Ben Major

Professor of Cell Biology and Physiology, Professor of Otolaryngology, Alan A. and Edith L. Wolff Professorship in Cell Biology and Physiology

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    The Major lab studies how perturbation of specific signal transduction pathways contributes to the initiation, progression and dissemination of cancer. We employ a "systems level" integrative discovery platform to characterize pathway dynamics in normal and cancer cell models. Specifically, we use protein mass spectrometry to define the protein-protein interaction/proximity networks and phosphorylation modification for the WNT and NRF2/oxidative stress signaling pathways. We then annotate the nodes within the network for function, as determined by established and novel functional genomic screening technologies. Integration of these data with cancer-associated mutation data gene expression yields a powerful tool for oncological discovery - a cancer annotated physical/functional map. Critical to our success is the development and implementation of computational scoring algorithms, relational database construction and data visualization. Ultimately, the models and hypotheses produced are challenged through mechanistic studies employing cultured cancer cells, mouse models, clinical tissue and various biochemical and cell biological systems. The diverse approach we take to study signal transduction provides a rich learning environment for students. In addition to standard biochemical, cell biological and molecular biology approaches, scientists in my lab are running loss- and gain-of-function genetic screens, performing drug screens, developing transcriptional classifiers of clinical importance, and running an array of quantitative mass spectrometry experiments. They are also learning and developing new computational approaches for data integration, analysis and hypothesis generation. Since 2009, I have mentored 10 PhD graduate students and 2 computer science MS students (5 completed their PhDs; 2 completed MS degree) and 12 postdoctoral scientists. I served as the Associate Director of the UNC Cancer Cell Biology Training Program T32 (pre-doc), and am currently mentor for two HHMI Gilliam Fellows. Mentorship excellence and student success are defining priorities for the lab, evidenced in part by leadership in mentor training and a recent mentorship award for excellence in basic science. We are recruiting enthusiastic scientists into the following general research fields: -- KEAP1/NRF2 oxidative stress response pathway in lung cancer, head and neck cancer and esophageal cancer. Basic mechanisms, biochemistry, proteomics, drug screens, mouse models, clinical trials. -- WNT signaling pathway in pancreas cancer and lung cancer. Basic mechanisms, biochemistry, proteomics, time resolved protein-protein interactions. -- Understudied kinases altered in human disease. Protein-protein interaction and proximity networks. Crispr-A and Crispr-I genetic screens. ORF screens. Phosphoproteomics. -- Proteomics. Phospho- and ubiquitylation proteomics. Kinase enrichment mass spectrometry. Multiplex quantitative mass spectrometry. Proteoinformatics. Data acquisition algorithm development. Complete List of Published Work:


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