Observations of living cells or tissues through fluorescence microscopy provide insights into dynamic behavior and cellular physiology that cannot be obtained from observations of fixed specimens. Such information may reveal the pathological state of a tissue to the physician or information on cytoskeletal dynamics to the research scientist. Whole genome sequencing combined with the use of fluorescent protein reporters has opened up the possibility of visualizing the distribution and dynamics of any protein in living tissue. Furthermore, the use of specific fluorescent indicators has allowed the physiological state of a cell to be visualized in vivo. However, problems of overlapping spectra, low signal and light scatter pose serious limitations on what can be achieved in practice with fluorescence microscopy. These problems will be addressed by the development of a multi-photon imaging system that makes maximum use of all the information present in the fluorescence signal. A novel photon-counting detector will be developed that simultaneously measures the wavelength and lifetime of individual fluorescent photons. Algorithms will be developed to analyze and extract physically meaningful characteristics of individual fluorescent components from noise-limited signals. The system will be applied to cell biological studies using fluorescent reporters and to the identification of potentially diagnostic spectral/lifetime signatures of cells and tissue culture models of cancer.
| Conklin, Matthew W; Eickhoff, Jens C; Riching, Kristin M et al. (2011) Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol 178:1221-32 |
| Hall, Gunnsteinn; Spalding, Gabriel C; Campagnola, Paul J et al. (2011) Fast localized wavefront correction using area-mapped phase-shift interferometry. Opt Lett 36:2892-4 |
| Gill, Erin M; Straseski, Joely A; Rasmussen, Cathy A et al. (2010) Visualization of morphological and molecular features associated with chronic ischemia in bioengineered human skin. Microsc Microanal 16:117-31 |
| Skala, Melissa; Ramanujam, Nirmala (2010) Multiphoton redox ratio imaging for metabolic monitoring in vivo. Methods Mol Biol 594:155-62 |
| Provenzano, Paolo P; Eliceiri, Kevin W; Keely, Patricia J (2009) Shining new light on 3D cell motility and the metastatic process. Trends Cell Biol 19:638-48 |
| Provenzano, P P; Inman, D R; Eliceiri, K W et al. (2009) Matrix density-induced mechanoregulation of breast cell phenotype, signaling and gene expression through a FAK-ERK linkage. Oncogene 28:4326-43 |
| Provenzano, Paolo P; Eliceiri, Kevin W; Keely, Patricia J (2009) Multiphoton microscopy and fluorescence lifetime imaging microscopy (FLIM) to monitor metastasis and the tumor microenvironment. Clin Exp Metastasis 26:357-70 |
| Rueden, Curtis T; Conklin, Matthew W; Provenzano, Paolo P et al. (2009) Nonlinear optical microscopy and computational analysis of intrinsic signatures in breast cancer. Conf Proc IEEE Eng Med Biol Soc 2009:4077-80 |
| Gehler, Scott; Baldassarre, Massimiliano; Lad, Yatish et al. (2009) Filamin A-beta1 integrin complex tunes epithelial cell response to matrix tension. Mol Biol Cell 20:3224-38 |
| Provenzano, Paolo P; Inman, David R; Eliceiri, Kevin W et al. (2008) Collagen density promotes mammary tumor initiation and progression. BMC Med 6:11 |
Showing the most recent 10 out of 27 publications
