The central tenet of regenerative medicine is to unlock the genetic programs that promote natural tissue regeneration. However, a major roadblock to achieving this reality is our lack of understanding of the genetic mechanisms that underscore complex tissue regeneration. Appendages -limbs, tail, and fins -are the most studied model organs in non-mammalian regeneration research based on the accessibility of the organs, as well as the efficiency and near perfection of restoration of a three-dimensional tissue comprised of many cell types. While appendage regeneration in mammals is restricted to the distal tips of digits, the zebrafish has maintained an enhanced capacity to regenerate multiple appendage tissues, including bone, nerves, blood vessels, epidermis and pigment cells. Our research program exploits the experimental and genetic prowess of the zebrafish to address two fundamental questions that underscore appendage regeneration. What molecular pathways regulate the natural cellular reprogramming from differentiated, quiescent tissues into highly proliferative, regenerative cells in response to injury? Is there is a core regulatory cascade that defines regenerative outgrowth and patterning during tissue replacement. Specifically, we will test the hypothesis that microRNAs play key roles in the initiation and maintenance of proliferative progenitor tissue during appendage regeneration. Understanding which specific molecular programs by which nonmammalian vertebrate model systems faithfully regrow complex organs will provide the basis for potential regenerative therapies.
Our studies are significant and innovative because we will elucidate the genetic foundation that drives natural cellular reprogramming and tissue replacement during appendage regeneration. These studies will enhance potential therapies to aid wound healing and repair in humans and provide perspective for changing the existing limitations in regenerative capacity of most human organs.
|Lisse, Thomas S; Rieger, Sandra (2017) IKK? regulates human keratinocyte migration through surveillance of the redox environment. J Cell Sci 130:975-988|
|Duong, Michelle; Yu, Xuejiao; Teng, Beina et al. (2017) Protein kinase C ? stabilizes ?-catenin and regulates its subcellular localization in podocytes. J Biol Chem 292:12100-12110|
|Andralojc, Karolina M; Campbell, Anne C; Kelly, Ashley L et al. (2017) ELLI-1, a novel germline protein, modulates RNAi activity and P-granule accumulation in Caenorhabditis elegans. PLoS Genet 13:e1006611|
|King, Benjamin L; Yin, Viravuth P (2017) Prioritizing studies on regeneration in nontraditional model organisms. Regen Med 12:1-3|
|Godwin, James W; Pinto, Alexander R; Rosenthal, Nadia A (2017) Chasing the recipe for a pro-regenerative immune system. Semin Cell Dev Biol 61:71-79|
|Rochester, Jesse D; Tanner, Paige C; Sharp, Catherine S et al. (2017) PQN-75 is expressed in the pharyngeal gland cells of Caenorhabditiselegans and is dispensable for germline development. Biol Open 6:1355-1363|
|Reid, Noah M; Jackson, Craig E; Gilbert, Don et al. (2017) The landscape of extreme genomic variation in the highly adaptable Atlantic killifish. Genome Biol Evol :|
|Zhu, Shusen; Coffman, James A (2017) Simple and fast quantification of DNA damage by real-time PCR, and its application to nuclear and mitochondrial DNA from multiple tissues of aging zebrafish. BMC Res Notes 10:269|
|Davis, Allan Peter; Grondin, Cynthia J; Johnson, Robin J et al. (2017) The Comparative Toxicogenomics Database: update 2017. Nucleic Acids Res 45:D972-D978|
|Smith, Ashley M; Maguire-Nguyen, Katie K; Rando, Thomas A et al. (2017) The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues. NPJ Regen Med 2:4|
Showing the most recent 10 out of 52 publications