Mark Danielsen, PhD
Department of Biochemistry
Basic Science Building, Rm 355
3900 Reservoir Road, NW
Washington, DC 20057-1455
Phone: 202 687-4169
Fax: 202 687-7186
Steroid receptors, Bioterrorism, Bioinformatics, Endocrine Distrupors
My research interests include the interaction of the androgen receptor (AR) with regulators of the cell cycle, alteration of the AR signal cascade due to environmental hormone disrupters, changes in gene expression in Li-Fraumeni syndrome (partial p53 deficiency), and development of novel mechanisms to detect biological threat organisms such as anthrax and smallpox.
AR and the cell cycle. We have shown that pRB acts as a coactivator of the AR and that E2F inhibits the AR. Our collaborator, Karen Knudsen, has shown that cyclin D1 inhibits the AR. As might be expected from these data, AR activity varies during the cell cycle. We are testing the hypothesis that control of AR activity during the cell cycle is integral to the various functions of the AR, namely cell growth, differentiation and prevention of apoptosis.
AR and hormone disruptors. In collaboration with Mary Beth Martin, we found that cadmium activates the AR and stimulates growth of human prostate cancer cells. In a related project, in collaboration with Carlos Suarez, we found that methoxyacetic acid (MAA), a metabolite of an industrial solvent found in paint thinners, can stimulate the transcriptional activity of the AR in cells and that MAA alters the developmental expression of androgen responsive genes during spermatogenesis and leads to decreased fertility. Our goal is to map changes in hormone pathways during development due to the action of endocrine disruptors both in utero and in later life.
P53. We are exploring the role of a novel gene that is differentially expressed in patients with Li-Fraumeni syndrome (p53 deficiency). We know that it is differentially expressed in a number of tissues. We are determining its function using a mixture of bioinformatics, overexpression and mutation techniques.
Identification of Biological threat agents
This project is a collaboration between Georgetown University, Antion Corporation, Molecular Staging Inc and Lawrence Livermore National Lab. We have developed novel technologies for the identification of biological threat agents: a stand-alone device is in development.
- Danielsen, M. (2001) Bioinformatics of Nuclear Receptors. Meth. Mol. Biol. 176: 3-22.
- Zhang, S., Lu, J., Iyama, K, Lo, S.C., and Danielsen M. (2001) A simplified method for large scale quantification of transcriptional activity and its use in studies of steroids and steroid receptors. J. of Receptor and Signal Transduction Research 21, 71-84.
- Martn, M.B., Voeller, H.J., Gelmann, E.P., Lu, J., Stoica, E.-G., Danielsen, M., Pentecost, E., Stoica, A. (2002) A. Role of cadmium in the regulation of androgen receptor gene expression and activity. Endocrinology 143(1): 263-275.
- Petre, CE, Wetherill, YB, Danielsen, M, Knudsen, KE. (2002) Cyclin D1: mechanism and consequence of androgen receptor co-repressor activity. J Biol Chem 277: 2207-2215.
- Martinez, E. and Danielsen, M. (2002) Loss of androgen receptor transcriptional activity at the G1/S transition. J. Biol. Chem. 277: 29719-29729.
- Tirado, O.M., Martinez, E.D., Rodriguez, O.C., Danielsen, M., Selva, D.M., Reventos. J., Munell, F., and Suarez-Quian, C.A. (2003) Methoxyacetic acid disregulation of androgen receptor and androgen-binding protein expression in adult rat testis. Biology of Reproduction 68:1437-1446.