Investigates the molecular mechanisms underpinning regeneration and scarring in adult tissues using comparative biology approaches that combine mouse repair models with salamander-based tools for discovery.
Finding regenerative strategies capable of faithfully repairing tissues after surgery, disease or traumatic injury will have the potential to transform modern medicine and improve the lives of a limitless number of patients.
In dramatic contrast to the poor repair outcomes for humans and rodent models such as mice, salamanders are able to completely regenerate heart tissue, whole limbs and many other tissues following injury, at any life stage. This astounding capacity for repair provides a template on which to understand the process of natural regeneration and develop strategies to improve human repair.
Dr Godwin’s work explores the molecular signals from nerve and immune cells that underpin the resistance to scarring, and the activation of regeneration in salamanders. This work combines both comparative biology and immunomodulation to investigate the potential for regeneration in a range of genetic mouse models.
Dr Godwin holds a dual appointment at the Jackson Laboratory and MDI Biological laboratory.
Human clinical trials in type 1 diabetes (T1D) patients using mesenchymal stem cells (MSC) are presently underway without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in NOD mice. In comparison to NOD mice, BALB/c-MSC mice were found to express higher levels of the negative costimulatory molecule PD-L1 and to promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e., nonobese resistant mice or BALB/c), but not from NOD mice, delayed the onset of diabetes when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c-MSC temporarily resulted in reversal of hyperglycemia in 90% of NOD mice (p = 0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit. We also noted soft tissue and visceral tumors in NOD-MSC-treated mice, which were uniquely observed in this setting (i.e., no tumors were present with BALB/c- or nonobese resistant mice-MSC transfer). The importance of this observation remains to be explored in humans, as inbred mice such as NOD may be more susceptible to tumor formation. These data provide important preclinical data supporting the basis for further development of allogeneic MSC-based therapies for T1D and, potentially, for other autoimmune disorders.
Recently, a team led by JAX Professor and Scientific Director Nadia Rosenthal, Ph.D., F.Med.Sci., and Research Scientist James Godwin, Ph.D., explored the role of the immune response in heart regeneration in the axolotl (salamander).