Robert D. Goldman
Rank: Stephen Walter Ranson Professor and Chair
Brief description of research area: Structure and Function of Cytoskeletal Systems
Degree: Ph.D.
Institution degree obtained from: Princeton University
Voice: 312.503.4215
Fax: 312.503.7912
E-mail: r-goldman@northwestern.edu

Detailed research description:
Our research focuses on the structure and function of cytoskeletal systems, particularly the intermediate filament (IF) system in fibroblasts, epithelial cells, and nerve cells. IFs are composed of large families of proteins that vary in composition from one cell type to another--even among cells in the same tissue. Using a variety of techniques, we have demonstrated that IFs form elaborate networks that course throughout the cytoplasm and establish connections with both the nuclear and cell surfaces.

At the nuclear surface, they are linked either directly or indirectly with the nuclear lamins, which are chromatin-associated IF protein family members. At the level of the plasma membrane, IFs are involved as cytoskeletal linkages to the focal adhesion of fibroblasts and the desmosomes and hemidesmosomes of epithelial cells. Throughout the cytoplasm, we have shown that IFs are associated with the other cytoskeletal elements, such as microtubules and microfilaments.

Our approach to studying the IF system involves biochemical, morphological, immunological, cell physiological, and molecular techniques. Our hypothesis is that the IF system forms a continuous network linking the nuclear and cell surfaces, functioning in such diverse activities as the establishment and maintenance of cell shape, organelle movements within the cytoplasm, nuclear positioning, nuclear-cytoplasmic interactions, and signal transduction.

Since many human diseases have been linked to changes in cytoskeletal IF systems, we are also developing models to study the mechanisms involved in IF alterations in various diseases. One example is amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) in which we have been able to induce neurofibrillary tangles to form in single cultured nerve cells. These tangles are similar to those found in ALS neurons. Therefore, we are able to study the effects of neurofilament tangle formation in single cells. During the summer, researchers from this laboratory also conduct studies on the mechanisms of chromatin/nuclear envelope interactions in eggs of the surf clam at the Marine Biological Laboratory in Woods Hole.

Representative publications:

 Tsai, M-Y., Wang, S., Heidinger, J., Shumaker, D.K., Adam, S.A., 

    Goldman, R.D., Zheng, Y.  Requirement of a lamin B matrix induced by

    RanGTP for mitotic spindle assembly. Science. 2006 Mar 31;

    311(5769):1887-93.

 

Chang L, Shav-Tal Y., Trcek T., Singer R.H., Goldman R.D. Assembling an

    intermediate filament network by dynamic cotranslation. J Cell Biol.

    2006 Feb; 172(5):747-58.

 

Helfand B.T., Chou Y.H., Shumaker D.K., Goldman R.D. Intermediate

    filament proteins participate in signal transduction. Trends in Cell Biol.

    2005 Nov; 15(11):568-70.

 

Shumaker, D.K., Lopez-Soler, R.I., Adam, S., Herrmann, H., Moir, R.D.,

    Spann, T.P., Goldman, R.D. Functions and Dysfunctions of the Lamin

    A Ig-fold Domain: Nuclear Assembly, Growth and Emery-Dreifuss

    Muscular Dystrophy. PNAS (USA). 2005 Oct; 102:15494-15499.

 

Ridge K.M., Linz L., Flitney F.W., Kuczmarski E.R., Chou YH, Omary M.B.,

    Sznajder J.I., Goldman R.D. Keratin 8 phosphorylation by protein

    kinase C delta regulates shear stress-mediated disassembly of keratin

    intermediate filaments in alveolar epithelial cells.

    J Biol Chem. 2005 Aug; 280(34):30400-5.

 

Goldman R.D., Spector D.L. Basic Methods in Microscopy: Protocols and

    Concepts from "Cells: A Laboratory Manual". Cold Spring Harbor

    Laboratory Press. 2005

 

(click images to enlarge)