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:

 Sivaramakrishnan S, Schneider JL, Sitikov A, Goldman RD and Ridge KM. (2009) Shear stress induced reorganization of the keratin intermediate filament network requires phosphorylation of K18Ser33 via PKC z and 14-3-3.  Mol Biol Cell  ;Apr 8: epub.  PMID 19357195

Shimi T, Pfleghaar K, Kojima SI, Pack CG, Solivei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T and Goldman RD.  (2008) The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription.  Genes Dev  22:3409-3421.   PMID 19141474  PMCID: PMC2607069

Shumaker DK,  Solimando L,  Sengupta K,  Adam SA,  Grunwald A, Strelkov S,  Aebi U, Cardoso MC and Goldman RD. (2008) The Highly conserved nuclear lamin Ig-fold binds to PCNA: its role in DNA replication.  J Cell Biol  ;Apr 21;181(2):269-80.   PMID 18426975   PMCID: PMC2315674

Adam SA, Sengupta K and Goldman RD. (2008) Regulation of nuclear lamin polymerization by importin α [alpha].  J Biol Chem;Mar 28;283:8462-8468.  PMID 18227062   PMCID: PMC2417177

Sivaramakrishnan SI,  DeGiulio JV, Lorand L, Goldman RD and Ridge KM. (2008)  Micromechanical properties of keratin intermediate filament networks.  PNAS;Jan 22:105(3):889-894.  PMID 18199836   PMCID: PMC2242724

Dechat T,  Shimi T,  Adam SA, Rusinol A, Andres DA, Spielmann HP, Sinensky MS and Goldman RD. (2007) Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging.  PNAS;104(12):4955-60.  PMID 17360326   PMCID: PMC1829246

Kural C,  Serpinskaya AS, Chou YH,  Goldman RD,  Gelfand VI and Selvin PR. (2007) Tracking melanosomes inside a cell to study their molecular motors and their interaction.  PNAS  ;104(13):5378-5382.  PMID 17369356   PMCID: PMC1838505

 

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