Interdisciplinary Life Science - PULSe Great research is a matter of choice

Vikki Weake

Vikki Weake Profile Picture

Assistant Professor
Ph.D. (Genetics)


Contact Info:

vweake@purdue.edu
765-496-1730


Training Group(s):
Chromatin and Regulation of Gene Expression
Integrative Neuroscience
Computational and Systems Biology


Current Research Interests:

In eukaryotes, such as yeast, flies and humans, our DNA is compacted into a nucleoprotein structure known as chromatin. The histone proteins that wrap around the DNA to form chromatin can be modified by the addition of small chemical and protein molecules, and these modifications are important for regulating both gene expression and genomic integrity. In our lab, we study the SAGA chromatin modifying complex using the fruitfly, Drosophila melanogaster, as a model system. SAGA is a large multi-subunit complex and has two distinct histone modifying activities. It is both a histone acetyltransferase and a histone deubiquitylating enzyme. We are interested in understanding how the different activities of the SAGA complex function mechanistically to regulate transcription and gene expression in specific cell types. Misregulation of SAGA subunits is associated with poor prognosis in specific types of cancer, and we hypothesize that specific activities of SAGA are required in particular cell types for proper regulation of gene expression and cell division.

Why do we think SAGA has tissue-specific functions? Our previous work has identified a role for SAGA in regulating neuronal connectivity in the developing fly eye. Previous studies indicate that SAGA is required in glial cells rather than neurons for proper photoreceptor axon targeting. We are interested in finding out why SAGA is required for axon targeting by identifying genes that are regulated by SAGA in glial cells, and by searching for potential non-histone targets of SAGA in the brain. This work might provide insights into human neurodegenerative disease because a hereditary human neurodegenerative disorder, spinocerebellar ataxia 7, results from mutation of a SAGA subunit also involved in histone deubiquitylation. Furthermore, this ataxia is associated with retinal degeneration and blindness, suggesting that SAGA could also play an important role in eye development and function in humans.



Selected Publications:

 Weake, V. M., & Workman, J. L. (2011). SAGA function in tissue-specific gene expression. Trends Cell Biol., 22, 177-184. Retrieved from http://ac.els-cdn.com/S0962892411002352/1-s2.0-S0962892411002352-main.pdf?_tid=d7321cdd7762818f0b1fd34d8581c1f1&acdnat=1337799317_8ce60e8dea3e969b06e6435642b0b255

Weake, V. M., Dyer, J. O., Seidel, C., Box, A., Swanson, S. K., Peak, A., . . . Workman, J. L. (2011). Post-transcription initiation function of the ubiquitous SAGA complex in tissue-specific gene activation. Genes Dev., 25, 1499-1509. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3143940/pdf/1499.pdf

Weake, V. M., & Workman, J. L. (2010). Inducible gene expression: diverse regulatory mechanisms. Nat. Rev. Genet., 11, 426-437. Retrieved from http://www.nature.com/nrg/journal/v11/n6/pdf/nrg2781.pdf

Schiemann, A. H., Li, F., Weake, V. M., Belikoff, E. J., Klemmer, K. C., Moore, S. A., & Scott, M. J. (2010). Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila. BMC Mol. Biol., 11, 80. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988783/pdf/1471-2199-11-80.pdf

Schiemann, A. H., Weake, V. M., Li, F., Laverty, C., Belikoff, E. J., & Scott, M. J. (2010). The importance of location and orientation of male specific lethal complex binding sites of differing affinities on reporter gene dosage compensation in Drosophila. Biochem. Biophys. Res. Commun., 402, 699-704. Retrieved from http://ac.els-cdn.com/S0006291X10019777/1-s2.0-S0006291X10019777-main.pdf?_tid=a56b584fe3a740cf06709e39df542a9e&acdnat=1337801240_9222a354b8f96044ab7e1805c0b9f169

Weake, V. M., Swanson, S. K., Mushegian, A., Florens, L., Washburn, M. P., Abmayr, S. M., & Workman, J. L. (2009). A novel histone fold domain-containing protein that replaces TAF6 in Drosophila SAGA is required for SAGA-dependent gene expression. Genes Dev., 23, 2818-2823. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800089/pdf/2818.pdf

Weake, V. M., & Workman, J. L. (2009). Hit and run: X marks the spot!. Nat. Struct. Mol. Biol., 16, 801-803. Retrieved from http://www.nature.com/nsmb/journal/v16/n8/pdf/nsmb0809-801.pdf

Weake, V. M., Lee, K. K., Guelman, S., Lin, C. H., Seidel, C., Abmayr, S. M., & Workman, J. L. (2008). SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system. The EMBO J., 27, 394-405. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234343/pdf/7601966a.pdf

Weake, V. M., & Workman, J. L. (2008). Histone ubiquitination: triggering gene activity. Mol. Cell, 29, 653-663. Retrieved from http://ac.els-cdn.com/S1097276508001330/1-s2.0-S1097276508001330-main.pdf?_tid=71b98eda9072bb549db731a7d82553e1&acdnat=1337801878_d7b3f65d2fc146d1f991a9f55c2cd61d

Guelman, S., Suganuma, T., Florens, L., Weake, V. M., Swanson, S. K., Washburn, M. P., . . . Workman, J. L. (2006). The essential gene wda encodes a WD40 repeat subunit of Drosophila SAGA required for histone H3 acetylation. Mol. Cell Biol., 26, 7178-7189. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1592886/pdf/0130-06

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