Program Director/Principal Investigator (Last, First, Middle): Sanchez AlvaradO, Alejandro PROJECT SUIVIMARY (See instructions): The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. This project takes advantage of methodological advances and findings obtained during the last funding period to: 1) define a high temporal resolution, genome-wide, expression profile of regeneration;2) interrogate the functions of known embryonic signaling pathways in the adult contexts of tissue regeneration and homeostasis, and to carry out a formal comparison of how the mechanisms of regeneration compare to embryogenesis;3) uncover genes involved in the regeneration of adult organs after amputation;and 4) Initiate comparative studies of regeneration to test the universality of our findings. All three lines of investigation synergize with each other and their integration should provide us with a high-resolution set of molecular processes regulating regeneration and regenerative capacities. Thus far, this approach has led us to uncover novel animal cell biology and functions in adult contexts of known genes, and to define functions for the many conserved animal genes for which functions are still unknown. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health.

Public Health Relevance

The overarching goal of this project is to define a mechanistic basis for the process of animal regeneration. Given the high degree of evolutionary conservation that exits between planarians and vertebrates, the characterization of gene functions in planarians will advance efforts to study human stem-cell function, regeneration and wound healing, effectively advancing these frontiers of human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37GM057260-16
Application #
8589128
Study Section
Special Emphasis Panel (NSS)
Program Officer
Haynes, Susan R
Project Start
1998-05-01
Project End
2019-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
16
Fiscal Year
2014
Total Cost
$297,000
Indirect Cost
$117,000
Name
Stowers Institute for Medical Research
Department
Type
DUNS #
614653652
City
Kansas City
State
MO
Country
United States
Zip Code
64110
Sánchez Alvarado, Alejandro; Yamanaka, Shinya (2014) Rethinking differentiation: stem cells, regeneration, and plasticity. Cell 157:110-9
Robb, Sofia M C; Sánchez Alvarado, Alejandro (2014) Histone modifications and regeneration in the planarian Schmidtea mediterranea. Curr Top Dev Biol 108:71-93
Rossi, Alessandro; Ross, Eric J; Jack, Antonia et al. (2014) Molecular cloning and characterization of SL3: a stem cell-specific SL RNA from the planarian Schmidtea mediterranea. Gene 533:156-67
Elliott, Sarah A; Sanchez Alvarado, Alejandro (2013) The history and enduring contributions of planarians to the study of animal regeneration. Wiley Interdiscip Rev Dev Biol 2:301-26
Rink, Jochen C; Vu, Hanh Thi-Kim; Sanchez Alvarado, Alejandro (2011) The maintenance and regeneration of the planarian excretory system are regulated by EGFR signaling. Development 138:3769-80
Gurley, Kyle A; Elliott, Sarah A; Simakov, Oleg et al. (2010) Expression of secreted Wnt pathway components reveals unexpected complexity of the planarian amputation response. Dev Biol 347:24-39
Rink, Jochen C; Gurley, Kyle A; Elliott, Sarah A et al. (2009) Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia. Science 326:1406-10