Our goal is to develop Acomys cahirinus as a new alternative mammalian model system, since they represent the only known mammalian species that retains a remarkable capacity for increased regenerative healing potential across multiple systems as adults. As mammals, the molecular pathways for regenerative repair in Acomys are unique, yet are not likely to be distant from those required for human therapy. Although Acomys may be the best key for unlocking our own capacity for regeneration and untangling the relationship between homeostatic repair versus pathological fibrosis in mammals, Acomys animals for research purposes are more stringently regulated than other rodent models, and hence are currently in limited use in biomedical research. Our innovative approach to enable rapid research across multiple systems has been to first sequence, assemble and annotate a high quality Acomys cahirinus Genomic Resource. Our second step is to develop Acomys Cell and Transgenic Resources to more rapidly facilitate their utilization in biomedical research. Our multipisciplinary Acomys Research Team has extensive evidence that cells from different adult Acomys tissues grow surprisingly well in primary cultures. In fact, isolated Acomys fibroblasts actively resist cytokine-mediated myofiboblast induction by both changing gene expression and by differentially regulating signal transduction kinetics in homeostatic and regenerative pathways. We propose to develop Acomys cell lines from multiple adult tissues, genetically encode them with an array of fluorescent biosensor tools that report activity of key signaling pathways, generating essential tools to unravel the important mechanistic details of Acomys regenerative biology. We also aim to develop transgenic Acomys technology and animals to rapidly facilitate use of these remarkable animals by the broader scientific community. We believe that enabling access and facilitating research into this fascinating experiment of nature offers truly novel possibilities for discovery with far-reaching implications for human regenerative medicine.
New translatable therapies aiming to promote increased regenerative repair and limit chronic fibrosis and inflammatory pathways in humans are urgently required. While most mammals heal wounds and injuries through a fibrotic pathway, rodents from the genus Acomys retain a remarkable capacity for non-fibrotic epimorphic regeneration of skin wounds as adults and we show that aspects of Acomys increased homeostatic regenerative repair properties extend to internal organs and the CNS and into old age. This proposal aims to substantially move forward the broad field of human regenerative medicine by developing Acomys cahirinus as a new mammalian model system with a natural solution for increased regenerative healing for comparative study by developing novel Acomys cell lines genetically encoded with fluorescent biosensors to major signaling pathways and developing transgenic animal capability.
|Adams Waldorf, Kristina M; Nelson, Branden R; Stencel-Baerenwald, Jennifer E et al. (2018) Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nat Med 24:368-374|
|Adams Waldorf, Kristina M; Olson, Erin M; Nelson, Branden R et al. (2018) The Aftermath of Zika: Need for Long-Term Monitoring of Exposed Children. Trends Microbiol 26:729-732|