Brian A. Hemmings
Targeting the cancer kinome
Judging simply by the abundance of protein kinase and protein phosphatase genes, protein phosphorylation is a very important regulatory mechanism. Our current work focuses on the role of these enzymes in eukaryotic signaling pathways and their possible implications in human diseases.
Signal transduction pathways in mammalian cells function through the coordinated activation, or inactivation of protein kinases and phosphatases localized in the cell membrane, cytoplasm or nucleus. Many human diseases result from deregulation of signal transduction pathways; for example, the proliferation signal pathways of cancer cells are permanently upregulated following mutation of key regulatory enzymes.
Our current research activities focus on targeting novel kinases involved in the development and progression of glioblastoma, ovarian cancer and lymphoma with the ultimate aim of finding new personalized therapeutic strategies.
Most highly cited paper
Cross DAE, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Tang F, Zhang L, Xue G, Hynx D, Wang Y, Cron PD, Hundsrucker C, Hergovich A, Frank S, Hemmings BA, Schmitz-Röhmer D (2014) hMOB3 modulates MST1 apoptotic signaling and supports tumor growth in glioblastoma multiformeCancer Res 74:3779-89
Grzmil M, Huber RM, Hess D, Frank S, Hynx D, Moncayo G, Klein D, Merlo A, Hemmings BA (2014) MNK1 pathway activity maintains protein synthesis in rapalog-treated gliomasJ Clin Invest 124:742-754
Wang Y, Moncayo G, Morin P Jr, Xue G, Grzmil M, Lino MM, Clément-Schatlo V, Frank S, Merlo A, Hemmings BA (2013) Mer receptor tyrosine kinase promotes invasion and survival in glioblastoma multiformeOncogene 32:872-882
Xue G, Restuccia DF, Lan Q, Hynx D, Dirnhofer S, Hess D, Rüegg C, Hemmings BA (2012) Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axesCancer Discov 2:248-259
Zhuravleva E, Gut H, Hynx D, Marcellin D, Bleck CK, Genoud C, Cron P, Keusch JJ, Dummler B, Esposti MD, Hemmings BA (2012) Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver developmentMol Cell Biol 32:2685-2697
Cornils H, Kohler RS, Hergovich A, Hemmings BA (2011) Downstream of human NDR kinases: Impacting on c-myc and p21 protein stability to control cell cycle progressionCell Cycle 10:1897-904
Lu S, Nie J, Luan Q, Feng Q, Xiao Q, Chang Z, Shan C, Hess D, Hemmings BA, Yang Z (2011) Phosphorylation of the twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodelingPLoS One 6:e19251.
Grzmil M, Morin P Jr, Lino MM, Merlo A, Frank S, Wang Y, Moncayo G, Hemmings BA (2011) MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-ß signaling pathway in human glioblastomaCancer Res 71:2392-402
Cornils H, Kohler RS, Hergovich A, Hemmings BA (2011) Human NDR kinases control G(1)/S cell cycle transition by directly regulating p21 stabilityMol Cell Biol 31:1382-95
Fayard E, Xue G, Parcellier A, Bozulic L, Hemmings BA (2011) Protein kinase B (PKB/Akt), a key mediator of the PI3K signaling pathwayCurr Top Microbiol Immunol (CTMI) (ed) Vogt P, Rommel, Vanhaesebroeck B., Springer, Heidelberg 346:31-56
Restuccia DF, Hemmings BA (2010) From man to mouse and back again: advances in defining tumor AKTivities in vivoDis Model Mech 3:705-20
Kohler RS, Schmitz D, Cornils H, Hemmings BA, Hergovich A (2011) Differential NDR/LATS interactions with the human MOB family reveal a negative role for human MOB2 in the regulation of human NDR kinasesMol Cell Biol 30:4507-20
Cornils H, Stegert MR, Hergovich A, Hynx D, Schmitz D, Dirnhofer S, Hemmings BA (2010) Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphomaSci Signal 3:ra47
Hergovich A, Hemmings BA (2010) TAZ-mediated crosstalk between Wnt and Hippo signalingDev Cell 18(4):508-509
Vichalkovski A, Gresko E, Hess D, Restuccia DF, Hemmings BA (2010) PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damageOncogene 29:3554-65
Bozulic L, Hemmings BA (2009) PIKKing on PKB: regulation of PKB activity by phosphorylationCurr Opin Cell Biol 21:256-261
Grzmil M, Hemmings BA (2009) Deregulated signalling networks in human brain tumoursBiochim Biophys Acta 1804(3):476-483
Hergovich A, Hemmings BA (2009) Mammalian NDR/LATS protein kinases in hippo tumor suppressor signalingBiofactors 35(4):338-45
Hergovich A, Kohler RS, Schmitz D, Vichalkovski A, Cornils H, Hemmings BA (2009) The MST1 and hMOB1 tumor suppressors control human centrosome duplication by regulating NDR kinase phosphorylationCurr Biol 19:1692-702
Parcellier A, Tintignac LA, Zhuravleva E, Cron P, Schenk S, Bozulic L, Hemmings BA (2009) Carboxy-Terminal Modulator Protein (CTMP) is a mitochondrial protein that sensitizes cells to apoptosisCell Signal 21:639-650
Parcellier A, Tintignac LA, Zhuravleva E, Dummler B, Brazil DP, Hynx D, Cron P, Schenk S, Olivieri V, Hemmings BA (2009) The Carboxy-Terminal Modulator Protein (CTMP) regulates mitochondrial dynamicsPLoS ONE. 4:e5471. Epub 2009 May 7
Park J, Feng J, Li Y, Hammarsten O, Brazil DP, Hemmings BA (2009) DNA-dependent protein kinase-mediated phosphorylation of protein kinase B requires a specific recognition sequence in the C-terminal hydrophobic motifJ Biol Chem 284:6169-6174
Restuccia D, Hemmings BA (2009) Blocking Akt-ivityScience 325:1083-1084