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
Arnold, Christopher P; Merryman, M Shane; Harris-Arnold, Aleishia et al. (2016) Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38. Elife 5:
Duncan, Elizabeth M; Chitsazan, Alex D; Seidel, Chris W et al. (2015) Set1 and MLL1/2 Target Distinct Sets of Functionally Different Genomic Loci In Vivo. Cell Rep 13:2741-55
Tu, Kimberly C; Cheng, Li-Chun; T K Vu, Hanh et al. (2015) Egr-5 is a post-mitotic regulator of planarian epidermal differentiation. Elife 4:e10501
Thi-Kim Vu, Hanh; Rink, Jochen C; McKinney, Sean A et al. (2015) Stem cells and fluid flow drive cyst formation in an invertebrate excretory organ. Elife 4:
Robb, Sofia M C; Gotting, Kirsten; Ross, Eric et al. (2015) SmedGD 2.0: The Schmidtea mediterranea genome database. Genesis 53:535-46
Adler, Carolyn E; Sánchez Alvarado, Alejandro (2015) Types or States? Cellular Dynamics and Regenerative Potential. Trends Cell Biol 25:687-96
Sánchez Alvarado, Alejandro; Yamanaka, Shinya (2014) Rethinking differentiation: stem cells, regeneration, and plasticity. Cell 157:110-9
Adler, Carolyn E; Seidel, Chris W; McKinney, Sean A et al. (2014) Selective amputation of the pharynx identifies a FoxA-dependent regeneration program in planaria. Elife 3:e02238
Robb, Sofia M C; Sánchez Alvarado, Alejandro (2014) Histone modifications and regeneration in the planarian Schmidtea mediterranea. Curr Top Dev Biol 108:71-93
Xiang, Youbin; Miller, Danny E; Ross, Eric J et al. (2014) Synaptonemal complex extension from clustered telomeres mediates full-length chromosome pairing in Schmidtea mediterranea. Proc Natl Acad Sci U S A 111:E5159-68

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