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lab home
The Hu lab
studies angiogenesis in cancers and in neurodegenerative diseases. 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.
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