Skelton Lab

Skelton Lab Research  
Changes in cellular metabolism have profound effects on brain function. Our lab, led by Matthew R. Skelton, PhD, focuses on the metabolic effects of two disorders: creatine transporter deficiency and bipolar disorder.

Creatine Transporter Deficiency

Discovered at Cincinnati Children’s by Drs. Ton de Grauw and Kim Cecil, creatine transporter deficiency (CTD) is caused by the loss of the creatine transporter gene. Patients with CTD develop an autistic-like phenotype with intellectual disability, significant reductions in language development, ADHD and epilepsy. Unlike similar disorders in which creatine synthesis is impaired, creatine supplementation does not improve the quality of life for these patients. The primary goal of our research in CTD is to better understand how the loss of creatine disrupts brain function, leading to the development of therapies for this currently untreatable disorder.

Bipolar Disorder

Bipolar disorder (BD) is the sixth leading cause of disability worldwide, affecting approximately 3% of the adult population. Currently, the etiology of BD is unknown. Current treatment protocols include antipsychotics and mood stabilizers, such as lithium. However, these treatments have significant side effects, causing additional health problems as well as reducing compliance. A better understanding of brain function in BD is required in order for more effective treatments to be developed. Recent data indicate that mitochondrial respiration is impaired in patients with BD. Our lab focuses on how these changes in mitochondrial function are related to the BD phenotype. 

Contact Us

A photo of Matthew Skelton.

Matthew R. Skelton, PhD
Assistant Professor, UC Department of Pediatrics

Phone: 513-636-8632


Sugimoto, C; Perna, MK; Regan, SL; Tepe, EA; Liou, R; Fritz, AL; Williams, MT; Vorhees, CV; Skelton, MR. A Gad2 specific Slc6a8 deletion recapitulates the contextual and cued freezing deficits seen in Slc6a8-/y mice. Brain Research. 2024; 1825:148690.

Broca-Brisson, L; Harati, R; Disdier, C; Mozner, O; Gaston-Breton, R; Maïza, A; Costa, N; Guyot, AC; Sarkadi, B; Apati, A; et al. Deciphering neuronal deficit and protein profile changes in human brain organoids from patients with creatine transporter deficiency. eLife. 2023; 12:RP88459.

Mabondzo, A; Harati, R; Broca-Brisson, L; Guyot, AC; Costa, N; Cacciante, F; Putignano, E; Baroncelli, L; Skelton, MR; Saab, C; et al. Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency. Frontiers in Molecular Neuroscience. 2023; 16:1118707.

Krikorian, R; Skelton, MR; Summer, SS; Shidler, MD; Sullivan, PG. Blueberry Supplementation in Midlife for Dementia Risk Reduction. Nutrients. 2022; 14:1619.

Hall, CH T; Lee, JS; Murphy, EM; Gerich, ME; Dran, R; Glover, LE; Abdulla, ZI; Skelton, MR; Colgan, SP. Creatine Transporter, Reduced in Colon Tissues From Patients With Inflammatory Bowel Diseases, Regulates Energy Balance in Intestinal Epithelial Cells, Epithelial Integrity, and Barrier Function. Gastroenterology. 2020; 159:984-998.e1.

Miles, KN; Skelton, MR. Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits. Brain Research. 2020; 1734:146697.

Abdulla, ZI; Pennington, JL; Gutierrez, A; Skelton, MR. Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness. Behavioural Brain Research. 2020; 377:112254.

Abdulla, ZI; Pahlevani, B; Lundgren, KH; Pennington, JL; Udobi, KC; Seroogy, KB; Skelton, MR. Deletion of the Creatine Transporter (Slc6a8) in Dopaminergic Neurons Leads to Hyperactivity in Mice. Journal of Molecular Neuroscience. 2020; 70:102-111.

Udobi, KC; Delcimmuto, N; Kokenge, AN; Abdulla, ZI; Perna, MK; Skelton, MR. Deletion of the creatine transporter gene in neonatal, but not adult, mice leads to cognitive deficits. Journal of Inherited Metabolic Disease. 2019; 42:966-974.

Ullio-Gamboa, G; Udobi, KC; Dezard, S; Perna, MK; Miles, KN; Costa, N; Taran, F; Pruvost, A; Benoit, J; Skelton, MR; et al. Dodecyl creatine ester-loaded nanoemulsion as a promising therapy for creatine transporter deficiency. Nanomedicine (London, England). 2019; 14:1579-1593.