Assistant Professor, Department of Anatomy & Structural Biology
Spatiotemporal Dynamics of Rho-family GTPases in living cells, visualized by fluorescent biosensors.
P21 Rho family small GTPases are critically important in many disease processes including malignant cancers, developmental defects, arthrosclerosis and autoimmune dysfunction. This class of signaling molecules is critical in these diseases by impacting directly: cell polarity, motility and migration through their actions on downstream cytoskeleton/adhesion dynamics; and proliferation by intersecting mitogenic and apoptotic signaling pathways. Rho family GTPases regulate these processes by tightly coordinating their activities in response to various environmental cues. Only a very small fraction of GTPases turn on or off at different locations at different times to produce specific effects. Furthermore, most Rho GTPases exist in an interdependent cascade of activation/inhibition pathways resulting in a tight coordination of activation dynamics between each other. It is this coordination of multiple GTPases that is thought to regulate a variety of cellular signaling outcomes. However it has been difficult if not impossible to dissect the spatiotemporal dynamics of signal regulation by conventional imaging or biochemical techniques.
My primary research interest is the development of fluorescent biosensors to visualize and decipher these complex spatiotemporal dynamics of protein activations in living cells in real time. These biosensors enable direct visualization of the spatiotemporal dynamics of protein signaling pathways at high resolution, previously inaccessible by traditional biochemical methods. Knowledge gained from these studies will open a new window into previously unseen, coordinated mechanisms of GTPase signal regulation.
FRET biosensor for RhoA GTPase (Pertz, Hodgson et al. 2006 Nature)
Above FRET biosensor used in living fibroblasts. LEFT: Ratio activity indicating RhoA activation. Warm colors correspond to regions of high-activity. RIGHT: Acceptor emission indicating localization of biosensor in the cell. (2006 Nature)
Price, J. H., Goodacre, A., Hahn, K. M., Hodgson, L., Hunter, E. A., Krajewski, S., Murphy, R. F., Rabinovich, A., Reed, J. C., and Heynen, S. (2002) “Advances in Molecular Labeling, High Throughput Imaging and Machine Intelligence Portend Powerful Functional Cellular Biochemistry Tools”. J. Cell. Biochem.: Suppl. 39; 194-210.
Nalbant, P.*, Hodgson, L.*, Kraynov, V., Toutchkine, A., and Hahn, K. M. (2004) “Active Dynamics of Endogenous Cdc42 Visualized in Living Cells”. Science: Vol. 305(5690); 1615-1619. *authors contributed equally.
Hodgson, L., Nalbant, P., Shen, F., and Hahn, K. (2006) “Imaging and Photo-bleach Correction of Mero-CBD: Sensor for Endogenous Cdc42 Activation”. Methods in Enzymology: Vol. 406; 140-156: Editor Alan Hall, Elsevier, Inc., New York.
Pertz, O., Hodgson, L., Klemke, R. L., and Hahn, K. M. (2006) “Spatio-temporal Analysis of RhoA Activity in Cell Migration”. Nature: Vol. 440; 1069-72.
Shen, F., Hodgson, L., Rabinovitch, A., Pertz, O., Hahn, K., and Price, J. H. (2006) “Functional Proteometrics for Cell Migration”. Cytometry: Vol. 89A; 563-572.
Shen, F., Hodgson, L., and Hahn, K. (2006) “Digital Autofocus Methods for Automated Microscopy”. Methods in Enzymology: Vol. 414; 620-632, Elsevier, Inc., New York.
Hodgson, L., Chan, E., Hahn, K., and Yousaf, M. (2007) “Combining Surface Chemistry with a FRET-based Biosensor to Study the Dynamics of RhoA GTPase Activations in Cells on Patterned Substrates”. Journal of American Chemical Society: Vol. 129(30), 9264 -9265.
Healy, K. D., Hodgson, L., Kim, T. Y., Shutes, A., Maddileti, S., Juliano, R. L., Hahn, K. M., Harden, T.K., Bang, Y. J., and Der, C. J. (2008) “DLC-1 Suppresses Non-small Cell Lung Cancer Growth and Invasion by RhoGAP-dependent and Independent Mechanisms.”: Molecular Carcinogenesis: Vol. 47(5), 326-7.
Garrett, S., Hodgson, L., Rybin, A., Toutchkine, A., Hahn, K., Lawrence, D., and Bresnick, A. (2008) “A Biosensor of S100A4 Metastasis Factor Activation ¬ Inhibitor Screening and Cellular Activation Dynamics”: Biochemistry: Vol. 47(3), 986-996.
Hodgson, L., Pertz, O., and Hahn, K. (2008) “Optimization of fluorescent protein biosensors based on protein-ligand interactions”. Methods in Cell Biology: Vol. 85, 63-81.
Shen, F., Hodgson, L., Price, J. H., and Hahn, K. M. (2008) “Digital Differential Interference Contrast Autofocus for High-Resolution Oil-Immersion Microscopy”. (2008) Cytometry: Vol. 73(7), 658-66.
Hodgson, L. (2008) “New approaches to in-cell detection of protein activity: genetically encoded chemiluminescence probes pave the way to robust HTS assays”. JACS Chemical Biology: Vol. 3(6), 335-7.
Machacek, M.*, Hodgson, L.*, Welch, C.*, Elliott, H., Nalbant, P., Pertz, O., Abell, A., Johnson, G., Hahn, K., and Danuser, G. (2009) “Coordination of Rho GTPase activation during protrusion”. Nature: Vol. 461, 99-103. * authors contributed equally.
Hodgson, L., Shen, F., and Hahn, K. (2010) “Measuring Dynamic Changes in Rho-family GTPases in Living Cells”. Curr Protoc Cell Biol.;Chapter 14:Unit 14.11.1-26.
Spiering, C. D. and Hodgson, L. (2011) “Dynamics of Rho-family small GTPases in actin regulation and motility”. Cell Adhesion & Migration: Vol. 5(2), 1-11.
Bravo-Cordero, J. J., Oser, M., Chen, X., Eddy, R., Hodgson, L. and Condeelis, J. (2011) “A novel spatiotemporal RhoC activation pathway locally regulates cofilin activity at invadopodia”. Current Biology: .Vol. 21(8), 635-44.
Spiering, C. D. and Hodgson, L. (2011) “Multiplex Imaging of Rho family GTPase Activities in Living Cells”. Methods in Molecular Biology: In Press.
Bravo-Cordero, J. J., Hodgson, L., and Condeelis, J. (2011) “Directed Cell Migration and Invasion During Metastasis”. Current Opinion in Cell Biology: Accepted for publication.
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Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 217
Bronx, NY 10461