Metabolic Signaling in the Sakamoto Group
The Sakamoto Group investigates fundamental molecular signaling mechanisms that control energy homeostasis and elucidates the regulation/function of potential therapeutic targets related to cardiometabolic disease.
The overarching aim of the Sakamoto Group is to elucidate molecular mechanisms underlying cellular energy sensing and restoration of metabolic balance. Our goal is to identify/validate drug candidates that ameliorate energetic imbalance in cardiometabolic disorders.
We study how post-translational modifications (e.g., reversible phosphorylation) and allosteric regulation of signaling proteins/metabolic enzymes control cellular energy balance and how dysfunctions of such molecular processes lead to cardiometabolic diseases. One of our key molecular targets is AMP-activated protein kinase (AMPK), a master regulator of energy metabolism. We aim to 1) uncover mechanisms by which AMPK controls insulin-independent nutrient transport and utilization in metabolic tissues such as skeletal muscle and liver, and 2) identify small-molecules/peptides that ameliorate metabolic dysfunctions/imbalance through modulating AMPK.
“The phosphorylation of AMPKβ1 is critical for increasing autophagy and maintaining mitochondrial homeostasis in response to fatty acid”
Published in Proc Natl Acad Sci in 2022. We have demonstrated a crucial role for a single phosphorylation site on the regulatory beta subunit of AMP-activated protein kinase (AMPK) to stimulate mitochondrial biogenesis and autophagy/mitophagy in response to increases in fatty acids.
“Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase"
Published in Nature Medicine in 2018. Metformin is a first-line drug for the treatment of individuals with type 2 diabetes. We have identified a key molecular mechanism by which metformin suppresses hepatic glucose production through 5´-AMP-dependent inhibition of fructose-1-6-bisphosphatase.
“The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver”
Published in Nature Communication in 2014. LKB1, originally identified as tumor suppressor, has recently been established as a master kinase that regulates metabolism and growth through AMPK and 12 other closely related kinases, including salt-inducible kinases (SIKs). We have demonstrated that the SIKs function as key gluconeogenic gate-keeper downstream of LKB1 through regulation of transcriptional co-activators and the gluconeogenic gene program in the liver.
|Addinsall, Alex Bernard||Postdoc||+4535333560|
|Ahwazi, Danial||Enrolled PhD Student||+4535325398|
|Fraguas Bringas, Conchita||PhD Fellow||+4535321343|
|Hellberg, Anna Kristina||Staff Scientist||+4520894788|
|Holgersen Bryde, Tenna||PhD Fellow||+4581616072|
|Jensen, Marianne Agerholm||Staff Scientist||+4535325063|
|Konopka, Veronika Lauren||Master Student|
|Liu, Hongling||External, Ph.d Student|
|Luda, Katarzyna Maria||Postdoc|
|Morton, Nicholas Michael||Visiting Professor|
|Negoita, Ionela Florentina||Postdoc|
|Pradas Juni, Marta||Staff Scientist||+4535324485|