Research Interests
Research in this laboratory encompasses several projects. We have a longstanding effort aimed at developing and characterizing fluorescent probes of membrane potential. Although this effort is continuing, we are now particularly focused on studies of the non-linear optical properties of the dyes, including second harmonic generation as an alternative to fluorescence as a probe of membrane potential. A second project is aimed at elucidating how electrical potentials may vary along neuronal surfaces and the cell physiological consequences of such heterogeneities. Among the consequences that have been suggested by our studies are directed neurite outgrowth and local sensitization of voltage-dependent ion channels. Quantitative digital imaging microscopy is combined with patch clamp recording in these studies and has revealed roles for intracellular calcium changes in the mechanisms of these phenomena. Finally, we are very excited about a project called the "Virtual Cell", in which we have created a framework for using computer simulation to explore cell biological mechanisms. The models are built naturally from experimental images of cell and subcellular structures combined with biochemical and electrophysiological data. Among the published ways we have used the “Virtual Cell” system are to explain the pattern of cytosolic calcium waves evoked by hormonal stimulation of a neuronal cell and the regulation of nucleocytoplasmic transport.
Selected Publications
Ditlev, J.A., N.M. Vacanti, I.L. Novak, and L.M. Loew. 2009. An open model of actin dendritic nucleation. Biophys J. 96:3529-3542.
Brown, S., F. Morgan, J. Watras, and L.M. Loew. 2008. Analysis of phosphatidylinositol-4,5-bisphosphate signaling in cerebellar Purkinje spines. Biophys J. 95:1795-1812.
Kee, M.Z., J.P. Wuskell, L.M. Loew, G.J. Augustine, and Y. Sekino. 2008. Imaging activity of neuronal populations with new long-wavelength voltage-sensitive dyes. Brain Cell Biol. 36:57-72.
Moraru, I.I., J.C. Schaff, B.M. Slepchenko, M. Blinov, F. Morgan, A. Lakshminarayana, F. Gao, Y. Li, and L.M. Loew. 2008. The virtual cell modeling and simulation software environment. IET Systems Biology. 2:352-362.
Yan, P., A. Xie, M.-d. Wei, and L.M. Loew. 2008. Amino(oligo)thiophene-based Environmentally Sensitive Biomembrane Chromophores. Journal of Organic Chemistry. 73:6587-6594.
Honors, Awards, and Professional Activities
Phi Beta Kappa; NSF Trainee, 1969-73, Nehemiah Gittelson Medal; NIH Research Career Development Award, 1980-85; American Chemical Society; Biophysical Society; AAAS. Editorial Boards: Biophysical Journal, Journal of Fluorescence, Cell Biophysics & Biochemistry; Chair NIH MABS Study Section, 2004-2006; Boehringer Ingelheim Chair in Cell Sciences, 2007 - ; Elected to Connecticut Academy of Science and Engineering, 2008.
Patents Sapia, M. A., J. C. Schaff, I. R. Greenshields, L. M. Loew, and F. R. Morgan (2000) “Method and apparatus for three-dimensional deconvolution of optical microscope images,” United States Patent 6,166,853.
Schaff, J. C., J. Carson and L. M. Loew (2001) “Method and apparatus for modeling cell structure and function,” United States Patent 6,219,440.
Schaff, J. C., J. Carson and L. M. Loew (2004) “Method for modeling cellular structure and function,” United States Patent 6,708,141 |