BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Diane S. Lidke Associate Professor eRA COMMONS USER NAME (credential, e.g., agency login) DSLIDKE EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Nebraska Wesleyan University, Lincoln, Nebraska University of Minnesota, Minneapolis, Minnesota Max Planck Institute for Biophysical Chemistry Goettingen, Germany B.S. 1994 Ph.D. 2002 Postdoc 2002-2005 Physics Biophysical Sciences & Medical Physics Fluorescence Microscopy/ Cell Signal Transduction A. Personal Statement The overall theme of my research is the application of fluorescence microscopy and biophysical techniques to the study of cell signal transduction. This involves the study of the spatial-temporal organization of membrane proteins and how these are altered in diseased cells or influenced by therapeutics. In particular, we study the erbB family of receptor tyrosine kinases that is implicated in many kinds of cancer. My expertise in live cell imaging includes techniques such as FRAP, FCS, FRET, hyperspectral imaging and single particle tracking as well as development of techniques for live cell labeling of proteins of interest with fluorescent protein and/or quantum dot probes. I also work with members of the UNM Spatiotemporal Modeling Center to integrate quantitative measurements of biological processes into modeling platforms of signal transduction. B. Positions and Honors Professional Appointments 2005-2006 Research Asst. Prof., Department of Pathology, University of New Mexico School of Medicine 2006-2012 Assistant Professor, Department of Pathology, University of New Mexico School of Medicine 2012-present Associate Professor, Department of Pathology, University of New Mexico School of Medicine Honors and Awards 2002-2005 Max-Planck-Gesellschaft Fortbildungsstipendium, Post-doctoral Fellowship 2006 Selected participant in the UK-Germany Frontiers of Science Symposium 2008-2011 Human Frontiers Science Program Young Investigator Award 2009-2014 NSF Faculty Early Career Development (CAREER) Award 2010 UNM-HSC Jr. Faculty Excellence in Research Award 2011 Biophysical Society’s Margaret Oakley Dayhoff Award Reviewer for National and International Funding Agencies. 2010 NSF Cellular Organization review panel; 2011-2012 NSF Membrane Trafficking and Biogenesis review panel; Ad hoc reviews for NSF (2009 – present) Ad-hoc Reviewer for Peer Reviewed Journals. ACS Nano, Molecular Biology of the Cell, Biophysical Journal, Nano Letters, Journal of Microscopy, PNAS, Journal of Biological Chemistry, Journal of Cell Science, Blood, PLOS One Memberships. Biophysical Society 1998-present; ACSB (2010-present); AAAS (2010-present). C. Selected Peer-reviewed Publications Most relevant to the current application 1. D.S. Lidke, P. Nagy, R. Heintzmann, D.J. Arndt-Jovin, J.N. Post, H. Grecco, E.A. Jares-Erijman, and T.M. Jovin. “Quantum Dot ligands provide new insights into receptor-mediated signal transduction.” Nature Biotechnology, 22: 198 (2004) 2. D.S. Lidke, K.A. Lidke, B. Reiger, T.M. Jovin and D.J. Arndt-Jovin. “Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors.” Journal of Cell Biology, 170: 619 (2005) PMC2171515 3. N.L. Andrews, K.A. Lidke, J.R. Pfeiffer, A.R. Burns, B.S. Wilson, J.M. Oliver and D.S. Lidke. “Actin restricts FcεRI diffusion and facilitates antigen induced immobilization.” Nature Cell Biology, 10:955-963 (2008) PMC3022440 4. N.L. Andrews, J.R. Pfeiffer, A.M. Martinez, D.M. Haaland, R.W. Davis, T. Kawakami, J.M. Oliver, B.S. Wilson and D.S. Lidke. “Small, mobile FcεRI aggregates are signaling competent.” Immunity, 31: 469479 (2009) PMC2828771 5. S.T. Low-Nam, K.A. Lidke, P.J. Cutler, R.C. Roovers, P.M.P. van Bergen en