Jessica Whited, PhD, has fond memories of exploring the outdoors when she was younger—catching crayfish with her sister and studying butterflies and moths with her mother. Now a researcher at the BWH Regenerative Medicine Center, Whited devotes her days to understanding limb regeneration in a certain species of salamanders and how research on these creatures could one day help humans suffering from limb loss.
BWH Clinical & Research News recently sat down with Whited to discuss the events that have shaped her career path and research interests.
Tell us about your work. How could your research help patients one day?
JW: My work is devoted to understanding limb regeneration in axolotl (Mexican) salamanders. The salamanders I study have legs that look and function very much like human limbs. They have a similar shape and pattern to their bones and can completely regenerate these limbs, even as adults. If we understood how this worked, the information would be very helpful for designing strategies to try to awaken this response in human limbs. Limb loss is a major health concern, and millions of Americans are currently living with the consequences of having a major limb amputation. Some of these consequences are due to injuries, and an equal—and rising—number are due to diseases, including diabetes and peripheral artery disease.
While other researchers are taking different approaches, some of which may be complementary, I believe that if we want limb regeneration in humans to become reality, we’ll only get there if we first understand how nature has solved this problem. That’s why we’re studying salamanders.
How did you get interested in your field?
JW: I was born in Monroe, Mich., a small town situated between Detroit and Toledo, Ohio. My father built cars on the assembly line for General Motors. My mother was a stay-at-home mom, but she was also something of an amateur lepidopterist—a person interested in butterflies and moths. She taught me how to identify, catch and display butterflies, and I remember making my big score of a perfect tiger swallowtail on the ashes of our previous night’s campfire at the age of five. I really attribute my love of nature, which eventually gave rise to my interest in science, to these early experiences outdoors.
When I was eight, my father was transferred to a new assembly plant in Missouri. We moved into a house very close to a creek. I vividly remember my sister and I going to the creek to catch crayfish with our hands and coffee cans.
My grandfather was afflicted with peripheral artery disease. He underwent a series of amputations starting with a few toes and culminating in his foot before he eventually died of the condition at 62. I was in college at the time. I saw him in the hospital with gangrenous toes. This was my first encounter with this disease. I hope that someday our work will help people with this condition.
Take us through your career path. Where did you study and have you worked anywhere else?
JW: As an undergraduate, I attended the University of Missouri (Mizzou) on a full academic scholarship, at the College of Agriculture, Food & Natural Resources. My first lab job was in a soil science lab. After some time there, I began running some of the routine analyses, and had the opportunity to dig through samples and identify species of earthworms inside. In the meantime, I tutored students in chemistry and biology. That’s when I discovered I really love teaching.
Following undergraduate studies, I was fortunate to work for two brilliant professors. In graduate school at MIT, I worked in the lab of Biology professor Paul Garrity, PhD, where we used fruit flies to study neuronal development. As a postdoc at HMS Genetics, I worked in the lab of Cliff Tabin, PhD. Cliff had worked on salamander limb regeneration a couple decades earlier, and he was psyched that I wanted to re-initiate some of these kinds of studies in his lab.
Tell us more about what it’s like working with salamanders
JW: Working with axolotls is a ton of fun and also a lot of work. They are permanently aquatic, which means we devote a great deal of time to keeping them clean and their water in good shape. I have a technician from the New England Aquarium who has implemented some awesome ideas for getting the facility more efficient. We have hundreds of axolotls at all life stages.
Many species of salamanders can regenerate limbs. We work on axolotls specifically, though, because they have a relatively short generation time. That means the time it takes for them to be born to when they can have babies is shorter than many other salamanders. For axolotls, this time is nine months.
Why did you decide to focus on limb regeneration?
JW: I wanted to work on something that was in an introductory biology textbook as a phenomenon, but for which we didn’t have any real clue how the nuts and bolts worked. There were other topics that were also interesting to me at the time, for instance, bird song. When you pick a topic for your postdoc, you have to be careful because you’ll be expected to start your lab studying that general topic. I also considered how much was left to be discovered in the field, how relevant the findings might be to human health and whether I thought the topic would get me out of bed in the morning. You also want to pick something that youngsters find fascinating because you have to populate your lab with students.
People have known that salamanders can regenerate limbs for a few hundred years, and a ton of interesting, and sometimes perplexing experiments, have been conducted to figure out why. I loved reading these old manuscripts and then imagining how we might take these hints and figure out the molecules now that we have better tools.
What types of genetic tools are you working on developing?
JW: Right now we are developing a couple of tools. In collaboration with the Broad Institute of MIT and Harvard, we are making a map of all the genes that get turned on or off during regeneration and which are special to the regenerating part of the leg. We’re also mapping how this changes over time and with respect to specific kinds of cells. One of the most powerful ways of figuring out what a gene does is to get rid of it and see what happens, in this case see what happens to regeneration. Because some genes are required for other processes, we’d like to be able to remove genes just in the regenerating limb. This means that the animals will still develop normally and grow legs, but that later on we want to be able to get rid of specific genes in the regenerating legs and then see if they can still regenerate. We’re using localized “gene-editing” technologies like CRISPR (Clustered, Regularly Interspaced, Short Palindromic Repeats) and TALENs (Transcription Activator-like Effector Nucleases) to do this.
In your opinion, why is BWH a good fit for your research?
JW: BWH is a premiere medical center. In orthopedic surgery, people are getting joints replaced and fractures fixed every day. It’s exciting to be a part of extending that outlook into the research domain, because doing research is how we make progress so that some day conditions that have no great treatment now might become treatable. I love the setting of a university since I love to teach. But with a hospital, there’s the feeling you get when you walk through the hall that what you’re doing in the lab could have the double benefit: besides just pushing the boundaries of human understanding and satisfying curiosity, what you’re doing might actually help people some day. This is truly salient at a hospital.