Research interests
c-Myb is a member of an evolutionarily conserved family of
transcription factors that control the proliferative capacity of cells
during numerous developmental processes. It has been best
characterized for its role during hematopoiesis in controlling early
developmental decisions especially in lymphocyte lineages. Altered
expression or function of the protein is associated with a transformed
state; in fact, the initial Myb family member was identified in an
avian transforming retrovirus.
Much is known about
the regulation of function of the protein and its gene targets;
however, the regulation of expression of the c-myb gene is not
clearly understood. c-myb mRNA levels are highest in early
hematopoietic cells and is down-regulated upon maturation of the
cells. The primary mechanism of down-regulation is through changes in
the elongation proficiency of polymerase complexes in the first intron
of the gene. Studies have shown a role of the NF-kB
family in regulating activation of the gene by binding to Rel-Related
Proteins Binding Elements (RRBE) in the first intron.
Characterization of c-myb expression in this study would be
beneficial in understanding not only regulation of the gene in normal
cells but also regulation in transformed cells. In addition, the
elucidation of the elongation capacity of RNA polymerase II in the
first intron could shed light on general regulatory principles
governing control of gene expression.
The goals of the
project are: (1) determine which NF-kB
family members occupy RRBE sites in c-myb in MEL cells and
murine B cell tumor lines in vivo; (2) characterize occupancy of RRBE
sites by NF-kB
in murine primary B cell substages, and (3) determine the density and
phosphorylation status of RNA polymerase II in the c-myb first
intron in primary murine B cells. The goals will be used to test the
following hypothesis: NF-kB regulates expression of c-myb during murine B cell
lymphogenesis and activation.
Research projects
- Role of c-myb in murine B cell development..
- Identification of factors in yeast that participate in the targeting of proteins for degradation by
antizyme using genetic screens and complementation cloning.
Pre-Graduate School Advising
A new student service has been initiated in the
department to help students who are interested in pursuing
postgraduate education in the sciences. I have set up an
advising program and web site dedicated to informing the PC student
population on how to apply to graduate schools. I hope that
many will take advantage of the resources and faculty to aid in their
pursuit of acceptance into the graduate program of their choice.
Please visit the Pre-Graduate
Advising Program homepage for more information.
Education and training
1983-1987 B.S. (Biology) University of Toledo, Ohio
Research: A study of the self-association of the dinucleotide GpG using NMR and IR spectroscopy.
1987-1993 Ph.D. (Microbiology/Immunology) University of Virginia
Research: A study of the transcriptional regulation of the murine c-myb protooncogene.
1993-1996 Postdoctoral researcher Howard Hughes Medical Institute, University of California, San Francisco
Research: Identification of genes involved in severe combined immunodeficiency disease in humans. Study of the transcriptional activation domain of HIV Tat.
1996-1999 Postdoctoral researcher University of California, San Francisco
Research: Targeting of proteins for degradation via the 26S
proteasome.
Research publications
(undergraduate researchers in bold)
Toth,
C. and Connelly, R. A Bioinformatics experience course. 2006.
Journal of Computing Sciences in Colleges. 21(6):
100-107.
Ingham, R.R., Gesualdi, D.A.,
Toth, C.R. and Clotfelter, E.D.
2004. Effects of genistein on growth and development of aquatic
vertebrates. Bulletin of Environmental Contamination and Toxicology
72: 625-631. PDF
Zavada, M.S., DiMichele, L., and C. Toth.
2004. The demi-lichenization of Tremetes veriscolor II. The
transfer of fixed 14CO2 from the aglal epiphyte to
the fungus. Northeast Naturalist, 11(1):33-40.
Toth, C.R. and Coffino, P. Regulated degradation of yeast ornithine decarboxylase. 1999. Journal of Biological Chemistry. 274:25921-25926.
PDF
Yao, Y., Toth, C.R., Huang, L., Wong, M-L., Dias, P., Burlingame, A.L., Coffino, P., Wang, C.C. Alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings. 1999. Biochemical Journal. 344:349-358.
PDF
Fontes, J.D., Jabrane-Ferrat, N., Toth, C.R., Peterlin, B.M. Binding and cooperative
interactions between two B cell-specific transcriptional coactivators. 1996. Journal of Experimental Medicine. 183:2517-2521.
PDF
Ghosh, S., Toth C.R., Peterlin, B.M., Seto, E. Synergistic activation of transcription by the
mutant and wild-type minimal transcriptional activation domain of VP16. 1996 Journal of Biological Chemistry. 271(17):9911-9918.
PDF
Toth C.R., Hostutler, R.F., Baldwin, A.S. Jr., Bender T.P. 1995. Members of the
NF-kB family transactivate the murine c-myb gene. Journal of Biological Chemistry. 270(13):7661-7671.
PDF
Walmsley, J.A., Schneider, M.L., Farmer P.J., Cave, J.R., Toth C.R., Wilson,
R.M. 1992. Cation-dependence of the self-association behavior of guanylyl-(3'-5')-guanosine. Journal of Biomolecular Structure & Dynamics. 10(3):619-638.
Catron K.M., Toth C.R., Purkerson J., Isakson P., Bender T.P. 1990. Constitutive and cell
cycle regulated expression of c-myb mRNA is related to the state of differentiation in murine B-lymphoid tumors. Current Topics in Microbiology & Immunology . 166:197
Toth C.R., Walmsley J.A. 1988. The preparation and spectroscopic characterization of a weakly
self-associating salt of guanylyl-(3'-5')-guanosine. Biochemical and Biophysical Research Communications 151(1):86.
