Jeffrey Ross, M.D.

Professor of Oncology

B.A., 1965, Biology, Princeton University
M.D., 1969, Medicine, Washington University, St. Louis
Postdoctoral research: National Institutes of Health

Office: 625 McArdle Laboratory
Telephone: Office - (608) 262-3413; Lab - (608) 263-4767
Email: ross@oncology.wisc.edu

Research Interests: Regulation of mRNA stability in mammalian cells

Research Description: Our laboratory studies how messenger RNA turnover influences gene expression and how mRNA-binding proteins influence mRNA translation and stability. The role of mRNA stability in cell biology is important, because the expression of many genes is controlled more by the rate at which their mRNAs are degraded than by the rate at which the genes are transcribed. We developed a cell-free system for studying mRNA turnover and are using the system to characterize the enzymes that degrade mRNAs, the pathways for mRNA degradation, and, most importantly, the regulation of mRNA turnover rates as a function of cell growth, differentiation, and neoplastic transformation. Using the system, we have made the following observations: (1) A protein encoded by Herpes simplex virus causes global destruction of mRNA in infected cells. The protein does not affect rRNA or tRNA. (2) A protein binds to the c-myc mRNA coding region and protects the mRNA from an endoribonuclease. This protein is overexpressed in human colon, lung, and breast cancers. Future studies will focus on the following: (1) Analyze how the Herpes mRNA-destabilizing protein functions. Why and how does it induce mRNA degradation without affecting tRNA or rRNA? (2) Assess the role of the c-myc mRNA-binding protein in cancer. Can this protein be used clinically to detect cancer? The protein induces breast cancer in transgenic mice. What is the mechanism of the transformation process?

Selected recent publications

Mao, C., Flavin, K. G., Wang, S., Dodson, R., Ross, J., and Shapiro, D. J.  Analysis of RNA-protein Interactions by a Microplate-based Fluorescence Anisotropy Assay.  Anal. Biochem., 350:  222-232, 2006.

Noubissi, F. K., Elcheva, I., Bhatia, N., Shakoori, A., Ougolkov, A., Liu, J., Minamoto, T., Ross, J., Fuchs, S. Y., and Spiegelman, V. S.  CRD-BP Mediates Stabilization of bTrCP1 and c-myc mRNA in Response to b-catenin Signalling.  Nature, 441:  898-901, 2006.

Tessier, C. R., Doyle, G. A., Clark, B. A., Pitot, H. C., and Ross, J. Mammary Tumor Induction in Transgenic Mice Expressing an RNA-Binding Protein. Cancer Res., 64: 209-214, 2004.

Lemm, I., and Ross, J. Regulation of c-myc mRNA Decay by Translational Pausing in a Coding Region Instability Determinant. Mol. Cell. Biol., 22: 3959-3969, 2002.

Ross, J., Lemm, I., and Berberet, B. Overexpression of an mRNA-binding Protein in Human Colorectal Cancer. Oncogene, 20: 6544-6550, 2001.

Doyle, G. A., Bourdeau-Heller, J. M., Coulthard, S., Meisner, L. F., and Ross, J. Amplification in Human Breast Cancer of a Gene Encoding a c-myc mRNA-binding Protein. Cancer Res., 60: 2756-2759, 2000.

Ross, J. Structure and Function of the Gene. In: M. D. Abeloff, J. O. Armitage, A. S. Lichter, and J. E. Niederhuber (Eds.), Clinical Oncology, 2nd ed., Chap. 1, pp. 3-9. Philadelphia: W. B. Saunders, 2000.

Ross, J. Assays for Analyzing Exonucleases in Vitro. Methods (Orlando), 17: 52-59, 1999.

Ross, J. Messenger RNA Turnover in Cell-Free Extracts from Higher Eukaryotes. Methods Mol. Biol., 118: 459-476, 1999.

Doyle, G. A. R., Betz, N. A., Leeds, P. F., Fleisig, A. J., Prokipcak, R. D., and Ross, J. The c-myc Coding Region Determinant-binding Protein: A Member of a Family of KH Domain RNA-binding Proteins. Nucleic Acids Res., 26: 5036-5044, 1998.

Lee, C. H., Leeds, P., and Ross, J. Purification and Characterization of a Polysome-associated Endoribonuclease That Degrades c-myc mRNA in Vitro. J. Biol. Chem., 273: 25261-25271, 1998.

Leeds, P., Kren, B. T., Boylan, J. M., Betz, N. A., Steer, C. J., Gruppuso, P. A., and Ross, J. Developmental Regulation of CRD-BP, an RNA-binding Protein that Stabilizes c-myc mRNA in Vitro. Oncogene, 14: 1279-1286, 1997.

Zelus, B. D., Stewart, R. S., and Ross, J. The Virion Host Shutoff Protein of Herpes Simplex Virus Type 1: Messenger Ribonucleolytic Activity In Vitro. J. Virol., 70: 2411-2419, 1996.

Herrick, D. J., and Ross, J. The Half-Life of c-myc mRNA in Growing and Serum-stimulated Cells: Influence of the Coding and 3' Untranslated Regions and Role of Ribosome Translocation. Mol. Cell. Biol., 14: 2119- 2128, 1994.