Ales Vancura


Laboratory of Epigenetics

Research Overview
The work in our laboratory is in the area of epigenetics and focuses on the relationship between chromatin structure/transcription and signaling/metabolism. Our long-term goal is to understand how intermediary metabolism affects histone acetylation and transcriptional regulation. Histone acetylation is a dynamic modification that affects chromatin structure and regulates diverse cellular functions, such as gene expression, DNA repair, and cell proliferation. Histone acetylation depends on intermediary metabolism for supplying acetyl-CoA in the nucleocytosolic compartment. Perturbation of the balanced action of histone acetyltransferases (HATs) and histone deacetylases (HDACs) alters the expression pattern of genes involved in cellular growth, resulting in tumorigenesis. Our goal is to identify novel epigenetic targets and strategies for cancer therapy. Our work utilizes yeast and mammalian cell cultures and techniques of molecular and cell biology, biochemistry and genetics.

The work in this Laboratory has been significantly enhanced by the diligent and creative work of our students, who after graduating assumed positions at premier institutions (Rockefeller University, Harvard Medical School, Brown University, New York University, and the National Institutes of Health).

Lab Members
Dr. Luciano Galdieri, Postdoctoral Research Associate
Tiantian Zhang, Ph.D. Student
Daniella Rogerson, Undergraduate Student
Rron Lleshni, Undergraduate Student

1995-1999               American Cancer Society grant BE-239

1997-2000               NIH grant R15 GM55937

2001-2005               American Cancer Society grant RSG-01-145-01-CCG

2006-2009               NIH grant GM076075

2009-2012               NIH grant GM087674

2013-2016               NIH grant GM106324

Mehrotra, S., Galdieri, L., Zhang, T., Pemberton, L.F., Vancura, A. 2014. Histone hypoacetylation-activated genes are repressed by acetyl-CoA- and chromatin-mediated mechanism. Biochim. Biophys. Acta, in press.

Singha, B., Gatla, H.R., Manna, S., Chang, T.-P., Sanacora, S., Poltoratsky, V., Vancura, A., Vancurova, I. 2014. Proteasome inhibition increases recruitment of IkB kinase b (IKKb), S536P-p65, and transcription factor EGR1 to interleukin-8 (IL-8) promoter, resulting in increased IL-8 production in ovarian cancer cells. J. Biol. Chem. 289: 2687-2700.

Galdieri, L., Chang, J., Mehrotra, S., Vancura, A. 2013. Yeast phospholipase C is required for normal acetyl-CoA homeostasis and global histone acetylation. J. Biol. Chem. 288: 27986-27998.

Zhang, M., Galdieri, L., Vancura, A. 2013. The yeast AMPK homolog SNF1 regulates acetyl-CoA homeostasis and histone acetylation. Mol. Cell. Biol. 33: 4701-4717. Selected for Spotlight section of Mol. Cell. Biol.

Galdieri, L., Vancura, A. 2012. Acetyl-CoA carboxylase regulates global histone acetylation. J. Biol. Chem. 287: 23865-23876. Selected as “JBC Best of 2012” and “Faculty 1000 Recommended”.

Vancurova, I., Vancura, A. 2012. NFkB Regulation by Nuclear IkBa in Inflammation and Cancer. American Journal of Clinical and Experimental Immunology 1: 56-66.

Galdieri, L., Desai, P., Vancura, A. 2012. Facilitated assembly of the preinitiation complex by separated tail and head/middle modules of the mediator. J. Mol. Biol.  415: 464-74.

Chang, J., Vancura, A. 2012. Analysis of SUC2 promoter structure by nucleosome scanning. Methods Mol Biol 809: 321-33.

Galdieri, L., Moon, J., Vancura, A. 2012. Determination of histone acetylation status by chromatin immunoprecipitation. Methods Mol. Biol.  809: 255-65.

Galdieri, L., Mehrotra, S., Yu, S., and Vancura, A. 2010. Transcriptional regulation in yeast during diauxic shift and stationary phase. OMICS 14: 629-638.

Guinska, K.,Varghese, R., and Vancura A. 2009. Role of Plc1p in regulation of Mcm1p-dependent genes. FEMS Microbiol. Lett. 295: 245-250.

Desai, P., Guha, N., Galdieri, L., Hadi, S., and Vancura, A. 2009. Plc1p is required for proper chromatin structure and activity of the kinetochore in Saccharomyces cerevisiaeby facilitating recruitment of the RSC complex. Mol. Genet. Genom. 281: 511-523.

Chang, J., Ruiz, V., and Vancura, A. 2008. Purification of yeast memebranes and organelles by sucrose density gradient centrifugation, in Methods in Molecular Biology, vol. 457: Membrane Trafficking (Vancura, A., ed.), Humana Press, Totowa, NJ: pp. 141-149.

Demczuk, A., Guha, N., Nguyen, P.H., Desai, P., Chang, J., Guzinska, K., Rollins, J., Ghosh, C.C., Goodwin, L., and Vancura, A. 2008. Saccharomyces cerevisiaePhospholipase C regulates transcription of Msn2p-dependent stress-responsive genes. Eukaryot. Cell 7: 967-979.

Guha, N., Desai, P., and Vancura, A. 2007. Plc1p is required for SAGA recruitment and derepression of Sko1p-regulated genes. Mol. Biol. Cell 18: 2419-2428.

Romero, C., Dasai, P., DeLillo, N., and Vancura, A. 2006. Expression of FLR1transporter requires phospholipase C and is repressed by mediator. J. Biol. Chem. 281: 5677-5685.

Nguyen, P.H., Hasek, J., Kohlwein, S.D., Romero, C., Choi, J.H., and Vancura, A.2005. Interaction of Pik1p and Sjl proteins in membrane trafficking. FEMS Yeast Res.5: 363-371.

Demczuk, A., Guha, N., Desai, P., Romero, C., and Vancura, A. 2004. Inositol polyphosphates in the yeast nucleus. Recent Res. Devel. Biophys. Biochem. 4: 209-223.

Miskolci, V., Castro-Alcaraz, S., Nguyen, P., Vancura, A., Davidson, D., and Vancurova, I. 2003. Okadaic acid induces sustained activation of NFkB and degradation of nuclear IkBa in human neutrophils. Arch. Biochem. Biophys. 417: 44-52.

DeLillo, N., Romero, C., Lin, H., and Vancura, A. 2003. Genetic evidence for a role of phospholipase C at the budding yeast kinetochore. Mol. Genet. Genom. 269: 261-270.

Lin, H., Nguyen, P., and Vancura, A. 2002. Phospholipase C interacts with Sgd1p and is required for expression of GPD1 gene and osmoresistance in Saccharomyces cerevisiaeMol. Genet. Genom. 267: 313-320.

Lin, H., Choi, J.H., Hasek, J., DeLillo, N., Lou, W., and Vancura, A. 2000. Phospholipase C is involved in kinetochore function in Saccharomyces cerevisiae. Mol. Cell. Biol. 20: 3597-3607.