Department Affiliation: Primary: Urology; Secondary: Oncology; Pharmacology and Molecular Sciences; Pathology
Degree: Ph.D., Johns Hopkins University
Telephone Number: 410-955-2517
Fax Number: 410-614-8096
School of Medicine Address: 143 Jefferson Street Building, 600 N. Wolfe St., Baltimore, MD 21287-2101
Nuclear structure and DNA organization in normal and cancer cells; mechanism of androgen action on prostate cells
Disorganization in nuclear size and shape is a hallmark of the cancer cell. Our research is focused on understanding the role of nuclear structure and DNA organization and function. This laboratory was the first to describe a nuclear scaffold system, termed the nuclear matrix, that determines the shape of the nucleus and provides a 3-dimensional lattice for organizing the DNA into specific functional units. The nuclear matrix is a residual framework structure that organizes 50,000 loop domains of DNA of approximately 60 kilobase lengths each, and during replication the loops are reeled through fixed replicating sites attached to the nuclear matrix. Changes in the nuclear matrix structure and composition are probably related to changes in nuclear function. The nuclear matrix determines the shape of the nucleus, and it is believed that a clear understanding of this structure and its chemo-mechanical properties will be of importance. The nucleus matrix is the central part of an overall tissue matrix network that extends from the extracellular matrix through the cytoskeleton and connects to the nuclear matrix. Studies are underway to delineate how these interconnecting matrix structures interact and alter the function of each component.
Our laboratory also studies the mechanism of action of androgens in inducing prostate growth and gene function. Steroid hormone receptors bind to the nuclear matrix and are brought into close proximity for interactions with hormone responsive sequences on induced genes. Active genes are bound to the nuclear matrix in a tissue specific manner. The composition of the nuclear matrix is tissue specific. The 3-dimensional organization of DNA is different for each cell type and this organization is determined by the composition of the nuclear matrix.
We are assessing the role of chaos, fractals and complexity in the self-organization of DNA, cells and tissue in relation to tumor biology.
- Getzenberg, R.H., Pienta, K.J., Ward, S.W., and Coffey, D.S. Nuclear structure and the three-dimensional organization of DNA. J. Cell Biochem. 47:289-299, 1991. Pub Med Reference
- Luke, M.C. and Coffey, D.S. Human androgen receptor binding to the androgen response elements of prostate specific antigen. J. Andrology 15:41-51, 1994. Pub Med Reference
- Sommerfeld, H.J., Meeker, A.K., Piatyszek, M.A., Bova, G.S., Shay, J.W., and Coffey, D.S. Telomerase activity: A prevalent marker of malignant human prostate tissue. Cancer Res. 56:218-222, 1996. Pub Med Reference
- Posadas, E.M., Criley, S.R., and Coffey, D.S. Chaotic oscillations in cultured cells: Rat prostate cancer. Cancer Research 56:3682-3688, 1996. Pub Med Reference
- Coffey, D.S. Self organization, complexity and chaos: The new biology for medicine, Nature Medicine 4:882-885, 1998. Pub Med Reference
- DeMarzo, A.M., Nelson, W.G., Meeker, A.K., and Coffey, D.S. Stem cell features of benign and malignant prostate epithelial cells, J. Urol. 160:2381-2392, 1998. Pub Med Reference
- Takaha, N., Resar, L.M., Vindivich, D., and Coffey, D. S. High Mobility Group Protein HMGI (Y) Enhances Tumor Cell Growth, Invasion, and Matrix Metalloproteinase-2 Expression in Prostate Cancer Cells. Prostate 60:160-167, 2004. Pub Med Reference
- Coffey, D.S., Getzenberg, R.H., and DeWeese, T.L. Hyperthermic Biology and Cancer Therapies. A Hypothesis for the "Lance Armstrong Effect". JAMA 296:445-448, 2006. Pub Med Reference
Other graduate programs in which Dr. Coffey participates: