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. 79 available »

2016 Jul
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 Jul; 135(7):707-13. Epub 2016 Apr 07.
2015 Dec
Guy MP, Shaw M, Weiner CL, Hobson L, Stark Z, Rose K, Kalscheuer VM, Gecz J, Phizicky EM. "Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1." Human mutation. 2015 Dec; 36(12):1176-87. Epub 2015 Sep 10.
2015 Sep 28
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 Sep 28; 16:210. Epub 2015 Sep 28.
2015 Sep
Cozen AE, Quartley E, Holmes AD, Hrabeta-Robinson E, Phizicky EM, Lowe TM. "ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments." Nature methods. 2015 Sep; 12(9):879-84. Epub 2015 Aug 03.
2015 Apr
Phizicky EM, Hopper AK. "tRNA processing, modification, and subcellular dynamics: past, present, and future." RNA. 2015 Apr; 21(4):483-5.

Current Appointments

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


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