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Cancer drug’s secret to resistance
Dr. Matt Petroski and colleagues outline a new method to test a tumor’s resistance to an experimental therapy before testing the drug in patients—providing a new path toward personalized medicine.
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Cellular sensor’s 3D structure reveals new cancer clues
Dr. Francesca Marassi and colleagues determined the 3D structure of a complete, unmodified G-protein-coupled receptor in its native environment: embedded in a lipid membrane.
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Molecular switch that allows melanoma to resist therapy
Dr. Ze’ev Ronai and his team identify protein kinase Cɛ as a molecular switch that determines tumor-promoting or -suppressing activity in skin cells.
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Studying signal transductionSignal transduction research concerns the mechanisms cells use to interpret, integrate, and act upon information received by cell surface receptors or by intracellular signals elicited in response to stress or damage. The conversion of this information into biochemical events that trigger specific pathways, control gene activity, and modify cell behavior are among the main topics studied in this program.
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What is signal transduction? Program director Ze'ev Ronai, Ph.D. explains.
The Signal Transduction Program focuses on research questions related to the control of cell cycle progression, cell proliferation, DNA damage checkpoint function, stress response pathways, and cellular senescence. The emphasis lies on studies of protein phosphorylation/dephosphorylation, ubiquitin and ubiquitin-like proteins, chromatin organization, and transcription factors that play important roles in these processes. The projects employ state-of-the art technologies, including comprehensive proteomic and phosphoproteomic profiling, as well as high-content and high-throughput screening of siRNA and chemical compound libraries.
How our research helps improve health
Many pathologic disorders in humans arise from malfunctioning signal transduction processes in particular cells or tissues. A substantial proportion of modern-day drug discovery efforts is founded on the premise that pharmacologic manipulation of signaling proteins will prove beneficial in the prevention and treatment of major human afflictions, including cancer and neurodegenerative diseases. Discoveries by scientists in this program have resulted in several new therapies currently in clinical testing, including drugs that block signal transduction proteins needed for cancer cell division and survival and cancer gene therapies that reprogram the genome of tumor cells, making them easier to kill with chemotherapy or radiation.
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Read more about other developments from the Signal Transduction program. |
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Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK.
Mace PD, Wallez Y, Egger MF, Dobaczewska MK, Robinson H, Pasquale EB, Riedl SJ.
Nat Commun. 2013 Apr 9;4:1681. doi: 10.1038/ncomms2687.
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CAND1 controls in vivo dynamics of the cullin 1-RING ubiquitin ligase repertoire.
Wu S, Zhu W, Nhan T, Toth JI, Petroski MD, Wolf DA.
Nat Commun. 2013 Mar 27;4:1642. doi: 10.1038/ncomms2636.
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The e3 ubiquitin ligase siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity.
Qi J, Tripathi M, Mishra R, Sahgal N, Fazil L, Ettinger S, Placzek WJ, Claps G, Chung LW, Bowtell D, Gleave M, Bhowmick N, Ronai ZA.
Cancer Cell. 2013 Mar 18;23(3):332-46. doi: 10.1016/j.ccr.2013.02.016.
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Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis.
McDonough PM, Maciejewski-Lenoir D, Hartig SM, Hanna RA, Whittaker R, Heisel A, Nicoll JB, Buehrer BM, Christensen K, Mancini MG, Mancini MA, Edwards DP, Price JH.
PLoS One. 2013;8(2):e55511. doi: 10.1371/journal.pone.0055511. Epub 2013 Feb 6.
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HTS by NMR of combinatorial libraries: a fragment-based approach to ligand discovery.
Wu B, Zhang Z, Noberini R, Barile E, Giulianotti M, Pinilla C, Houghten RA, Pasquale EB, Pellecchia M.
Chem Biol. 2013 Jan 24;20(1):19-33. doi: 10.1016/j.chembiol.2012.10.015.
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Single-particle EM reveals extensive conformational variability of the Ltn1 E3 ligase.
Lyumkis D, Doamekpor SK, Bengtson MH, Lee JW, Toro TB, Petroski MD, Lima CD, Potter CS, Carragher B, Joazeiro CA.
Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1702-7. doi: 10.1073/pnas.1210041110. Epub 2013 Jan 14.
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Research - Cancer - Signal Transduction: Recent Publications |
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