Nicholas Wallace, Assistant Professor
412 Ackert Hall
Lab website: http://wallacelabksu.weebly.com
Ph.D. 2008, Tulane University. Biochemistry.
Area(s) of specialization
Human Papillomavirus; Viral Oncogenesis; DNA Damage Repair
Infectious agents cause up to 20% of all human cancers. These oncogenic pathogens include the Human Papillomaviruses (HPVs) that cause cancers of the anogenital and oropharyngeal tracts and may also contribute to the development of non-melanoma skin cancers (NMSC). A cancer caused by these lethal viruses will kill at least 1 woman in the time it takes to read this summary of our work.
HPVs do not encode their own replicative machinery and must hijack polymerases from their host cell. As a result, they are dependent on continually cycling cells for their own replication. To avoid the cell cycle arrest that accompanies DNA damage repair, these viruses express oncoproteins (HPV E6 and E7) that disrupt cell cycle regulation. HPV E6 and E7 accomplish this deregulation both directly by promoting the degradation of cell cycle regulatory proteins and indirectly by attenuating host DNA damage repair. To avoid propagating errors, in response to genomic insults, cells pause their progression through the cell cycle until the lesion is fixed. By diminishing the cell's ability to respond to damage, the virus maintains access to the replicative machinery need for its own life cycle by sacrificing the cell's genomic integrity.
Our lab characterizes the repair deficiencies caused by HPV oncogenes, from two HPV genera with two distinct goals. First, we study the repair deficiencies caused by oncogenes from high risk members of the Alpha Genus (viruses that are the causative agent in cervical and many other cancers), in order to predict novel chemotherapeutic targets for the tumors associated with these viral infections. We are also interested in the Beta genus of HPVs. These viruses are hypothesized to act as a co-factor in non-melanoma skin cancers by inhibiting repair of UV damage. This hypothesis is evaluated in our lab by characterizing the repair of DNA lesions in cells expressing Beta HPV oncogenes.
Wallace, N.A., Robinson, K., Howie, H.L., and Galloway, D.A. 2015. Β-HPV 5 and 8 E6 disrupt homology dependent doubles strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation. PLoS Pathogens, 11 (3).
Wallace, N.A., Robinson, K., and Galloway, D.A. 2014. β human papillomavirus E6 expression inhibits stabilization of p53 and increases tolerance of genomic instability. J Virol., 88 (11).
Wallace, N.A., and Galloway, D.A. 2014. Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin Cancer Biol., 26: 30-42.
Wallace, N.A., Gasior, S.L., Faber, Z.J., Howie, H.L., Deininger, P.L., and Galloway, D.A. 2013. HPV 5 and 8 E6 expression reduces ATM protein levels and attenuates LINE-1 retrotransposition. Virology, 443 (1): 69-79.
Wallace, N.A., Robinson, K., Howie, H.L., and Galloway, D.A. 2012. HPV 5 and 8 E6 abrogate ATR activity resulting in incrased persistence of UVB induced DNA damage. PLoS Pathogens, 8 (7).
Wallace, N.A., Belancio V.P., Faber, Z., and Deininger, P.L. 2010. Feedback inhibition of L1 and alu retrotransposition through altered double strand break repair kinetics. Mob DNA., 1 (1).
View the complete publication list in NCBI