Iswar Hariharan

American Cancer Society Research Professor
Professor of Cell and Developmental Biology
Department of Molecular and Cell Biology
University of California, Berkeley

Many adult human organs are incapable of repairing tissue that has been damaged as a result of injury or disease. When sufficient tissue damage occurs, the function of organs can be compromised, sometimes severely, resulting in significant morbidity and mortality. Improving the regenerative capacity of adult tissues would dramatically impact the clinical management of these and related medical conditions.
Most adult animals have a limited capacity for regenerating structures that are damaged as a result of disease or injury. Remarkably, some animals (e.g. planaria, salamanders) retain the ability to regenerate many of their adult organs. We currently have little understanding of why certain organisms and organs can regenerate while others cannot.

Currently, research on regeneration is hampered by the inability to study regenerative growth in genetically tractable model organisms. Genetic studies in Drosophila, including those conducted in our laboratory, have contributed significantly to our understanding of the pathways that regulate growth during normal development. However, screens for genes that regulate regeneration have, so far, not been possible. Classical experiments using surgical ablation and transplantation have shown that Drosophila imaginal discs, the precursors of adult structures such as the wing and eye, have extensive regenerative capacity. However, those approaches were extremely labor-intensive and are not easily incorporated into genetic screens.

Hence, we have developed a genetic method of inducing ablation and regeneration in imaginal discs that is not dependent on surgical manipulations. This allows us to take advantage of all the tools of Drosophila genetics, as well as reagents developed to study growth regulation in Drosophila, to address key questions that pertain to regenerative growth. These include: (1) How does regenerative growth differ from normal growth (2) What determines whether a tissue is capable of regeneration? (3) Why does regenerative growth stop when normal organ size is restored? (4) How does tissue regeneration affect the rest of the organism? We anticipate that these studies will help us understand how regenerative growth and regenerative capacity are regulated and eventually lead to the design of strategies for promoting regeneration in damaged human tissues.