Research summary
Research from this group spans the genetic underpinnings of brain tumors and the metabolic kinase networks that regulate glucose homeostasis and energy stress responses. A 2007 review in Genes & Development synthesized the genetics, biology, and therapeutic landscape of malignant astrocytic gliomas, the most common and lethal intracranial tumors [1]. The article described how glioblastoma progresses through diffuse infiltration of brain tissue, resists standard and targeted regimens, and ultimately destroys surrounding neural structures. It argued that converging advances in stem cell biology, cell signaling, computational genomics, and engineered model systems have reshaped understanding of glioma initiation and behavior, opening avenues for mechanism-based therapy. Shifting to metabolic regulation, a 2005 Science paper investigated the role of the Peutz-Jeghers tumor suppressor LKB1 in hepatic glucose control [2]. Conditional deletion of LKB1 in adult mouse liver almost entirely abolished AMP-activated protein kinase (AMPK) activity, producing hyperglycemia accompanied by elevated transcription of gluconeogenic and lipogenic genes. Mechanistically, loss of LKB1 caused dephosphorylation and nuclear translocation of the CREB coactivator TORC2, which drove expression of PGC-1alpha and downstream gluconeogenic output. The work also linked LKB1 to the therapeutic action of metformin, indicating that the drug requires intact LKB1-AMPK signaling to suppress hepatic glucose production. A companion 2004 PNAS study established the upstream biochemistry of this pathway by identifying LKB1 as the long-sought AMPK kinase in mammalian cells [3]. Combining biochemical reconstitution with genetic loss-of-function, the authors showed that LKB1 directly phosphorylates Thr-172 on the AMPK alpha subunit in vitro, activating its catalytic activity. They further demonstrated that LKB1 is the dominant regulator of AMPK activation across multiple mammalian cell types and that this axis controls apoptotic responses to cellular energy stress. Together, these papers position LKB1 as a hub linking tumor suppression, energy sensing, and pharmacological glucose control, while parallel work outlines a framework for translating molecular insight into glioma treatment. The body of work illustrates a coherent interest in how kinase signaling networks integrate nutrient status, proliferation, and disease progression across cancer and metabolic contexts.
Recent publications
- Malignant astrocytic glioma: genetics, biology, and paths to treatmentDOI
- Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNADOI
- Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the MicroenvironmentDOI
- Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose MetabolismDOI
- Hepatocellular carcinoma pathogenesis: from genes to environmentDOI
- Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathwayDOI
- The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of MetforminDOI
- ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGFDOI
- The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stressDOI
- HDAC2 negatively regulates memory formation and synaptic plasticityDOI
The lab page does not clearly state student acceptance status. Email the professor directly to confirm.
How to apply
Email Ronald A. DePinho 6-12 months before your application deadline. Read several recent papers and reference specific work in your message. Use our how to email a Japanese professor guide for the proven email structure.
For applications via MEXT scholarship: see our MEXT 2027 complete guide and university-specific University Recommendation track.
External profiles
- ORCID: https://orcid.org/0000-0002-5625-577X
- OpenAlex: openalex.org
Profile compiled from public sources (Researchmap, OpenAlex, Keio University faculty directory). Last refreshed 2026-05. Report incorrect information.