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John Blenis, PhD

Professor, Department of Cell Biology, Harvard Medical School

Contact Info

John Blenis
Harvard Medical School
240 Longwood Avenue
Boston, MA, 02115
Mailstop: Bldg LHRRB/Rm 605
Phone: 617-432-4848
Fax: 617-432-1144
jblenis@hms.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Mitogenic/Oncogenic Signaling via Ras and the ERK-MAP kinase/RSK pathway.

The Mitogen-Activated Protein Kinases (or ERKs) and the ERK-regulated kinases (or RSKs) have been established as major participants in the regulation of cell proliferation and differentiation, but when improperly activated contribute to malignant transformation. Critical details regarding the regulation of this signaling system remain unclear. For example; what signals are responsible for the transient versus prolonged ERK/RSK activation and how does this translate into a cell context-dependent proliferation or differentiation response, what regulates the cytoplasmic and nuclear localization of these signaling enzymes, and how do these kinases regulate immediate-early gene expression? In addition, novel mitogen-regulated kinases activated downstream of the G-protein Ras are being characterized and their role in growth control investigated.


Mitogenic/Oncogenic Signaling via PI3-kinase and the p70-S6 Protein Kinase Pathway.

Together with the ERK/RSK pathway, the p70-S6 kinase signaling system is known to contribute to G1 cell cycle transition. The role of p70-S6 kinase in the regulation of protein translation and gene expression is being actively examined. A variety of signal transducing proteins have been shown to participate in p70-S6 kinase regulation. These include lipid-modifying enzymes such as phosphatidylinositol 3-kinase and PLCg, PI3-kinase-modulated kinases such as Akt/PKB, the phosphatidylinositol-like protein kinase FRAP/mTOR/RAFT, small G-proteins Cdc42 and Rac1, the proto-oncogenic exchange factors for these G proteins Dbl and TIAM-1 and the tumor suppressors, PTEN, TSC1/2, and LKB. How information from these various growth factor-regulated signal transducers and nutrient-sensing pathways converge to activate p70-S6 kinase is still unclear and is being investigated. Additional protein kinases are now being identified that participate in these signaling systems and their characterization is ongoing.


Protein Kinase Signaling Promoting Survival in Chemo-Resistant Tumor Cells.

We have completed an RNAi-based screen to identify kinases involved in promoting survival in cancer cells resistant to classical chemotherapeutics. All candidate targets are now being validated, characterized and evaluated as potential future targets for drug development.

Publications

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