16 Aug Newly Identified Protein Function May Improve Recovery From Radiation for Bone Marrow Transplantation

MedicalResearch.com Interview with:

Dr. Guo-fu Hu

Guo-fu Hu, PhD
Investigator in the Molecular Oncology Research Institute
Tufts Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Angiogenin (ANG) is a ribonuclease that is known to promote cell growth and survival by differential processing of cellular RNAs. This paper reports three main findings.

• 1) ANG has a cell type-specific role in regulating cell proliferation of the hematopoietic system: it promotes quiescence of the primitive hematopoietic stem/progenitor (HSPC) cells while simultaneously stimulating proliferation of more differentiated myeloid progenitor (MyePro) cells.
• 2) ANG regulatesquiescence and proliferation of HSPC and MyePro through a novel mechanism: it induces tRNA-derived stress-induced small RNA (tiRNA) generation in HSPC and ribosomal RNA (rRNA) induction in MyePro, leading to respective reduction and increase in protein synthesis. To our knowledge, this is the first report of cell type specificity in RNA processing that leads to or originates from a different cellular state.
• 3) Recombinant ANG protein is able to improve survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPC in transplantation, which have significant implication in a number of clinical situations including bone marrow failure and stem cell transplantations.

MedicalResearch.com: What should readers take away from your report?

Response: A clinically viable strategy to enhance hematopoietic regeneration for patients undergoing stem cell regeneration and for those who have been or have the risk of being exposed to radiation.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: In order to translate these findings into clinical use and expand the possible scope of clinical applications, we need to:
1) understand the function and mechanism of ANG in regulating other types of cells in the hematopoietic system such as lymphoid progenitor cells,
2) differentiate cell autonomous and non-cell autonomous functions of ANG in regulating hematopoiesis and in enhancing hematopoietic regeneration; and
3) characterize the role of ANG in regulating stem and progenitor cells in other systems.

MedicalResearch.com: Is there anything else you would like to add?

Response: Based on the dichotomous function of ANG in enhancing hematopoietic regeneration, a practical application of recombinant ANG would be to prevent and mitigate radiation exposure in a scenario of catastrophic accident or terrorism. ANG was found to be effective against radiation-induced hematopoietic syndrome and significantly enhanced survival when administered 24 hours either before or after radiation exposure. Currently, there are no FDA-approved drugs to treat severely irradiated individuals. An efficacy requirement was mandated by The Radiation and Nuclear Countermeasures Program at the National Institute of Allergy and Infectious Diseases, and ANG apparently satisfies this requirement. Moreover, current standard-of-care approaches, including (G- Neuprogen (G-CSF) and its derivatives, which is on the list of Strategic National Stockpile, target a limited progenitor cell pool and require repeated doses to combat radiation-induced neutropenia. In this regard, ANG is a promising candidate as a medical countermeasure for radiation exposure.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Angiogenin Promotes Hematopoietic Regeneration by Dichotomously Regulating Quiescence of Stem and Progenitor Cells
Kevin A. Goncalves,Lev Silberstein,Shuping Li,Nicolas Severe,Miaofen G. Hu,Hailing Yang,David T. Scadden ,Guo-fu Hu
CELL Volume 166, Issue 4, p894–906, 11 August 2016

DOI: http://dx.doi.org/10.1016/j.cell.2016.06.042

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Last Updated on August 16, 2016 by Marie Benz MD FAAD