The current evidence suggests that the untying of G-quadruplex DNA and RNA structures by helicases such as G4R1 can act as a switch to turn up or turn down gene expression. Research in this field can be applied to a wide range of diseases. Currently the most promising data suggest important roles for G4R1 in human embryonic development, amyotrophic lateral sclerosis (ALS), and AIDS/HIV, and therefore these areas will be the foci for the Smaldino lab. This work is primarily being performed in a human cell culture model.
Other Areas of Research
Dravet Syndrome: A Rare Childhood Epilepsy
Dr. Melissa Smaldino, a co-investigator in the lab, has extensive expertise in neuroscience and epileptic human disorders. There are possibilities in the future for students to work on a project related to these fields. Please inquire for further information.
Gene Silencing in a Yeast Model
We are interested in elucidating the mechanism of an ancient, relatively understudied form of gene silencing, termed tRNA-gene mediated silencing. This mechanism requires the multifunctional protein Mod5, which has the peculiar ability to form prion-like amyloid fibers in yeast. The gene-silencing and amyloid-forming properties are conserved in the human homologue, Trit1, and thus this work has potential implications for human biology and diseases.
Italized author denotes an undergraduate author at the time of the work.
Waller, T.J. , Read, D.F. , Engelke, D.R., Smaldino, P.J. The human tRNA-modifying protein,TRIT1, forms amyloid fibers in vitro. Gene. (Submitted and accepted upon completion of minor revisions- in process)
Read, D.F. , Waller, T.J. , Tse, E., Southworth, D.R., Engelke, D.R., Smaldino, P.J. Direct binding to RNA affects the aggregation and amyloid fiber formation of Mod5. RNA. (Submitted and accepted upon completion of major revisions- in process)
Routh E.D., Beerbower, P.E., Creacy S.D., Akman S.A., Vaughn J.P., Smaldino P.J. G-quadruplex DNA affinity purification of catalytically active G4-Resolvase1. Journal of Visualized Experiments, (Invited submission, abstract accepted, manuscript in preparation)
Carrick B.H. , Hao L., Smaldino P.J., and Engelke D.R. A novel recombinant DNA system for high efficiency affinity purification of proteins in Saccharomyces cerevisiae (2015). Gene Genomes Genetics, 6(3):573-8.
Smaldino P.J., Routh E.D., Kim J.H. , Giri B., Creacy S.D., Hantgan R.R., Akman S.A., Vaughn J.P. (2015) Tight binding of G4 Resolvase1 to telomeric G-quadruplex DNA depends upon the presence of a guanine-containing 3’-tail PLOS ONE. 10(7)
Smaldino P.J., Read D.F. , Pratt-Hyatt M., Hopper A.K., Engelke D.R. (2015) The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer. Gene. 556(1):13-8.
Stoler D.L., Smaldino P.J., Darbary H.K., Sullivan M.A., Rigual N.R., Popat S.R., Hicks W.L., Merzianu M., Gaile D.P., Anderson G.A., Loree T.R. (2013) Human Papillomavirus and Tobacco Usage in Base of Tongue Cancers. Ears, Nose and Throat Ear Nose Throat J. 92(8):372-80.
*Huang W., *Smaldino, P.J., *Zhang Q., Miller L.D., Cao P., Stadelman K., Wan M., Giri B., Lei M., Nagamine Y., Vaughn J.P., Akman S.A., Sui G. (2012) Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1. Nucleic Acids Res. 40(3) 1033-49 *Authors contributed equally
*Giri, B., *Smaldino, P.J., Thys, R.G., Creacy, S.D., Routh, E.D., Hantgan, R.R., Lattmann, S., Nagamine, Y., Akman, S.A., Vaughn, J.P. (2011) G4 Resolvase 1 tightly binds and unwinds unimolecular G4-DNA. Nucleic Acids Res. 39 (16) 7161-78. *Authors contributed equally
Tezal, M., Sullivan Nasca, M., Stoler, D.L., Melendy, T., Hyland, A., Smaldino, P.J., Rigual, N.R., Loree, T.R. (2009). Chronic Periodontitis–Human Papillomavirus Synergy in Base of Tongue Cancers. Archives of Otolaryngology and Head and Neck Surgery, 135(4), 391-6.