Molecular Genetics of Cell Death
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Rheem D. Medh |
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Courses Taught:
Biol 360: General Genetics
Biol 468: Human Genetics
Biol 564: Human Biochemical Genetics
Biol 571: Molecular Diagnostics
Biol 580/L: Cellular Physiology Lecture and Laboratory
Biol 655D: Seminar in Genetics
Research Interests :
My primary interest is in understanding how cells die. There
are multiple forms of cell death; the one I am most interested in is called "apoptosis"
or "programmed cell death". It is a form of cellular suicide, where
the dying cell activates within itself a series of well-orchestrated events including
activation and repression of precise sets of genes, which modulate the execution.
It is becoming increasingly evident that this basic process holds the key to normal
body function, health and disease. Apoptosis has been shown to play a role
in several physiological processes, including development, normal tissue turnover,
immune cell selection, and reproduction. Excessive apoptosis, or a defect in
the process has been implicated in diseases such as neurodegenerative disorders like
Alzheimers, autoimmune disorders, and cancer. My long-term goal is to understand
the biochemical and molecular basis of apoptosis and to utilize this information
to design therapeutic strategies to alleviate or overcome human diseases, particularly
cancer and bone disease.
Currently, I am studying the molecular events associated with apoptosis of leukemic
cells in response to therapeutic agents such as glucocorticoid hormones, immunosuppressants
and anti-proliferative agents, in parallel models of glucocorticoid-sensitive and
resistant human lymphoblastic cells. Using both conventional methods and the
recently developed microarray technology, we have identified a set of genes that
may modulate leukemic cell apoptosis. Each of these genes is being systematically
studied for its role in lymphoid cell apoptosis. This work involves the use
of modern cell and molecular biology techniques such as mammalian cell culture, morphological
and biochemical characterization of cells; DNA and RNA isolation and characterization
by restriction digestion, Southern and Northern blotting and polymerase chain reaction;
protein expression and analysis by Western Blotting; protein-protein interaction
and DNA-protein interaction studies; etc.
There are a number of potential projects for undergraduate and graduate students
interested in this field of research. I encourage students to visit my office
or email me to explore the possibility of pursuing a fulfilling research project
in my laboratory.
Recent Publications:
Hirakawa, Y., Nary, L. J., Orzechowski, P. and Medh, R. D. Glucocorticoid evoked up regulation of MCIP1.1 correlates with apoptosis in human leukemic CEM cells. submitted , Fall 2007.
Priceman, S. J., Kirzner, J. D., Nary, L. J., Morris, D., Shankar, D. B., Sakamoto, K. M., Medh, R. D.. Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells Biochem. Biophys. Res. Commun. 344: 491-499, 2006.
Knockout mouse models for bone studies (as part of the series: Genetically Modified Animals in Endocrinology) Endocrine Reviews, 24: 836-839, 2003 (Compiled by Medh, R.D.)
Medh, R. D., Webb, M. S., Miller, A. L., Johnson, B. H., Fofanov, Y., Li, T., Wood, T. G., Luxon, B. A. and Thompson, E. B. Gene expression profile of human CEM lymphoid cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics, 81: 543-555, 2003
Medh, R.D., Thompson E.B. and Thompson, A.E. Glucocorticoid-induced apoptosis. Encyclopedia of Hormones, Editors-in-Chief: Henry H.L. and Norman A.W., Academic Press, Volume 1: 165-170, 2003.
Medh, R. D. Southern blotting for the analysis of human disease. Encyclopedia of Life Sciences, Nature Publishing Group (www.els.net), 2002.
Medh, R.D. Microarray-Based Expression Profiling of Normal and Malignant Immune Cells (Review) Endocrine Reviews 23: 393-400, 2002.
Miller, A. L., Johnson, B.H., Medh, R. D.,Townsend, C. M., and Thompson, E. B. Glucocorticoids and polyamine inhibitors synergize to kill human leukemic CEM cells. Neoplasia, 4: 68-81, 2002.
Medh, R. D., Wang, A., Zhou, F., and Thompson, E. B. Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells, Oncogene, 20: 4629-4639, 2001.
Medh R. D. and Thompson E. B. Hormonal regulation of physiological cell turnover and apoptosis (Invited Review). Cell and Tissue Research, 301: 101-124, 2000.
Zhou F., Medh, R. D. and Thompson, E. B. The delayed induction of c-jun in apoptotic human leukemic lymphoblasts is primarily transcriptional J. Steroid Biochem. Mol. Biol., 75: 91-99, 2000.
Zhou, F., Medh, R. D. and Thompson, E.B. Glucocorticoid mediated transcriptional repression of c-myc in apoptotic human leukemic CEM cells. J. Steroid Biochem. Mol. Biol., 73: 195-202, 2000.
Johnson, B. H., Russell, M. J., Krylov, A. S., Medh, R. D., Ayala-Torres, S., Regner, J. L. and Thompson, E. B. Structure: apoptotic potency evaluation of novel steroids using human leukemic cells. Lipids, 35: 305-315, 2000.
Thompson, E.B., Medh, R. D., Zhou, F., Ayala-Torres, S., Ansari, N., Zhang, W, and Johnson, B. H. Glucocorticoids, oxysterols, and cAMP with glucocorticoids each cause apoptosis of CEM cells and suppress c-myc. J. Steroid Biochem. Mol. Biol. 69: 453-461, 1999.
Medh R.D., Saeed M.F., Johnson B.H., Thompson E.B. Resistance of human leukemic CEM-C1 cells is overcome by synergism between glucocorticoid and protein kinase A pathways: correlation with c-Myc suppression. Cancer Research. 58(16):3684-93, 1998.
Medh, R.D., Lay, R., and Schmidt, T.J. Agonist-specific modulation of glucocorticoid-mediated transcription by immunosuppressants. Mol. Cell. Endocrinol., 138: 11-23, 1998.
Medh R.D., Schmidt T.J. Trans-retinoic acid and glucocorticoids synergistically induce transcription from the mouse mammary tumor virus promoter in human embryonic kidney cells. J. Steroid Biochem. Mol. Biol., 62(2-3):129-42, 1997
Medh R.D., Santell L., Levin E.G. Stimulation of tissue plasminogen activator production by retinoic acid: synergistic effect on protein kinase C-mediated activation. Blood. 80(4):981-7, 1992