Jeffrey E. DeClue, Ph.D.

Jeffrey E. DeClue, Ph.D., Principal Investigator

Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health

Building 36, Room 1D-32, National Cancer Institute, Bethesda, MD 20892-4040
Tel 301-496-4732
Fax 301-480-5322

E-mail: decluej@dc37a.nci.nih.gov

Biographical Sketch

Dr. DeClue attended Brown University, and graduated in 1983 with the degree of Sc.B. in Biology. He enrolled at the University of California at Berkeley, and earned a Ph.D. in Zoology in 1988, working in the laboratory of Dr. G. Steven Martin. The focus of his graduate work was the mechanism of transformation by avian retroviruses encoding protein-tyrosine kinases as their oncogenes (e.g., erbB, fps, src). Dr. DeClue joined the National Cancer InstituteŐs Laboratory of Cellular Oncology as a Post-doctoral Fellow in 1989, and began studies on the role of Ras in cell metabolism and transformation. These studies led to an interest in the regulation of Ras and other small GTPases, and their involvement in cell growth regulation and cancer. In 1992, Dr. DeClue served as Visiting Professor at the University of Copenhagen, Denmark for several months. In April 1995, Dr. DeClue began an appointment as Senior Staff Fellow and principal investigator in the Laboratory of Cellular Oncology.

Research Interests

The current research program in the laboratory involves two broad areas: signal transduction involving low molecular weight GTPases such as Ras, and the role of tumor suppressor genes in cell growth regulation and tumorigenesis. As a focus for these studies, we are investigating the molecular pathology of two human genetic diseases: neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). Both conditions predispose affected individuals to the development of benign tumors in a wide variety of organs, and more rarely to malignant tumors. Through a striking molecular parallel the products of the NF1 and TSC2 genes, which are predisposing for NF1 and TSC respectively, both interact with and potentially regulate two different low molecular weight GTPases present in most cells. The protein product of NF1 (designated neurofibromin) acts as a negative regulator of Ras, while the TSC2 product (tuberin) interacts with and may regulate the activity of the closely related Rap1. We are investigating the function and properties of neurofibromin and tuberin to gain a better understanding of their role in normal cell growth, as well as in the pathology of these disorders. Both projects currently involve the use of animal models to study these disorders, in particular through the analysis of cells derived from animals with targeted disruption of NF1 or TSC2. These cells are being used to investigate the signal transduction pathways initiated by Ras and Rap1. In addition, we are carrying out structure/function analyses of NF1 and TSC2 using a variety of assays, including biochemical analyses and assays for the suppression of cell growth.

Representative Publications

  1. Kim, H., Rosenbaum, T., Marchionni, M.A., Ratner, N., and DeClue, J.E.: Schwann cells from neurofibromin deficient mice exhibit activation of p21ras, inhibition of cell proliferation and morphological changes. Oncogene 11: 325-335, 1995.

  2. Wienecke, R., Kšnig, A., and DeClue, J.E.: Identification of tuberin, the tuberous sclerosis- 2 product: tuberin possesses specific Rap1GAP activity. J. Biol. Chem. 270: 16409-16414, 1995.

  3. Jin, F., Wienecke, R., Xiao, G-H., Maize, J.C., DeClue, J.E., and Yeung, R.S.: Suppression of tumorigenicity by the wild-type tuberous sclerosis 2 (TSC2) gene and its C-terminal region. Proc. Natl. Acad. Sci. USA. 93: 9154-9159, 1996.

  4. Wienecke, R., Maize, J.C., Shoarinejad, F., Vass, W.C., Reed, J., Bonifacino, J.S., Resau, J.H., de Gunzburg, J., Yeung, R.S., and DeClue, J.E.: Co-localization of the TSC2 product tuberin with its target Rap1 in the Golgi apparatus. Oncogene 13: 913-923, 1996.

  5. Leonardsen, L., DeClue, J.E., Lybaek, H., Lowy, D.R., and Willumsen, B.M.: Rasp21 sequences opposite the nucleotide binding pocket are required for GRF-mediated nucleotide release. Oncogene 13: 2177-2187, 1996.

  6. Ferrier, A.F., Lee, M., Anderson, W.B., Benvenuto, G., Morrison, D.K., Lowy, D.R., and DeClue, J.E.: Sequential modification of serines 621 and 624 in the Raf-1 carboxy terminus produces alterations in its electrophoretic mobility. J. Biol. Chem. 272: 2136-2142, 1997.

  7. Wienecke, R., Maize, J.C., Reed, J., de Gunzburg, J., Yeung, R.S., and DeClue, J.E.: Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues. Am. J. Path. 150:43-50, 1997.

Last revised on April 14, 1997.

Return to Laboratory of Cellular Oncology