Postdoctoral Position Available

Lab Page Link

Yu-Li Wang, Ph.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Physiology

Other Affiliation(s):
   Cell Biology
   Cell Dynamics Group
   Interdisciplinary Graduate Program

The Mechanism of Cell Migration and Cell Division

Cell migration and cell division are critical to both pathological conditions such as cancer, and physiological processes such as immune responses and tissue formation.  Both involve complex, transient interactions between the cytoskeleton and signal transduction pathways, and neither can be understood without addressing the “when” and “where” of protein-protein interactions in living cells.

This laboratory applies interdisciplinary approaches to understand the mechanisms of mammalian cell migration and cell division.  The experiments use digital imaging in combination with gene manipulation, pharmacological, and biophysical manipulations to probe molecular activities in single living cells.  Current interests include the mechanism of cytoplasmic protrusion, the generation of traction forces, the guidance of cell migration, the characteristics of cancer cell migration and metastasis, the role of matrix metalloproteinases and tyrosine kinases, the coordination between cytokinesis and mitosis, the mechanism of membrane ingression during cytokinesis, and the dynamics of cell cortex and microtubules during cell division.

Representative Publications (student publications highlighted):

Wheatley, S.P., O’Connell, C.B. and Wang, Y.-L. (1998) Inhibition of chromosomal separation provides insights into cleavage furrow stimulation in cultured epithelial cells.  Mol. Bio. Cell 9:2173-2184.

Wang, Y.-L. (1998) Digital deconvolution of fluorescence images for biologists.  Methods Cell Biol. 56:305-315.

Wheatley, S.P. and Wang, Y.-L. (1998) Fluorescence immunolocalization.  Methods Cell Biol. 57:313-332.

Wang, Y.-L. and Pelham, R. J. Jr. (1998) Preparation of a flexible, porous polyacrylamide substrate for mechanical studies of cultured cells.   Methods Enzymol 298: 489-496.

O’Connell, C.B., Wheatley, S.P., Ahmed, S. and Wang, Y.-L. (1999) The small GTP-binding protein Rho regulates cortical activities in cultured cells during division.  J. Cell Biol. 144:305-313.

Dembo, M. and Wang, Y.-L. (1999) Stresses at the cell-to-substrate interface during locomotion of fibroblasts.  Biophys. J. 76:2307-2316.

Pelham, R.J. Jr. and Wang, Y.-L. (1999) High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate.   Mol. Biol. Cell 10:935-945.

O'Connell, C.B. and Wang, Y.-L. (2000) Mammalian spindle orientation and position respond to changes in cell shape in a dynein-dependent fashion.   Mol. Biol. Cell 11:1765-1774.

Lo, C.-M., Wang, H.-B., Dembo, M. and Wang, Y.-L. (2000) Cell movement is guided by the rigidity of the substrates.  Biophys. J. 79:144-152.

Kaverina, I., Krylyshkina, O., Gimona, M., Beningo, K., Wang, Y.-L. and Small, J.V. (2000) Enforced polarization and locomotion of fibroblasts lacking microtubules. Curr. Biol. 10:739-742.

Wang, H.-B., Dembo, M. and Wang, Y.-L. (2000) Substrate flexibility regulates growth and apoptosis of normal but not transformed cells.  Am. J. Physiol. 279:C1345-C1350.

Faulkner, N.E., Dujardin, D.L., Tai, C.Y., Vaughan, K.T., O'Connell, C.B., Wang Y.-L. and Vallee, R.B. (2000) A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function.  Nature Cell Biol. 2:784-791.

Munevar, S., Dembo, M. and Wang, Y.-L. (2001) Traction force microscopy of normal and transformed fibroblasts.  Biophys. J. 80:1744-1757.

O'Connell, C.B., Warner, A.K. and Wang, Y.-L. (2001) Distinct roles of the equatorial and polar cortices in the cleavage of adherent cells.  Curr. Biol. 11:702-707.

Beningo, K.A., Dembo, M., Kaverina, I., Small, J.V. and Wang, Y.-L. (2001) Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts.  J. Cell Biol. 153:881-887.

Wang, H.-B., Dembo, M., Hanks, S.K. and Wang, Y.-L. (2001) Focal adhesion kinase is involved in mechanosensing during fibroblast migration.  Proc. Natl. Acad. Sci. USA 98:11295-11300.

Menevar, S., Wang, Y.-L. and Dembo, M. (2001) Distinct roles of frontal and rear cell-substrate adhesions in fibroblast migration.  Mol. Biol. Cell. 12:3847-3954.

Wang, Y.-L. (2001) The mechanism of cytokinesis: reconsideration and reconciliation.  Cell Struct. Funct. 26:633-638.

Beningo, K.A. and Wang, Y.-L. (2002) Flexible substrata for the detection of traction forces.  Trends Cell Biol. 12:79-84.

Beningo, K.A. and Wang, Y.-L. (2002) Fc-receptor mediated phagocytosis is regulated by mechanical properties of the target.  J. Cell Sci. 115:849-856.

