The Rider Lab studies how the AMP-activated protein kinase (AMPK) and insulin/protein kinase B (PKB) signalling pathways control cell function.
Could small-molecule pharmacological direct AMPK activation be a viable strategy to treat type 2 diabetes ?
We study mechanisms controlling of cell function, particularly in relation to diseases involving metabolic disorders, such as type 2 diabetes and cancer. Our main aim is to investigate whether drug targeting AMPK could be a strategy to treat diabetes. We also run the core mass spectrometry facility for protein analysis on the UCLouvain Brussels campus.
Metformin is the most prescribed medication used worldwide for the treatment of type 2 diabetes. Metformin action can partly be explained by activation of an enzyme, called AMPK. AMPK activation in tissues and cells switches on ATP producing pathways, such as glycolysis and fatty acid oxidation, while at the same time switching off ATP consuming processes, such as protein synthesis. In this way, AMPK counteracts ATP-depletion, such as occurs during anoxia or exercise in muscle.
We have made important contributions to the AMPK field by finding new targets in the control of glucose uptake, glycogen synthesis, glycolysis and protein synthesis. The search for AMPK targets is a main area of research, which we are pursuing using state-of-the-art mass spectrometry techniques. We use new direct AMPK activators including natural plant-derived compounds, particularly in muscle, liver and adipose tissue, to test their therapeutic potential for treating diabetes.
Mark Rider graduated in Biochemistry at Bristol University in 1979, then moved to University College London where he completed his PhD on the control of triglyceride synthesis in white adipose tissue under the supervision of David Saggerson. In 1983 he joined the group of Louis Hue at the de Duve Institute (then ICP) UCLouvain. He studied heart 6-phosphofructo-2-kinase (PFK-2) activation by insulin/PKB and AMPK during ischaemia. He was appointed "Chercheur Qualifié" FNRS in 1993 and Professor at UCLouvain in 2003. For well over 20 years, Mark Rider has taught biochemistry to undergraduate medical, dental and biomedical science students. He has continued to work on the control of cell function by AMPK and identified several novel targets. An important aspect of his work is the use of mass spectrometry for phosphorylation site identification and quantification of changes in protein expression.
Johanns M, Corbet C, Jacobs R, Drappier M, Bommer GT, Herinckx G, Vertommen D, Tajeddine N, Young D, Messens J, Feron O, Steinberg GR, Hue L, Rider MH.
Biochem J (2022) 479:1317-1336.
Johanns M, Kviklyte S, Chuang S-J, Corbeels K, Jacobs R, Schakman O, Duparc T, Cani PD, Bouzin C, Andersén H, Bohlooly-Y M, Van der Schueren B, Oscarsson J, Rider MH.
Mol Genet Metab (2019) 126:377-387.
Johanns M, Lai Y-C, Hsu M-F, Jacobs R, Vertommen D, Van Sande J, Dumont JE, Woods A, Carling D, Hue L, Viollet B, Foretz M, Rider MH.
Nat Commun (2016) 7, 10856.