Philip Smaldino

Philip Smaldino

Assistant Professor of Cell Biology

Phone:765-285-8820

Room:CL 231E


Education and Training

University of Michigan - Postdoctoral Fellowship: 2013-2016
Wake Forest School of Medicine - PhD: 2008-2013
State University of New York at Buffalo - MS: 2006-2008
State University of New York at Fredonia - BS: 2002-2006

Broad Research Interests

Co-investigator: Melissa A. Smaldino, PhD

Basic Science: We are interested in studying “unusual” DNA and RNA structures. We want to know how these structures are modulated by specific enzymes and what effects these interactions have on gene expression.
Application to human disease: This work has significant implications in a diverse field of medical research including embryonic development, HIV/AIDS, and neurodegenerative diseases.

Specific Research Interests

A primary focus of our research is centered around the human enzyme G4R1, which has been shown by us and others to function in a diverse array of cellular processes including transcription, translation, telomere maintenance, embryonic development, and also as a critical sensing molecule needed to activate innate immunity in the presence of certain viral and bacterial DNA and RNA sequences. These functions appear to involve the recognizing and “untying” of DNA and RNA “knots”, known as G-quadruplex (G4) structures. The extent of the effects of this mechanism, and how and where these interactions occur in the cell are largely unknown. These structures are “unusual” in that they are relatively understudied, and there is little mention of these structures in current textbooks, yet there are nearly 1 million of these structures in our genome, representing a massive potential for regulation of cellular processes.

Smaldino graphic

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.

Smaldino graphic

Publications

Underlined 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.