PI Stephen Badylak, DVM, PhD, MD
Co-PIs
- Susan Braunhut, Ph.D., professor of biological sciences at the University of Massachusetts at Lowell
- Lorraine Gudas, Ph.D., chairman of the pharmacology department and Revlon Pharmaceutical Professor of Pharmacology and Toxicology, Weill Medical College of Cornell University, New York City
- Ellen Heber-Katz, Ph.D., professor, molecular and cellular oncogenesis program, The Wistar Institute in Philadelphia
Shannon Odelberg, Ph.D., assistant professor, departments of internal medicine and neurobiology and anatomy, University of Utah, Salt Lake City - Hans-Georg Simon, Ph.D., a developmental biologist and assistant professor of pediatrics, Children’s Memorial Research Center and Northwestern University in Chicago
Title Mammalian Limb Restoration
Summary The regenerative ability of adult human tissues, organs, and appendages is typically very limited. The default mechanism of wound repair in humans and most other mammals is characterized by scar tissue formation. However, there is evidence for some site-specific regeneration-like processes during mammalian embryologic development and during the early postnatal period. In addition, there is lifelong self-renewal capability for selected cell populations such as hematopoietic cells, intestinal epithelium, and hepatocytes.
In contrast, urodele amphibians possess extraordinary abilities to regenerate lost structures, such as the limbs and tail, throughout their lifetime. These regenerative processes are dependent upon the formation of a blastema at the site of injury. This regeneration blastema is comprised of a self-organizing pool of proliferating progenitor cells genetically programmed to develop into a phenocopy of the lost structure.
The blastema carries its own extracellular matrix and its own gene expression signature. The work described in this project will attempt to unlock the regenerative potential in humans by determining the genetic signature of the developing blastema and attempting to recreate portions of the fetal development process in humans.
The research will involve several milestones including identification of cells that participate in the formation of a blastema-like structure in mammals, the spatiotemporal location of such cells during the remodeling process and the identification of bioactive molecules that induce, maintain, and complete such a process.
The culmination of this work would eventually be the application of these identified mechanisms and events to the injured mammal in a mouse model.
A highly interdisciplinary research team has been developed with expertise in developmental biology, molecular biology, matrix biology, pharmacology, immunology, and with training in medicine, veterinary medicine, physics, and computational methods of data mining. Significant preliminary data has been generated to support the fundamental approach. Well defined milestones have been identified and a management scheme has been established that assures close collaboration among the principal investigators and their respective laboratories at six different institutions.
Source DARPA (W911NF-06-1-0067)
Term 1 year with provisions for extensions