.

6. Vickers SD, Saporito DC, Leonardi R. Measurement of Fatty Acid beta-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes. J Vis Exp. 2021;(175). Epub 20210909. doi: 10.3791/62904. PubMed PMID: 34570107; PubMed Central PMCID: PMCPMC9035282.

7. Naquet P, Kerr EW, Vickers SD, Leonardi R. Regulation of coenzyme A levels by degradation: the 'Ins and Outs'. Prog Lipid Res. 2020;78:101028. Epub 20200329. doi: 10.1016/j.plipres.2020.101028. PubMed PMID: 32234503; PubMed Central PMCID: PMCPMC7234920.

8. Shumar SA, Kerr EW, Fagone P, Infante AM, Leonardi R. Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver. J Lipid Res. 2019;60(5):1005-19. Epub 20190307. doi: 10.1194/jlr.M092676. PubMed PMID: 30846528; PubMed Central PMCID: PMCPMC6495166.

9. Kerr EW, Shumar SA, Leonardi R. Nudt8 is a novel CoA diphosphohydrolase that resides in the mitochondria. FEBS Lett. 2019;593(11):1133-43. Epub 20190502. doi: 10.1002/1873-3468.13392. PubMed PMID: 31004344; PubMed Central PMCID: PMCPMC6557688.

10. Shumar SA, Kerr EW, Geldenhuys WJ, Montgomery GE, Fagone P, Thirawatananond P, et al. Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform. J Biol Chem. 2018;293(11):4134-48. Epub 20180129. doi: 10.1074/jbc.RA117.001358. PubMed PMID: 29378847; PubMed Central PMCID: PMCPMC5857999.

11. Corbin DR, Rehg JE, Shepherd DL, Stoilov P, Percifield RJ, Horner L, et al. Excess coenzyme A reduces skeletal muscle performance and strength in mice overexpressing human PANK2. Mol Genet Metab. 2017;120(4):350-62. Epub 20170203. doi: 10.1016/j.ymgme.2017.02.001. PubMed PMID: 28189602; PubMed Central PMCID: PMCPMC5382100.

12. Shumar SA, Fagone P, Alfonso-Pecchio A, Gray JT, Rehg JE, Jackowski S, Leonardi R. Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice. PLoS One. 2015;10(6):e0130013. Epub

20150608. doi: 10.1371/journal.pone.0130013. PubMed PMID: 26052948; PubMed Central PMCID: PMCPMC4460045.

13. Jackowski S, Leonardi R. Deregulated coenzyme A, loss of metabolic flexibility and diabetes. Biochem Soc Trans. 2014;42(4):1118-22. doi: 10.1042/BST20140156. PubMed PMID: 25110012; PubMed Central PMCID: PMCPMC4950865.

2014 - Oral communication winner, Coenzyme A and its Derivatives in Cellular metabolism and Disease, Biochemical Society Focused Meeting

Big 12 Faculty Fellowship, West Virginia University, 2018

Chancellor’s Award for Outstanding Achievement in Research, West Virginia University, 2023

Metabolism

Coenzyme A (CoA) is an essential and universally distributed cofactor that lies at the center of cellular metabolism. Free CoA and its acyl-CoA thioesters participate in the oxidation of carbohydrates, fatty acids, ketone bodies, and amino acids, as well as in lipid biosynthesis. In addition, CoA provides the acyl groups required for the post-translational modification (acylation) of histones and thousands of non-histone proteins, linking cellular metabolism to gene expression and protein function.

Intracellular CoA levels are tightly regulated and rapidly adjusted in response to changes in nutrient availability and metabolic state, including fasting, feeding, and diabetes. Disruption of this regulation impairs metabolic homeostasis and contributes to the development of metabolic disease. Despite the physiological importance of CoA regulation, the mechanisms that dynamically control intracellular CoA levels remain incompletely understood.

CoA homeostasis is maintained through the coordinated regulation of synthesis and degradation. While the biosynthetic pathway has been extensively studied, considerably less is known about the mechanisms that regulate CoA degradation and how they contribute to the control of intracellular CoA/acyl-CoA pools. Emerging evidence suggests that CoA degradation is spatially organized, with distinct CoA-degrading enzymes exhibiting organ- and organelle-specific localization and regulating specialized CoA-dependent metabolic processes within individual cellular compartments.

Our laboratory investigates how cells regulate CoA levels across biological scales—from enzymes and organelles to tissues and whole-body physiology. We study how currently known CoA-degrading enzymes regulate intracellular CoA/acyl-CoA pools and metabolic function, while also seeking to identify new regulators of CoA homeostasis. Using enzymology, biochemistry, molecular biology, metabolomics, stable-isotope tracing, cell culture, genetically engineered mouse models, and integrative physiology, we investigate CoA metabolism from individual enzymes to whole-body physiology.

Our long-term goal is to define the fundamental principles governing CoA homeostasis and determine how compartment-specific regulation of CoA metabolism influences organ function, metabolic flexibility, and whole-body energy homeostasis. Ultimately, we aim to leverage this knowledge to develop new therapeutic strategies to correct the dysregulated metabolism that underlies metabolic disease.