The Role of Protein Synthesis Enzymes in Complex Human Diseases
My research group has been investigating the biology of tRNA and aminoacyl-tRNA synthetases (ARSs) for over two decades. Among discoveries by the PI and the lab are: the first description of minimal tRNA substrates (mini- and microhelix); the characterization of identity elements in the tRNA acceptor stem; the discovery of mechanistic distinctions between class I and class II ARSs, including substrate assisted catalysis; the first characterizations of an aminoacyl-tRNA synthetase-like protein (HisZ) with a function distinct from aminoacylation; fundamental discoveries around ARS editing. In collaboration with investigators from Franklin and Marshall College, we are characterizing a mutant version of human histidyl-tRNA synthetase that is genetically linked to type IIIb Usher Syndrome. Secondly, in a collaborative project with Karen Lounsbury (Department of Pharmacology), we discovered a new function for threonyl-tRNA synthetase in angiogenesis and tumor metastasis. In additional to Dr. Lounsbury, we have recruited a broad team of researchers to investigate this problem, including experts in immunobiology (Matt Poynter, Department of Medicine), zebrafish (Alicia Ebert, Department of Biology), microRNAs (Jane Lian). Through these efforts, we will establish the role of TARS in tumor growth and metastasis, and explore its potential as a molecular biomarker for prostate cancer diagnosis.