Areas of Interest
Our major focus is the biochemical and molecular dissection of signal transduction pathways under normal physiological conditions and in human disease. Aberrant regulation of signaling pathways is a hallmark of many human diseases, including cancer. In one project in the lab, we are studying the signaling pathways activated by human oncogenes, including K-Ras. In a second project, we are studying signaling pathways that regulate neural regeneration and plasticity, with applications to stroke and Alzheimer’s disease. Our studies are leading to new insights into how signals are transmitted through receptor-mediated pathways to regulate cell growth and differentiation. These studies are also leading to the identification of potential new therapeutic targets for treatment of human diseases.
We employ a variety of biochemical and molecular genetic approaches, such as high throughput screening methods to identify chemical compounds that block specific steps of signaling pathways as well as RNA interference and CRISPR methods to analyze gene function. Our long term objective is a comprehensive and integrated understanding of signaling pathways in human disease with the goal of identifying intervention points for new directions for medical research.
Honors & Awards
2001-2005 American Chemical Society Research Scholar
Vojtek, A. B., Haarer, B., Field, J., Gerst, J., Pollard, T. D., Brown, S., and Wigler, M. (1991). Evidence for a functional link between profilin and CAP in S. cerevisiae. Cell 66, 497-505.
Vojtek, A. B., Hollenberg, S., and Cooper, J. (1993). Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell 74, 205-214.
Fabian, J. R., Vojtek, A. B., Cooper, J. A., and Morrison, D. K. (1994). A single amino acid change in Raf-1 inhibits Ras binding and alters Raf-1 function. Proc. Natl. Acad. Sci. 91, 5982-5986.
Vojtek, A. B. and Cooper, J. A. (1995). Rho family members: Activators of MAP kinase cascades. Cell 82, 527-529.
Graham, S. M., Vojtek, A. B., Huff, S. Y., Cox, A. D., Clark, G. J., Cooper, J. A., and Der, C. J. (1996). TC21 is activated by Ras guanine nucleotide exchange factors but causes transformation by Raf-independent signaling pathways. Mol. Cell Biol. 16, 6132-6140.
Chantry, D., Vojtek, A. B., Kashishian, A., Holtzman, D., Wood, C., Gray, P., Cooper, J. and Hoekstra, M. (1997). p110delta: a novel phosphatidylinositol 3-kinase subunit which associates with p85 and which is expressed predominantly in leukocytes. J. Biol. Chem. 272, 19236-19241.
Winkler, D., Johnson, J., Cooper, J. and Vojtek, A. B. (1997). Identification and characterization of mutations in H-Ras that selectively decrease binding to cRaf. J. Biol. Chem. 272, 24402-9.
Vojtek, A. B. and Der, C. J. (1998). Increasing complexity of the Ras signaling pathway. J. Biol. Chem. 273, 19925-19928.
Guan, K-L., Figueroa, C., Brtva, T., Taylor, J., Barber, T., Zhu, T. and Vojtek, A.B. (2000). Negative Regulation of the B-Raf serine/threonine kinase by Akt. J. Biol. Chem. 275, 27354-59.
Figueroa, C., Taylor, J. and Vojtek, A.B. (2001) PRA1 is a receptor for prenylated small GTPases. J. Biol. Chem. 276, 28219-28225.
Murphy, G. A., Graham, S. M., Morita, S., Reks, S. E., Rogers-Graham, K.,Vojtek, A. B., Kelley, G., and Der, C. J. (2002). Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation. J. Biol. Chem. 277, 9966-9975.
Yu, J-Y., Taylor, J., DeRuiter, S., Vojtek, A. B., and Turner, D.L. (2003). Simultaneous inhibition of GSK3α and GSK3β with hairpin siRNA expression vectors. Molecular Therapy 7, 228-236.
Vojtek, A. B., Taylor, J., DeRuiter, S., Yu, J.-Y. and Turner, D.L. (2003). Akt regulates basic helix-loop-helix/coactivator complex formation and activity during neurogenesis.Molecular and Cellular Biology 23, 4417-27.
Figueroa, C. and Vojtek, A. B. (2003). Akt negatively regulates translation of the ternary complex factor Elk-1. Oncogene 22, 5554-5561.
Figueroa, C., Tarras, S., Taylor, J. and Vojtek, A. B. Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem., in press.
Vojtek, A. B., Taylor, J., DeRuiter, S., Yu, J.-Y. and Turner, D. L. (2003) Akt regulates basic helix-loop-helix/coactivator complex formation and activity during neurogenesis. Molecular and Cellular Biology 23, 4417. PMID: 12808085
Figueroa, C., Tarras, S., Taylor, J. and Vojtek, A. B. (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem. 278, 47922. PMID: 14504284
Chung, K-H., Hart, C. C., Al-Bassam, S., Avery, A., Taylor, J., Patel, P. D., Vojtek, A. B., and Turner, D. L. (2006) Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155. Nucleic Acids Research Apr 13; 3 (7): e53 PMID: 16614444
Avery, A. Figueroa, C. and Vojtek, A. B. (2007) UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3. Cellular Signaling 19, 177. PMID: 16887332
Taylor, J., Chung, K-H., Figueroa, C., Zurawski, J., Dickson, H. M., Brace, EJ., Avery, A. W., Turner, D. L., and Vojtek, A. B. (2008) The scaffold protein POSH regulates axon outgrowth. Mol. Biol. Cell 19, 5181-5192. PMCID: 2592661
Dickson, H. M., Zurawski, J., Zhang, H., Turner, D. L., Vojtek, A. B. (2010) POSH is an intracellular signal transducer for the axon outgrowth inhibitor Nogo66. J. Neuroscience 30, 13319-25. PMID: 20926658