Guo-Fu Hu, PhD
Assistant Professor
Department of Pathology, Harvard Medical School
Angiogenin and its role in disease: angiogenesis, cancer, neurodegenerative diseases
Investigate angiogenin’s mechanism of action and its role in cancer and neurodegenerative disease, with a focus on prostate cancer and ALS.
Commercial Opportunities
Investigate angiogenin's role in disease processes such as cancer and ALS, with the goal of developing novel therapeutics
The compelling data linking angiogenin activity following nuclear translocation to stimulation of endothelial growth, angiogenesis, and cancer cell proliferation have significant therapeutic implications. This link is clearly demonstrated by the published experiments on neomycin and neamine that halt angiogenin’s migration to the nucleus and concomitantly block tumor growth. Thus, several molecular targets in the angiogenic pathway may be amenable for drug development, including angiogenin itself (particularly because it is a secreted protein), the angiogenin receptor, the nuclear translocation of angiogenin, the binding of angiogenin to DNA, and its ribonuclease activity.
The new revelations about the potential role of angiogenin in ALS could open up an entirely new avenue of drug discovery for therapeutic intervention, particularly because angiogenin is the first gene in which loss-of-function mutations have been linked to ALS
Current Research Interests
Determine if angiogenin confers a protective function for neurons, and if loss-of-function angiogenin mutations are sufficient to trigger the onset of ALS.
Investigate the activity of ODC antizyme in DNA repair and tumor suppression.
Study the possible intersection of angiogenin and growth factors in stimulating angiogenesis and cancer progression.
Further dissect angiogenin’s nuclear localization as a target for drug therapy.
Investigate the in vivo consequences of angiogenin loss-of-function mutations and their role in neurodegenerative diseases, for the purpose of developing more authentic mouse models of diseases, such as ALS. The current “gold” standard for an ALS mouse model involves superoxide dismutase gain-of-function mutations, but experimental therapies that appear effective in this mouse model have not demonstrated efficacy in humans.
Study the tumor suppressor function of ODC antizyme in mouse models to gain insights into its mechanism of action.
Research Expertise
Dr. Hu’s laboratory has been studying the biological function of angiogenin, a 14 kDa secreted ribonuclease, for many years. This research has uncovered several features of angiogenin biology, including: nuclear translocation in cancer cells, DNA binding to the rRNA promoter, a potent angiogenesis-stimulating activity, and promotion of cancer cell proliferation. The lab’s studies, linking angiogenin to tumor growth, have been the subject of several high-profile articles, that demonstrated the following:
1. Angiogenin directly promotes cancer cell growth.
2. Translocation of angiogenin to the nucleus and its ability to stimulate rRNA transcription correlate with cancer cell growth.
3. Blockage of angiogenin translocation to the nucleus by the antibiotic neomycin or its nontoxic derivative neamine, or curbing of angiogenin expression by RNA interference, leads to a repression of tumor cell growth.
4. Angiogenin plays an important role in endothelial cell growth and angiogenesis.
The data are particularly compelling with respect to prostate cancer, which displays significantly elevated angiogenin expression relative to normal prostate tissue.
Recent work has also revealed an intriguing link between angiogenin and the debilitating and fatal neurodegenerative disease ALS.