Luke Norton, Ph.D.
Associate Professor (tenure track)
Ph.D. in Integrated Biomedical Sciences
Physiology and Pharmacology
Personal Statement:
I am interested in the discovery of novel molecular, metabolic and physiologic pathways in liver that contribute to the pathophysiology of type 2 diabetes and associated comorbidities such as obesity and non-alcoholic fatty liver disease (NAFLD). Currently my laboratory is interrogating the role that mitochondria play in hepatic insulin resistance, and in how hepatocyte metabolic heterogeneity in liver regulates pathways of lipid metabolism, inflammation and fibrosis in NAFLD and NASH.
Education
Education:
2007 - PhD - Biomedical Science (NA) - University of Nottingham
2003 - BS - Human Physiology (First class honours) - University of Hertfordshire
Appointments:
1/2014 - Assistant Professor/Research - University of Texas Health Science Center at San Antonio, Medicine
4/2010 - Instructor and Other - University of Texas Health Science Center San Antonio (UTHSCSA), Medicine, San Antonio
Instruction & Training:
5/2013 - Present, Ph.D. Dissertations Directed, UTHSCSA
5/2013 - Present, Membership on Supervising Committee, UTHSCSA
Research
Grants
Federal
Funding Agency NIH Title The role of glucose mediated glucose uptake in the pathogenesis of IFG and IGT (NIH R01DK09755401) Status Active Period 9/2012 – 9/2017 Role Co-Investigator Grant Detail Funding Agency NIH/NIA Title K01 Career Development Award Status Active Period 5/2014 – 5/2017 Role Principal Investigator Grant Detail Single-nucleotide polymorphisms (SNP) within the transcription factor 7-like 2 (TCF7L2) gene have been consistently associated with an elevated risk for type 2 diabetes (T2DM) in multiple populations throughout the world, but the mechanisms by which TCF7L2 affects the pathways important for the development of T2DM are still poorly understood. Addressing this question is of major importance, primarily because functional investigations into T2DM candidate genes will reveal novel molecular pathways that affect important physiological processes that are highly disturbed in T2DM. In several human studies, carriers of the T-allele for the “at-risk” SNP (rs7903146) have impaired hepatic glucose production (HGP) and hepatic insulin sensitivity. Preliminary findings from the laboratory of Dr Norton demonstrating that silencing of TCF7L2 markedly up- regulates HGP in vitro, strongly support a role for TCF7L2 in the pathways of HGP. The aim of this proposal is to establish the functional role of the T2DM candidate gene TCF7L2 in HGP in vivo, and to investigate the molecular mechanisms by which TCF7L2 affects the pathways of glucose metabolism in the liver. A combination of integrative physiology and genomics approaches will be used to address the central hypothesis that TCF7L2 is a major regulator of HGP in vivo and that transcriptional control of key metabolic genes by TCF7L2 in the liver is the underlying mechanism of this regulation. The major training component of this proposal is the acquisition, refinement and application of new skills, with focus on two areas: (i) integrated physiology, and (ii) functional genomics and bioinformatics. These thematic areas were selected because at the present time knowledge about these areas is extremely valuable to conduct cutting-edge diabetes research, and these areas are cohesive and highly integrated with the scientific goals of this project. In addition, the scientific objectives of this proposal will be coupled with an intensive c
Private
Funding Agency Metabolic Solutions Devlopment Agency Title Efficacy and mechanism of action of anti-diabetic drug MSDC-0602 Status Active Period 2/2013 – Present Role Co-Investigator Grant Detail Funding Agency Title Sodium Coupled Glucose Transporter (SGLT) Expression in the Human Diabetic Kidney Status Active Period 3/2010 – Present Role Co-Principal Investigator Grant Detail
Publications
Shannon, C. E., Bakewell, T., Fourcaudot, M. J., Ayala, I., Smelter, A. A., Hinostroza, E. A., Romero, G., Asmis, M., Freitas Lima, L. C., Wallace, M., & Norton, L. (2024). The mitochondrial pyruvate carrier regulates adipose glucose partitioning in female mice. Molecular Metabolism, 88, 102005. https://doi.org/10.1016/j.molmet.2024.102005
Biju, K., Hernandez, E. T., Stallings, A. M., Felix-Ortiz, A. C., Hebbale, S. K., Norton, L., Mader, M. J., & Clark, R. A. (2024). Resistance to high-fat diet-induced weight gain in transgenic mice overexpressing human wild-type α-synuclein: A model for metabolic dysfunction in Parkinson’s disease. Research Square, rs.3.rs-4870881. https://doi.org/10.21203/rs.3.rs-4870881/v1
BENJAMIN LI, ARUSHI VARSHNEY, ADELAIDE TOVAR, NANDINI MANICKAM, PETER ORCHARD, RALPH A. DEFRONZO, LUKE NORTON, STEPHEN PARKER; 278-OR: Single-Nucleus Multiomics Profiling across 49 Individuals of Hispanic Ancestry Reveals Cell-Specific Skeletal Muscle Insulin-Responsive Gene Regulatory Signatures. Diabetes 14 June 2024; 73 (Supplement_1): 278–OR. https://doi.org/10.2337/db24-278-OR
Shannon, C. E., Bakewell, T., Fourcaudot, M. J., Ayala, I., Romero, G., Asmis, M., Freitas Lima, L. C., Wallace, M., & Norton, L. (2024). Sex-dependent adipose glucose partitioning by the mitochondrial pyruvate carrier. BioRxiv, 2024.05.11.593540. https://doi.org/10.1101/2024.05.11.593540
Brown M, Moody A, Vasquez J, Blangero J, Norton L, Clarke G. 478 Magnetic Resonance Biomarkers of Metabolic Dysfunction-Associated Steatotic Liver Disease. Journal of Clinical and Translational Science. 2024;8(s1):141-141. doi:10.1017/cts.2024.405