Research Interests:

Introduction: Cytoskeleton, Nuclear Matrix and Chromatin
Aberrant nuclear and cellular structures are hallmarks of malignant transformation. Thus it is not surprising that the three-dimensional structure of the cell both affects and is affected by changes in gene expression. Our research investigates the role of the cytoskeleton, nuclear matrix, and chromatin structure in the genesis of cancer. The shape of a cell is governed by a dynamic tissue matrix, which includes extracellular matrix, cytoskeleton and nuclear matrix. Mechanical and chemical signals are transmitted to the nucleus, resulting in alterations in the three-dimensional chromatin organization of genes. The signal transduction pathways affect histone modifications, such as acetylation and phosphorylation, resulting in a relaxed chromatin structure observed in oncogene-transformed cells.

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Nuclear Matrix Proteins and Cancer
Nuclear matrix proteins serve as fingerprints to distinguish normal cells from cancer cells. Of potential importance is the demonstration that nuclear matrix proteins can be detected in the serum and urine of cancer patients. We have shown that oncogene-transformed, highly metastatic mouse cells have gross changes in nuclear shape and that these changes in nuclear shape correlate with alterations in the nuclear matrix proteins.

Nuclear Matrix and Transcription Factors
Transcription factors are associated with the nuclear matrix. It has been proposed that the nuclear matrix recruits transcription factors, facilitating their interaction with regulatory DNA elements. We developed a cisplatin cross-linking procedure to investigate whether nuclear matrix associated transcription factors were bound to nuclear matrix attached DNA in situ in MCF-7 cells.

Lab Members