Jessica Whited studies limb regeneration in axolotl salamanders, with the ultimate goal of discovering how to regenerate limbs in patients.

The Whited lab develops tools to manipulate gene expression during limb regeneration, and explores signaling events following wound healing that initiate the regenerative process.

Humans and other mammals have extremely limited regenerative capabilities in key parts such as limbs.  Nearly two million Americans are currently living with the consequences of having undergone limb amputation due to injury or disease, and this number is expected to rise. No biological therapeutic has been devised to address this problem.

In contrast, axolotl salamanders can replace entire lost limbs throughout life, and these limbs are anatomically similar to human limbs. This amazing feat presents an opportunity to learn about natural cellular reprogramming in animals. While axolotl limb regeneration has been known for centuries, much of the crucial mechanistic detail at the molecular level has remained elusive.

We have developed powerful tools to investigate limb regeneration in axolotls with the hope that understanding how limb regeneration occurs in these animals will provide information critical for designing efforts to stimulate regeneration in humans. A crucial question is how the animals use the blastema, a collection of relatively dedifferentiated cells and stem cells derived from stump tissues, to orchestrate the regeneration of an entire limb. Mammals do not respond to most amputations by creating blastemas, and this difference may underlie their inability to regenerate. In the Whited lab, we aim to understand the molecular mechanisms at work in the axolotl blastema so that we can later understand why mammals cannot regenerate limbs.

The Whited lab is taking several approaches aimed at understanding how blastemas facilitate regeneration. One key question is how blastema cells keep from differentiating. A second key question is how blastema cells keep track of what tissues beget them, and what types of daughter cells they can produce. We are also interested in identifying the tissues that support the essential elements of blastema cells such as their formation and proliferation.

To examine these questions, we are using retroviral infections, transgenesis, and knock-down approaches to analyze the function of genes we have identified in sequencing efforts. We hope that this work will lead to an improved understanding of the basic biology at work in blastemas in these highly-regenerative organisms, providing a framework to approach the roles of these factors in organisms with more restricted natural regenerative abilities. 

Biosketch

Jessica Whited is an Assistant Professor of Stem Cell and Regenerative Biology at Harvard University. She earned a B.A. in Philosophy and a B.S. in Biological Sciences from the University of Missouri, and obtained her Ph.D. in Biology from MIT, where she studied in Dr. Paul Garrity’s laboratory. Whited's thesis focused on molecular mechanisms controlling the development and maintenance of cellular architectures in the Drosophila nervous system. During this work, Dr. Whited became interested in processes that may be required long after initial developmental events to ensure cells do not revert to immature behaviors, as well as processes that provoke such events in response to injury. She worked in the laboratory of Dr. Cliff Tabin (Harvard Medical School Department of Genetics) as a postdoc studying total limb regeneration in axolotl salamanders. During this time, Whited developed several molecular tools that can be used to interrogate regenerating axolotl limbs.