Kaverina, I., Krylyshkina, O., Beningo, K., Anderson, K., Wang, Y.-L. and Small, J.V. (2002) Tensile stress stimulates microtubule outgrowth in living cells.  J. Cell Sci. 115:2283-2291.

Murata-Hori, M., Tatsuka, M. and Wang, Y.-L. (2002) Probing the dynamics and functions of aurara B kinase in living cells during mitosis and cytokinesis.  Mol. Biol. Cell 13:1099-1108.

Murata-Hori, M. and Wang, Y.-L. (2002) The kinase activity of aurora B is required for kinetochore-microtubule interactions, bi-directional chromosomal movements, and spindle microtubule organization during mitosis.  Curr. Biol. 12:894-899.

Murata-Hori, M. and Wang, Y.-L. (2002) Both Midzone and Astral Microtubules Are Involved in the Delivery of Cytokinesis Signals to the Equatorial Cortex: Insights from the Mobility of Aurora B.   J. Cell Biol. 159:45-53.

Beningo, K.A., Lo, C.-M. and Wang, Y.-L. (2002) Flexible polyacrylamide substrata for the analysis of mechanical interactions at cell-substratum adhesions.   Methods Cell Biol. 69:325-339.

Marganski, W.A., Dembo, M. and Wang, Y.-L. (2003) Measurements of cell-generated deformations on flexible substrata using correlation-based optical flow.  Methods Enzymol. 361:197-211.

Wang, Y.-L. (2003) Computational restoration of fluorescence images: noise reduction, deconvolution, and pattern recognition.  Methods Cell Biol. 72:337-348.

Munevar, S., Wang, Y.-L. and Dembo, M. (2004) Regulation of mechanical interactions between fibroblasts and the substrate by stretch-activated calcium entry.  J. Cell Sci. 117 :85-92.

Lo, C.-M., Buxton, D.B., Chua G.C., Dembo, M., Adelstein, R.S., and Wang, Y.-L. (2004) Nonmuscle myosin IIB is involved in the guidance of fibroblast migration.  Mol. Biol. Cell. 15:982-989.

Potential Rotation Projects

The laboratory combines biological, chemical, and physical approaches to investigate a wide range of questions related to cell migration and cell division.  The general emphasis is to detect and probe molecular functions in living cells by microscopy.  Described below is the general scope of research for graduate students.  Projects are typically determined taking into consideration students’ background, interests, and future goals.

Area #1: The mechanism of cell migration.  Cell migration involves complex crosstalks between signal transduction pathways and the cytoskeleton.  The project will use model systems developed in this laboratory to investigate normal or cancerous cell migration in a tissue-like environment.  The trainee may apply our unique techniques to image mechanical forces exerted by migrating cells, or to probe cellular responses to mechanical stimulations.  Experiments will be performed with living cells transfected with various GFP probes.  Functions of specific signaling pathways in guiding cell migration will be investigated by gene manipulation or pharmacological approaches combined with live cell imaging.

Area #2: The mechanism of cell division. Cytokinesis, the final step in cell division causing a cell to pinch into two, involves close coordination between cortical ingression and chromosomal separation.  The project will use 2-D, 3-D or 4-D imaging to investigate the dynamics of various structural and signal transduction components.  Experiments will employ GFP technology, molecular biological, chemical, and physical manipulations, and photobleaching, photactivation, and photoablation approaches, to probe the mechanism of ingression and the function of regulatory pathways during cytokinesis

Academic Background

Yu-li Wang received his B.S. in Physics from National Taiwan University in 1973, and Ph.D. in Biophysics from Harvard University in 1980.  He became a Staff Scientist of the National Jewish Medical and Research Center in Denver, CO, in 1982, and moved to the Worcester Foundation for Biomedical Research in 1987 as a Senior Scientist and later promoted to Principal Scientist.  He joined the Department of Physiology when Worcester Foundation merged with University of Massachusetts Medical School in 1997.  Yu-li Wang has served in a number of grant reviewing panels at NIH and is currently a member of the National Advisory General Medical Sciences Council.  He is the recipient of a NIH MERIT Award in 1998.

Special Equipment

This is an equipment-intensive laboratory.  A high ratio of equipment to personnel is maintained to ensure maximal productivity.

Six research fluorescence microscopes, each equipped with a low-light CCD camera, computer image processor, and computerized focusing control for auto-focusing and single-cell tomography.

Hardware and software for image deconvolution, 3D reconstruction, and traction force imaging.

Total internal reflection fluorescence optics.

One spinning-disk and one laser scanning confocal microscope.

Micropipet puller, microforge, and four micromanipulators, for microinjection, micromanipulation and high resolution single-cell pharmacological analysis.

High power argon ion laser for photobleaching.

Nitrogen laser for photoablation and photoacvitation.

Office: Biotech IV, Suite 327
Phone: 508-856-8781
E-mail: Yu-Li.Wang.Forward@umassmed.edu
Keywords: Cell Migration, Cell Dynamics, Biomedical Engineering, Mitosis, Imaging and Microscopy

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Wang for additional details.