Nicholas Polakowski, PhD
Research Associate Professor
BA, New College, Sarasota, FL
PhD, Colorado State University, Fort Collins, CO
Phone: 252-744-3653 or 252-744-2717 (labs), 252-744-2711 (office)
Fax: 252-744-3104
Email: polakowskin@ecu.edu
Research
Disruption of transcription networks serves as the basis for many diseases. This effect is exemplified by the fact that a variety of viral proteins with oncogenic properties participate in different aspects of viral replication and persistence by disrupting host cell transcription. The viral proteins, Tax and HBZ, fall into this category. These proteins are expressed by the complex retrovirus, Human T-cell Leukemia Virus type 1 (HTLV-1), which is the etiologic agent of a fatal malignancy known as Adult T-cell Leukemia (ATL) as well as a number of immuno-inflammatory diseases. Both Tax and HBZ localize to the nucleus and interact with a wide array of cellular transcriptional regulatory proteins to control viral transcription and alter cellular gene expression. Although these effects are essential for HTLV-1 replication and long-term persistence, they also contribute to the development of ATL and other pathological effects caused by the infection. Our research primarily encompasses three focus points. First, we are interested in identifying which cellular genes are transcriptionally deregulated by Tax and HBZ. Second, we are interested in characterizing how these viral proteins alter transcription of their target genes. Third, we are interested in determining whether these alterations in gene expression are involved in the pathogenic events that may arise during the course of infection, such as T-cell transformation, or whether they facilitate other processes associated with infection, such as viral spread and persistence. This information is requisite to the long-term goal of developing a targeted therapeutic approach to treat ATL patients as well as patients with HTLV-1-mediated inflammatory diseases.
Selected Publications
Laverdure S., Polakowski N., Hoang K., Lemasson I. (2016). Permissive sense and antisense transcription from the 5′ and 3′ long terminal repeats of Human T-cell Leukemia Virus type 1. J. Virol. Jan. 20. pii: JVI.02634-15. [Epub ahead of print]
Polakowski N., Terol M., Hoang K., Nash I., Laverdure S., Gazon H., Belrose G., Mesnard J.M., Césaire R., Péloponèse J.M., Lemasson I. (2014). HBZ stimulates brain-derived neurotrophic factor/TrkB autocrine/paracrine signaling to promote survival of human T-cell leukemia virus type 1-Infected T cells. J. Virol. 88(22):13482-94.
Polakowski N., Han H., Lemasson I. (2011). Direct inhibition of RNAse T2 expression by the HTLV-1 viral protein Tax. Viruses. 3(8):1485-500.
Cook P.R., Polakowski N., Lemasson I. (2011). HTLV-1 HBZ protein deregulates interactions between cellular factors and the KIX domain of p300/CBP. J. Mol. Biol. 409(3):384-98.
Polakowski N., Gregory H., Mesnard J.M. and Lemasson I. (2010). Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain. Retrovirology, 7(1):61.
Clerc I., Polakowski N., André-Arpin C., Cook P., Barbeau B., Mesnard J.M. and Lemasson I. (2008). An interaction between the human T cell leukemia virus type 1 basic leucine zipper factor (HBZ) and the KIX domain of p300/CBP contributes to the down-regulation of tax-dependent viral transcription by HBZ. J. Biol. Chem., 283 (35):23903-23913.
Lemasson I., Lewis M., Polakowski N., Hivin P., Cavanagh M.H., Thébault S., Barbeau B., Nyborg J.K. and Mesnard J.M. (2007). HTLV-1 bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription. J. Virol., 81 (4):1543-1553.
Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K. (2006). Tax-dependent displacement of nucleosomes during transcriptional activation of human T-cell leukemia virus, type 1. J. Biol. Chem., 281 (19):13075-13082.
Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K. (2004). Transcription regulatory complexes bind the human T-cell leukemia virus 5’ and 3’ long terminal repeats to control gene expression. Mol. Cell. Biol., 24 (14):6117-6126.
Lemasson I., Polakowski N., Laybourn P.J. and Nyborg J.K.(2002). Transcription factor binding and histone modifications on the integrated proviral promoter in HTLV-I-infected T-cells. J. Biol. Chem., 277 (51): 49459-49465.