Eric M. Phizicky, Ph.D.

Eric M. Phizicky, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 275-7268
Fax: (585) 271-2683

Research Bio

tRNA Biogenesis, Function and Quality Control

One major lab project focuses on understanding the biology of tRNA. tRNA plays a crucial role in translation, and numerous factors participate in its biogenesis, function, intracellular trafficking, and quality control. In the yeast Saccharomyces cerevisiae, cytoplasmic tRNAs have an average of 13 modifications, and there are a total of 25 chemically distinct modifications, many of which are highly conserved in different organisms, and of unknown function. We previously used a biochemical genomics approach to identify the genes encoding a number of different modification enzymes. We are currently focusing on the assignment of other activities to genes, and on two aspects of the biology of modifications: First, we are investigating the roles of modifications. We recently found evidence that lack of certain modifications can lead to rapid degradation of specific mature tRNAs, suggesting the existence of a quality control pathway that monitors the integrity of tRNA. We are currently working to define the components of this rapid tRNA decay pathway, the mechanism by which tRNAs are targeted for turnover, and the conditions under which this pathway is used. Second, we are defining the mechanisms by which modification enzymes recognize and act on their specific tRNA substrates. Since modifications have crucial roles in the cell, incorrect modification of a tRNA is likely to have catastrophic effects. We recently found that recognition of the tRNAHis anticodon is necessary and sufficient for Thg1 to add a guanine nucleotide to the 5' end of the tRNA, a reaction that is essential in wild type cells for proper translation. We are currently examining other modification enzymes to uncover the different mechanisms by which specificity is attained.

Functional Genomics

A second major lab project focuses on the design, construction and implementation of genomic methods to analyze protein structure and function (in collaboration with Elizabeth Grayhack). To facilitate parallel biochemical analysis of the proteome, we previously constructed two genomic libraries of strains in which nearly every yeast gene is expressed as a tagged fusion protein under regulated control. We are currently using these libraries to define new biochemical activities, and to help define cell circuitry by systematic analysis of genetic suppression caused by overexpression of genes. In addition, in collaboration with investigators at the Hauptman-Woodward Institute, we are developing methodology for high throughput expression and purification of protein complexes from yeast, for structural analysis by x-ray crystallography.

Recent Journal Articles

Showing the 5 most recent journal articles. 76 available »

2016 Apr 7
Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, Phizicky EM, Alkuraya FS. "A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition." Human genetics. 2016 Apr 7; Epub 2016 Apr 07.
2015 Feb
Han L, Kon Y, Phizicky EM. "Functional importance of ?38 and ?39 in distinct tRNAs, amplified for tRNAGln(UUG) by unexpected temperature sensitivity of the s2U modification in yeast." RNA. 2015 Feb; 21(2):188-201. Epub 2014 Dec 12.
2015 Jan
Guy MP, Phizicky EM. "Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes." RNA. 2015 Jan; 21(1):61-74. Epub 2014 Nov 17.
Payea MJ, Guy MP, Phizicky EM. "Methodology for the High-Throughput Identification and Characterization of tRNA Variants That Are Substrates for a tRNA Decay Pathway." Methods in enzymology. 2015 560:1-17. Epub 2015 Apr 27.
Shaheen R, Abdel-Salam GM, Guy MP, Alomar R, Abdel-Hamid MS, Afifi HH, Ismail SI, Emam BA, Phizicky EM, Alkuraya FS. "Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism." Genome biology. 2015 16:210. Epub 2015 Sep 28.

Current Appointments

Dean's Professorship - Department of Biochemistry and Biophysics (SMD)
Professor - Department of Biochemistry and Biophysics (SMD) - Primary
Professor - Cancer Center
Professor - Department of Pediatrics (SMD)


PhD | Biochemistry | Cornell University1983
BS | Biochemistry | McGill University1976