The Laboratory of Cell Biology (LCB) studies the processing, transport, and metabolism of proteins and small molecules related to malignant transformation, metastasis, and multidrug resistance in cancer. The principal investigators of the laboratory, who are experts in molecular biology, genetics, biochemistry, structural biology, cellular regulation of cell growth and metabolism, resistance to anticancer drugs, and the physics of cell-matrix interactions, work on research projects related to those topics. The Multidrug Resistance Section studies the molecular basis of anticancer drug resistance, while the Transport Biochemistry Section investigates the biochemistry of energy-dependent transporters. Post-translational regulation of the tumor suppressor p53 and the roles of Wip1 in promoting cellular proliferation are the focus of the Chemical Immunology Section, while the DNA and Nucleoproteins Section is involved in computational and experimental studies of nucleic acid-protein interactions. The Biophysics Section develops novel EM-based approaches to determine single molecule and multisubunit structures and the Crystallography Section works on X-ray crystallography of membrane proteins and protein complexes. The Tissue Morphodynamics Unit studies how normal and cancer cells modify their environments to promote normal differentiation and cancer cell metastasis. Finally, our newest group, the RNA Metabolism and Epitranscriptomics Unit, investigates how the RNA epigenome modulates gene expression during development and when confronted by disease. (Please see webpages for LCB investigators for further details.) The LCB also includes two Cores, one in molecular modeling, and one in characterization of post-transcriptional protein processing. Joint journal clubs and data presentations among some sections, and laboratory-wide research seminars facilitate the sharing of expertise and help to foster collaborations among LCB staff.
Laboratory of Cell Biology Staff - 2017
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Mass Spectrometry Unit
The Mass Spectrometry Unit aims to advance CCR research by bringing cutting-edge protein-based technologies to the NCI CCR community to facilitate basic and translational research. Although mass spectrometry is a powerful technique, experimental design and sample preparation are critical for a successful outcome. By making available our expertise in mass spectrometry, we seek to help researchers with their proteomics experiments, beginning with initial experimental design and sample preparation and continuing through data interpretation and design of follow-up experiments. We collaborate on projects that explore protein-protein and protein-nucleic acid complexes, identify sites of protein post-translational modification or reaction with a small molecule, and quantify global changes in protein level upon protein knock-down/overexpression or cellular treatment. We also collaborate on projects using structural mass spectrometry approaches to study changes in protein conformation. For more information, see https://ccr.cancer.gov/Laboratory-of-Cell-Biology/lisa-m-jenkins
Electron Microscopy Core
Complex cellular processes such as signal transduction, gene expression, motility, and energy metabolism are often implemented using multi-component molecular assemblies. Understanding how these multi-component molecular machines function is an emerging frontier in cell biology, which will begin to define the information gap that exists between our knowledge of the structures of individual proteins and those of cellular organelles. As more networks of interacting proteins emerge from genomics and proteomics, the need for methods to illuminate these potentially disordered complexes will amplify. High resolution electron microscopy is uniquely poised to meet this challenge for a variety of biological specimens that are not amenable to investigation using either NMR or X-ray crystallographic techniques. A major focus of the Electron Microscopy Core is the structure determination of large multi-protein complexes by analyzing high resolution images of single molecules. In single particle electron microscopy, images containing large numbers of well-separated protein molecules are recorded using low-dose electron microscopy of frozen-hydrated samples. For more information, see https://ccr.cancer.gov/Laboratory-of-Cell-Biology/jacqueline-l-milne
CCR Molecular Modeling Core
The CCR Molecular Modeling Core, under the direction of Dr. Stewart Durell, was established to provide a convenient way for experimentalists to take advantage of molecular modeling and computational biology. In the framework of consultations, scientists can explore how such tools could benefit their projects. The Core then acts as a clearinghouse to help set-up and use appropriate software, and/or form collaborations with other scientists. Upon mutual agreement, Core personnel will enter into collaboration to do the modeling work themselves. All services of the Core are free of charge.
Symposium held in September:
Celebrating 30 Years of Research on Multidrug Resistance and ABC Transporters
September 22-23, 2016, NIH Campus, Building 35, Room 620-630
The discovery and characterization of P-glycoprotein as a mechanism of multidrug resistance is widely accepted as a seminal contribution to the ongoing effort to end death and alleviate suffering caused by cancer. In honor of the 30th anniversary of the cloning of the human MDR1 (ABCB1) gene, we held a day-and-a-half scientific symposium on the NIH campus in Bethesda, Maryland, on September 22 and 23, 2016. This event included current and former members of the MDR group in the Laboratory of Cell Biology, as well as collaborators and colleagues in the field. The first day of scientific talks and discussions was followed by a dinner in celebration of this anniversary.