Luke Norton, Ph.D.

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