Using comparative biology to decipher regeneration codes and develop novel drug therapies for regenerative medicine
The U.S. department of Health and Human Services has called regenerative medicine the “vanguard of 21st-century healthcare.” Regenerative medicine focuses on replacing, engineering or regenerating human cells, tissues and organs that have been damaged by disease, injury and aging. Much of the field to date has concentrated on development of stem cell-, gene- and tissue-engineering-based therapies. Despite extensive research, these potential therapeutic strategies are challenged by their complexity and high cost and by significant efficacy and regulatory hurdles.
Discovery and development of small molecules capable of activating innate tissue repair and regenerative processes is a newly emerging field in regenerative medicine. Small molecules have multiple advantages compared to other regenerative medicine therapeutic strategies including greatly reduced complexity, reduced regulatory hurdles, ready reversibility and lack of ethical concerns that have challenged the stem cell field. Small molecule therapies will also likely cost less to administer compared to cell-, gene- and tissue engineering-based approaches and will thus be accessible to a much greater number of patients suffering from debilitating diseases and injuries.
Despite its enormous potential, progress in regenerative medicine drug development is currently constrained by our limited understanding of how regeneration is controlled in organisms with robust regenerative capabilities, and of why most human tissue and organ systems have limited or no regenerative capacity. Put very simply, the specific mechanisms and proteins that can be targeted with drugs to activate innate tissue repair and regenerative processes in patients are largely unknown.
Regeneration, like development, is a predictable biological process. The source of this predictability is the regulatory information encoded in gene and signaling networks. Using genomic methods and comparative analyses of judiciously chosen animal models and experimental systems, it is possible to readily identify gene networks and signaling pathways underlying regeneration. These networks and pathways can then be experimentally validated and refined in an iterative approach similar to that which has been applied successfully to decipher the gene regulatory networks that control embryonic development.
The Center of Biomedical Research Excellence at the MDI Biological Laboratory is uniquely focused on defining the gene and signaling networks that control regeneration and aging, on using the regulatory information encoded in those networks to identify potential drug targets, and on assessing the therapeutic value of targets through small molecule screens and early preclinical development efforts. Our approach is founded on the extensive expertise of our scientists in regenerative and aging biology, diverse animal models, genomics, bioinformatics, integrative physiology, comparative and evolutionary biology and drug discovery. Current research efforts in the Center focus on defining the gene regulatory networks and signaling pathways underlying heart, nerve and limb regeneration, wound healing, immune responses to injury, stem cell function and the loss of regenerative capacity with stress and age, and on preclinical development of lead drug candidates.