Graeber, Thomas - University of California, Los Angeles

个人简介

Professor, Molecular & Medical Pharmacology Member, Bioinformatics GPB Home Area, CTSI, California NanoSystems Institute, Cell & Developmental Biology GPB Home Area, Crump Institute for Molecular Imaging, Genetics & Genomics GPB Home Area, Molecular Pharmacology GPB Home Area, Molecular, Cellular & Integrative Physiology GPB Home Area, Physics & Biology in Medicine GPB Home Area Research Fellow, Alfred P. Sloan Foundation

研究领域

Our group is working to understand cancer signaling and metabolism from a systems view. We focus on developing genome-, proteome- and metabolome-wide assays, and applying these assays to measuring and computationally modeling aberrant function in cancer cells. Through collaboration with clinical scientists, we work directly with patient samples and aim to translate our discoveries to clinical applications. We collect high dimensionality data using mass spectrometry-based phosphoproteomic and metabolomic profiling. To integratively analyze this data, we develop computational approaches aimed at overlaying the raw data with known signaling and metabolic network structures. A point of emphasis is how cellular signaling and metabolism is rewired when cancers become resistant to molecularly targeted therapies (e.g. the mutant BRAF kinase inhibitor used in melanoma). Our results have pointed us to the contributions of feedback loops in maintaining cancer signaling and metabolism homeostasis, and we are exploring therapeutic approaches to perturbing these loops synergistically to disrupt cellular equilibrium and induce death in cancer cells. In modeling cancer, one of our goals is to identify minimal sets of informative components that best reflect the state of the cell and serve as molecular targets for diagnostics, imaging, and patient tailored treatment. As with all of systems biology, our research relies on an interdisciplinary approach that merges biology, chemistry, mathematics and computation / bioinformatics .

近期论文

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Graham, NA, A Minasyan, A Lomova, A Cass, NG Balanis, M Friedman, S Chan, S Zhao, A Delgado, J Go, L Beck, C Hurtz, C Ng, R Qiao, J ten Hoeve, N Palaskas, H Wu, M Müschen, AS Multani, E Port, S Larson, N Schultz, D Braas, H Christofk, I Mellinghoff, & TG Graeber Recurrent patterns of DNA copy number alterations in tumors reflect metabolic selection pressures. Molecular Systems Biology. 2017; 13(2): 914. Chan Lai N, Chen Zhengshan, Braas Daniel, Lee Jae-Woong, Xiao Gang, Geng Huimin, Cosgun Kadriye Nehir, Hurtz Christian, Shojaee Seyedmehdi, Cazzaniga Valeria, Schjerven Hilde, Ernst Thomas, Hochhaus Andreas, Kornblau Steven M, Konopleva Marina, Pufall Miles A, Cazzaniga Giovanni, Liu Grace J, Milne Thomas A, Koeffler H Phillip, Ross Theodora S, Sanchez-Garcia Isidro, Borkhardt Arndt, Yamamoto Keith R, Dickins Ross A, Graeber Thomas G, Muschen Markus Metabolic gatekeeper function of B-lymphoid transcription factors. Nature. 2017; 1-5. Shin Daniel Sanghoon, Zaretsky Jesse M, Escuin-Ordinas Helena, Garcia-Diaz Angel, Hu-Lieskovan Siwen, Kalbasi Anusha, Grasso Catherine S, Hugo Willy, Sandoval Salemiz, Torrejon Davis Y, Palaskas Nicolaos, Rodriguez Gabriel Abril, Parisi Giulia, Azhdam Ariel, Chmielowski Bartosz, Cherry Grace, Seja Elizabeth, Berent-Maoz Beata, Shintaku I Peter, Le Dung T, Pardoll Drew M, Diaz Luis A, Tumeh Paul C, Graeber Thomas G, Lo Roger S, Comin-Anduix BegoÃ±a, Ribas Antoni Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. Cancer discovery. 2017; 7(2): 188-201. Momcilovic Milica, Bailey Sean T, Lee Jason T, Fishbein Michael C, Magyar Clara, Braas Daniel, Graeber Thomas, Jackson Nicholas J, Czernin Johannes, Emberley Ethan, Gross Matthew, Janes Julie, Mackinnon Andy, Pan Alison, Rodriguez Mirna, Works Melissa, Zhang Winter, Parlati Francesco, Demo Susan, Garon Edward, Krysan Kostyantyn, Walser Tonya C, Dubinett Steven M, Sadeghi Saman, Christofk Heather R, Shackelford David B Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer. Cell reports. 2017; 18(3): 601-610. Titz Bjoern, Lomova Anastasia, Le Allison, Hugo Willy, Kong Xiangju, Ten Hoeve Johanna, Friedman Michael, Shi Hubing, Moriceau Gatien, Song Chunying, Hong Aayoung, Atefi Mohammad, Li Richard, Komisopoulou Evangelia, Ribas Antoni, Lo Roger S, Graeber Thomas G JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma. Cell discovery. 2016; 2(3): 16028.