Guo-fu Hu, Ph.D.

The main interest of our lab is how RNA processing is regulated in physiological conditions and how it is dysregulated in cancers and in neurodegenerative diseases. We are focusing on the functions and mechanisms of angiogenin (ANG) and ribonuclease 4 (RNASE4), two members of the pancreatic ribonuclease superfamily, in regulating RNA biogenesis. ANG is universally up-regulated in human cancers and is down-regulated and/or loss-of-function mutated in amyotrophic lateral sclerosis (ALS) and Parkinson's disease. ANG binds to its cell surface receptor plexin-B2 (PLXNB2), is internalized, and translocated to different subcellular compartments to mediate distinct RNA processing events. Under growth conditions and in differentiated cells, ANG is translocated to nucleus where it accumulates in nucleolus to promote ribosomal RNA (rRNA) transcription and stimulate cell growth and proliferation. Under stress conditions and in primitive cell types, ANG is translocated to stress granules and mediates the production of tRNA-derived stress-induced small RNA (tiRNA) that suppresses protein translation and enhances cell survival. We are studying the molecular mechanism of ANG-mediated RNA processing and how this can be harnessed for therapeutic purposes in cancers and in neurodegenerative diseases.