PHD, 1986, University of California B.S., 1977, California State University
Relevant Publications
Coffman, F.D., He, M., Diaz, M.-L. and Cohen, S. DNA replication initiates at different sites in early and late S phase within human ribosomal RNA genes. Cell Cycle 4(9): 1223-1226, 2005.
Coffman, F.D., He, M., Diaz, M.-L. and Cohen, S. Multiple initiation sites within the human ribosomal RNA gene. Cell Cycle 5(11): 1223-33 2006.
Scaglione, B., Salerno, E., Balan, M., Coffman, F., Landgraf, P., Abbasi, F., Kotenko, S., Marti, G. and Raveche E.S. (2007). Murine models of CLL: role of microRNA-16 in the NZB mouse model. Brit. J. Haematol 139: 645-657
Kim, S.H., Das, K., Noreen, S., Coffman, F. and Hameed, M. Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer. World Journal of Surgical Oncology 5:17 (2007).
de la Fuente C. Wang L. Wang D. Deng L. Wu K. Li H. Stein LD. Denny T. Coffman F. Kehn K. Baylor S. Maddukuri A. Pumfery A. Kashanchi F. Paradoxical effects of a stress signal on pro- and anti-apoptotic machinery in HTLV-1 Tax expressing cells. Mol. Cell. Biochem. 245(1-2):99-113, 2003.
Areas Of Interest
I. Initiation of DNA replication in normal and transformed human cells.
DNA replication in most human cells initiates within genetically conserved DNA sequences termed replication origin regions. Within these origin regions, replication initiates at one of several potential initiation sites, and which site is used depends upon chromatin conformation and local gene expression. This ability to select one site out of several possible sites is believed to provide conformational flexibility to the nucleus during processes that significantly change gene expression, such as activation and differentiation. Our studies focus on a replication origin region from the human ribosomal RNA gene, and most of this origin is contained within a 7 kb cloned sequence. We have identified several preferred initiation sites within this region, and that replication begins at different sites in early and late S phase. We are investigating protein binding to this region, origin localization during the cell cycle, and if the same initiation sites are used in normal cells and cancer cells, as errors in replication initiation can lead to the types of mutations seen in human tumors.
II. Modulation of tumor cell apoptosis by TNF family ligands
The cytokine tumor necrosis factor (TNF) and members of the TNF family initiate apoptosis in a number of tumor cell lines, and some chemotherapeutic agents can greatly enhance the sensitivity of these cells to TNF cytotoxicity. Two DNA topoisomerase II inhibitors that are used as clinical anticancer agents, the epipodophyllotoxins VP-16 and VM-26, synergistically enhance the sensitivity of tumor cell lines to the cytotoxic activity of TNF. We are currently examining the NF-kB and JNK pathways in this system, as they can both be activated by TNF, and one pathway promotes apoptosis (JNK) and one pathway promotes cell survival (NF-kB). We are also investigating potential enhancement of tumor cell killing by other TNF family ligands such as fas and TRAIL, as they do not mediate sepsis and may have greater clinical applicability.
III. Chitinase family proteins in human cancers
Our laboratory is part of a large group investigating alterations in gene expression that accompany the development of high grade soft tissue sarcomas. Soft tissue sarcomas represent a small percentage of tumors diagnosed on a yearly basis in the United States, but prognosis is poor for high grade tumors and a significant percentage of cases result in patient mortality. Identification of genes that are significantly up or down regulated during high grade tumor development would provide useful markers for diagnosis and prognosis, and possibly define proteins or pathways amenable to therapeutic intervention. Surgical samples of tumors and surrounding tissue are graded by surgical pathologists, and high grade tumor, low grade tumor, and normal tissue samples are sent for microarray gene expression analysis. The initial stages of this collaborative project have identified a number of genes that appear consistently upregulated or downregulated in high grade soft tissue sarcomas. One group that shows initial promise is the chitinase family of proteins, several of which have been found to be upregulated in patients with breast cancer, colon cancer, malignant glioma, rheumatoid arthritis, and Gaucher's Disease.