Henegouwen, B.S. Wilson, D.S. Lidke. “ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand.” Nature Structural & Molecular Biology, 18: 1244-1249 (2011) PMC3210321 Additional recent publications of importance to the field (in chronological order) 1. H.E. Grecco, K.A. Lidke, R. Heintzmann, D.S. Lidke, C. Spagnuolo, O.E. Martinez, E.A. Jares-Erijman and and T.M. Jovin. “Ensemble and single particle photophysical properties (two-photon excitation, anisotropy, FRET, lifetime, spectral conversion) of commercial quantum dots in solution and in live cells.” Microscopy Research and Technique, 65: 169-179 (2004) 2. A. Cambi, D.S. Lidke, D.J. Arndt-Jovin, C.G. Figdor and T.M. Jovin. “Ligand-conjugated quantum dots monitor antigen uptake and processing by dendritic cells.” Nano Letters, 7:970 (2007) 3. S. Yang, M. Raymond-Stintz, W. Ying, J. Zhang, D.S. Lidke, S.L. Steinberg, J.M. Oliver and B.S. Wilson. “Mapping erbB receptors on breast cancer cell membranes during signal transduction.” Journal of Cell Science, 120:2763-2773 (2007) 4. M. Xue, G. Hsieh, M. Raymond-Stintz, J. Pfeiffer, D. Roberts, S.L. Steinberg, J.M. Oliver, E.R. Prossnitz, D.S. Lidke, and B.S. Wilson. “Activated FPR and FcRI Occupy Common Domains for Signaling and Internalization.” Molecular Biology of the Cell, 18:1410-1420 (2007) PMC1838997 5. J.L. Smith, D.S. Lidke, M. Ozbun. “Virus activated filopodia promote human papillomavirus type 31 uptake from the extracellular matrix.” Virology, 381:16-21 (2008) (cover) PMC2862147 6. D.M. Haaland, H.D.T. Jones, M.H. Van Benthem, M.B. Sinclair, D.K. Melgaard, C.L. Stork, M.C. Pedroso, P. Liu, A.R. Brasier, N.L. Andrews, and D.S. Lidke. “Hyperspectral confocal fluorescence imaging: Exploring alternative multivariate curve resolution approaches.” Applied Spectroscopy. 63: 271-279 (2009) 7. D.S. Lidke and B.S. Wilson. “Caught in the act: quantifying protein behavior in living cells.” An invited (and peer-reviewed) review for Trends in Cell Biology, 19: 566-574 (2009) (cover) PMC2783887 8. D.S. Lidke, F. Huang, J.N. Post, B. Rieger, J. Wilsbacher, J.L. Thomas, J. Pouysségur, T.M. Jovin and P. Lenormand. “ERK nuclear translocation is dimerization-independent but controlled by the rate of phosphorylation.” Journal of Biological Chemistry. 285:3092-3102 (2010) PMC2823437 *Selected “Paper of the Week” 9. A. Carroll-Portillo, K. Spendier, J. Pfeiffer, G. Griffiths, H. Li, K.A. Lidke, J.M. Oliver, D.S. Lidke, J.L. Thomas, B.S. Wilson, J.A. Timlin. “Formation of a mast cell synapse: FcεRI membrane dynamics upon binding mobile or immobilized ligands on surfaces.” Journal of Immunology, 184: 1328-1338 (2010) PMC2944771 10. S. de Keijzer, M. Meddens, D. Kilic, B. Joosten, I. Reinieren-Beeren, D.S. Lidke, S. Grinstein and A. Cambi. “Interleukin-4 alters early phagosome phenotype by modulating class I PI3K dependent lipid remodeling and protein recruitment.” PLoS ONE. 6(7): e22328. doi:10.1371/journal.pone.0022328 (2011) PHS 398/2590 (Rev. 06/09) Page 2 Continuation Format Page D. Research Support Ongoing Research Support 1R01GM100114 (Lidke) 5/1/12 – 2/28/17 2.40 CM NIH/NIGMS $1,439,070 Single Molecule Imaging to Quantify FcRI Signaling Dynamics The major goals of this project are to quantify the protein interactions and dynamics at the molecular level using innovative imaging techniques to further the fundamental understanding of mast cell signaling. Role: PI RGY Program Grant (Garcia-Parajo, Lidke) 9/1/12 - 8/31/15 0.60 CM Human Frontiers Science Program $100,000 Nano-Mechano-Biology: spatiotemporal remodeling of membrane nanoplatforms under mechanical forces The major goal of this project is to elucidate the influence of mechanical stress on membrane architecture, cell signaling and physiological response in Dendritic Cells. Role: Co-PI MCB-0845062 CAREER Award (Lidke) 1/1/09-12/31/14 3.00 CM NSF $95,541 Elucidating the regulation mechanisms of erbB signaling using quantitative imaging The major goals of this project are to compare the behavior of wild type and mutant erbB1 using fluorescence microscopy techniques. Role: PI P50GM085273 (Oliver) 8/1/09-7/31/14 2.40 CM NIH/NIGMS $2,262,170 New Mexico Center for the Spatiotemporal Modeling of Cell Signaling Study of cell signaling using computational modeling and experimental techniques. Role: Co-director of the Super-resolution Imaging Core and Quantitative Measurement Core. K25CA131558/09-059-UNM (Halasz) 1/1/08-12/31/13 0.60 CM Sub-award from NIH Grant to Halasz $13,622 Spatial Monte Carlo models for VEGF binding on the cell membrane This grant is to measure and model the spatiotemporal regulation of VEGF signaling. The UNM subaward is for SPT experiments to gather information about VEGFR spatial dynamics. Role: Co-investigator 5R01AI051575-07 (Wilson) 2/15/09 - 1/31/14 0.60 CM NIH/NIAID $279,825 Mapping for Special Domains for FcεRI Signaling & Internalization This project focuses on composition of membrane microdomains associated with immunoreceptor signaling Role: Co-investigator 5R01CA119232-05 (Wilson) 7/1/09 – 6/30/13 0.60 CM NIH/NCI $211,321 MSM Mapping & Modeling ErbB Receptor Membrane Topograpy This project is aligned with the IMAG/MSM program; it involves quantitative measurements and mathematical modeling of membrane signaling proteins, then extends to tumor modeling based upon data from xenografts. Role: Co-investigator 1R01CA132136-01 (Ozbun) 12/1/08–11/30/12 0.60 CM NIH Entry of oncogenic HPVs into human keratinocytes This goal of this project is to elucidate the mechanisms of HPV host entry. Role: Co-investigator for imaging. PHS 398/2590 (Rev. 06/09) Page 3 Continuation Format Page Research Support Completed During the Last Three Years RGY0074/2008 Young Investigator Award (Lidke) 9/1/08 - 8/31/11 Human Frontiers Science Program Integrating Single Molecule Imaging Techniques to Unravel Mast-Dendritic Cell Interplay This project is to characterize the potential mast cell – dendritic cell synapse. Role: PI RR024438 (K. Lidke) 2/1/09–12/31/11 NIH/NCRR A hyperspectral microscope optimized for spectrally multiplexed live cell imaging A fast, line-scanning spectral microscope for multi-color quantum dot single particle tracking. Role: Co-investigator Oxnard Foundation Award (Lidke) 2/1/07-1/31/09 Understanding ErbB Signaling in Cancer This internal grant provided pilot funding for the development of fluorescent probes and single molecule techniques to characterize erbB receptor dynamics. Role: PI Sub-award from American Cancer Society IRG-92-024 (J. Oliver) 4/1/08-3/31/09 Real-time imaging of erbB behavior in primary cancer cells This internal grant provided pilot funding for development of imaging primary tumor tissue. Role: PI Sandia-University Research Program (Lidke) 10/1/06 -9/31/08 Hyperspectral Imaging and Multi-color Single Particle Quantum Dot Tracking This funding from Sandia National Laboratories supported a collaboration with Sandia scientists to apply Sandia’s hyperspectral microscope to the study of single molecule imaging and the relation of receptor motion to signaling. Role: PI Sub-award from NIH/NTCNP/Grant 1-U54-RR022241 (PI: A. S. Waggoner, CMU) under the "Driving Biological Projects" mechanism. 8/01/08- 07/31/10 The influence of subunit integrity and TLR4 crosstalk on IgE receptor signaling (Lidke) Single particle tracking of two-color fluorogen activating peptides will be used to monitor IgE stability and IgETLR4 interactions. Role: Co-PI PHS 398/2590 (Rev. 06/09) Page 4 Continuation Format Page