Joseph Avruch M.D.
Signal transduction pathways controlling growth and metabolism
The Avruch laboratory studies mammalian signal transduction pathways. Over time, the laboratory has described the composition, architecture and regulation of signal transduction pathways operating downstream of the insulin receptor and other receptor tyrosine kinases (S6 kinases, Raf, Ras, Rheb), inflammatory cytokines (Map3ks, Map2ks and Mapks of the SAPKs/Jnk pathway), nutrients (mTOR complex1, Rag GTPases), cell-cell contact (Mst1/Mst2 operating in the mammalian Hippo pathway) and cdk1/Plk1 in control of mitotic progression (the Nek9-Nek6/7 kinase cascade). At present, three projects are ongoing:
1. Noriko Oshiro, Joseph Rapley, Joseph Avruch Amino Acids Activate Mammalian Target of Rapamycin (mTOR) Complex 1 without Changing Rag GTPase Guanyl Nucleotide Charging. J Biol Chem. 2014; 289(5): 2658–2674. PMCID: PMC3908400
2. Ning Dai, Joseph Rapley, Matthew Angel, M. Fatih Yanik, Michael D. Blower, Joseph Avruch mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry. Genes Dev. 2011; 25(11): 1159–1172. PMCID: PMC3110954.
3. Ning Dai, Jan Christiansen, Finn C. Nielsen, Joseph Avruch. mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts
Genes Dev. 2013; 27(3): 301–312. PMCID: PMC3576515
4. Dawang Zhou, Benjamin D. Medoff, Lanfen Chen, Lequn Li, Xian-feng Zhang, Maria Praskova, Matthew Liu, Aimee Landry, Richard S. Blumberg, Vassiliki A. Boussiotis, Ramnik Xavier, Joseph Avruch The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc Natl Acad Sci U S A. 2008; 105(51): 20321–20326. PMCID: PMC2600581.
5. Dawang Zhou, Claudius Conrad, Fan Xia, Ji-Sun Park, Bernhard Payer, Yi Yin, Gregory Y. Lauwers, Wolfgang Thasler, Jeannie T. Lee, Joseph Avruch, Nabeel Bardeesy. Mst1 and Mst2 maintain hepatocyte quiescence and suppress the development of hepatocellular carcinoma through inactivation of the Yap1 oncogene. Cancer Cell. 2009; 16(5): 425–438. PMCID: PMC3023165
6. Fan Mou, Maria Praskova, Fan Xia, Denille Van Buren, Hanno Hock, Joseph Avruch, Dawang Zhou. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med. 2012; 209(4): 741–759. PMCID: PMC3328371.