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Guo-fu Hu, PhD
Professor of Medicine, Tufts University of Medicine; Principal Investigator, Molecular Oncology Research Institute
Department + Services
Molecular Oncology Research Institute, Guo-fu Hu Laboratory
Our primary interest is the mechanism of action of angiogenin (ANG), a 14kDa angiogenicribonuclease. ANG is up-regulated in various human cancers and is mutated iin some amyotrophic lateral sclerosis (ALS) patients.
A unique feature of ANG, which distinguishes it from the other angiogenic factors, is that it not only triggers signal transduction in endothelial cell, but is also translocated to the nucleus to directly stimulate ribosomal RNA (rRNA) transcription. rRNA are essential components of ribosomes that are crucial for cell growth, maintenance, and survival. Thus, ANG-mediated rRNA transcription is essential for other angiogenic factors to stimulate angiogenesis.
ANG has three types of target cells (endothelial cells, cancer cells, and motor neurons). These cells respond to ANG but exhibit some difference probably due to the difference in ANG receptor expression. Endothelial cells are the first type of responsive cells that have been used extensively for studying ANG biology.
The activity of ANG in endothelial cells is strictly dependent on the cell density in vitro and proliferating status in vivo. ANG receptor is expressed only in sparsely cultured endothelial cells, and in sprouting neovessels in vivo. Cancer cells re the second type of ANG responsive cells. ANG undergoes nuclear translocation in cancer cells in a cell density-independent manner because of the constitutive expression of its receptor. Constitutive nuclear translocation of ANG in cancer cells is a driving force for cancer progression. Motor neurons are the third type of ANG responsive cells.
ANG is strongly expressed in the spinal cord both during development and in the adulthood. Loss-of-function mutations in the coding region of ANG have been found in ALS patients and ANG has been shown to control motor neuron survival. Besides a role in rRNA transcription, ANG also mediates the production of tiRNA, a novel small class of RNA that is derived from tRNA and is induced by stresses. tiRNA reprogram protein translation under stresses to save anabolic energy, enhance damage repairs, and promotes cell survival.
Our research focus is to elucidate the modes of action of ANG in cell growth and survival for the ultimate goal to develop ANG-based therapeutics for cancers and for neurodegenerative diseases.
Email: Guo-fu Hu
Molecular Oncology Research Institute
Tufts Medical Center
800 Washington Street, Box #5609
Boston, MA 02111