Researcher Sally Moody uses frog embryos to clear the knowledge gap in neural regeneration
Sally A. Moody is a lab rat. She works with frogs in service to the world’s mammals, especially the two-legged kind. If her research at GW reaches its full potential, it will mark a significant breakthrough in neural regeneration through the manipulation of stem cells.
Sally Moody, Ph.D., a professor of anatomy and regenerative biology at the George Washington University School of Medicine and Health Sciences, is currently exploring the cascade of interactions that instruct lineages to give rise to the frog nervous system. In collaboration with fellow GW professor and GW Institute for Neuroscience Director Anthony-Samuel LaMantia, Ph.D., Moody is trying to determine whether what she has learned about manipulating a gene in the frog embryo is applicable to mouse embryonic stem cells.
The 60-year-old personable, tattooed (yes — more on that later) former music major, who grew up on a dairy farm in upstate New York, is celebrating the 30th anniversary of her lab, which she began at the University of Virginia as an assistant professor. To fully appreciate Moody’s dedication to her lab, let’s reflect on the story of Max Mandelbaum. Last year, Mandelbaum, an eager GW freshman from the Philadelphia suburbs, signed up for a stem cell course that Moody was offering. Unfortunately, he was the only enrollee, so Moody offered him a choice of dropping the course or taking a one-on-one seminar with her each Wednesday.
Mandelbaum was amazed. “I think most professors would have just canceled the course,” he said later.
One Wednesday, Mandelbaum found Moody’s office door locked. “I had simply forgotten,” she explains, “so he tracked me down in the lab.” Moody explained she was working with frog embryos and the student was enthralled. And that’s how Max Mandelbaum became one of three undergrads now working for credit in her lab. “I’m trying to get him a grant so he can work in the lab this summer,” Moody says. “He’s very gung-ho.”
Mandelbaum says his career path has changed. “I was originally focused on med school,” he says, “but the more I work in her research lab, the more I’m thinking of getting a Ph.D. and pursuing my own research.”
Moody spends a lot of time with her undergrads, teaching them how to do research and working with them at the bench. “I really enjoy this,” she says. “I had a similar experience as an undergrad doing independent research — once I figured out I wanted to do biology.” In fact, if not for her wanting to escape rural New York and having a lack of confidence in her own musicianship, the world might have lost an eminent researcher.
Her desire for independence led Moody to leave high school after her junior year after being accepted early by Goucher College in suburban Baltimore. Halfway through her second year, Moody says, she “realized there was no way I was ever going to make a living as a music major because I wasn’t that good.” The longtime self-described “science nerd” switched to biology and again graduated after only three years. Seeking financial independence, Moody finally landed a job as a lab tech in the anatomy department at the University of Maryland School of Dentistry. “They taught me to do histology and I loved it,” she says. “And they asked me if I wanted to get a master’s because they saw how interested I was.”
Moody did research in neuroscience under the tutelage of Richard Meszler, Ph.D., and her career path exploring the nervous system was launched. She earned her Ph.D. in neuroscience from the University of Florida and served a postdoctoral fellowship at the University of Utah until 1983. She then went to the University of Virginia and served on the faculty of the Anatomy and Cell Biology Department, the Department of Neuroscience, and the Developmental Biology program. She came to GW as a full professor in 1994.
Working with a gene called FoxD4 in Xenopus laevis, the African clawed frog, Moody and her team wanted to influence a cell that would otherwise make gut or skin to instead make nervous system.
So what goes on in her lab? Moody and her team are working on two grants from the National Science Foundation and the National Institutes of Health. Working with a gene called FoxD4 in Xenopus laevis, the African clawed frog, Moody and her team want to influence a cell that normally makes gut or skin to instead make nervous system. “What we’re trying to do is understand how an embryonic cell makes the decision to become a neuron,” she says. “It doesn’t have to do with the frog’s nervous system; the frog is just the medium in which it’s easiest to do the experiments. When they start out, embryonic cells are pluripotent — that is, they can make lots of different tissues. So it’s those early decisions we’re trying to parse out, really looking at a network of genes and how they interact to cause this conversion of a cell that can make anything to a cell that can only make nervous system. That’s pretty cool.”
The collaboration with LaMantia’s lab “grew out of our shared interest in the early steps of specifying neural stem cells,” says LaMantia. “Sally had done pioneering work on a family of genes, the forkhead or Fox genes, that she had shown clearly were key for neural stem cell identity in the frog. My colleagues and I found that the mouse equivalent of one of these genes had a dramatic increase in expression just as the forebrain — the part of the embryonic brain that will make all of the regions that do the ‘heavy lifting’ of cognition, learning, and memory — becomes distinct as a defined region. I think we really have been able to establish an approach that will allow us to begin to sort out just what the ‘switches’ are that direct a stem cell to become a neural stem cell.”
Also in Moody’s lab, research scientist Bo Yan, M.D., Ph.D., professor of Anatomy and Cell Biology and of Genetics, is working on a two-year grant from NIH’s National Institute of Dental and Craniofacial Research, for its project on identifying novel genes involved in neural tube and craniofacial birth defects.
If the research gods smile upon Moody’s work, scientists will be able to control development of embryonic cells, whether they are in an embryo or a stem cell, and to force them to make neurons in a controlled way. “We want to control their gene expression so that they make neurons, which would be useful for regenerative medicine,” says Moody. “This could be used to replace neurons in damaged neural tissue, as occurs in stroke — to grow replacements and then transplant them. It’s a long way off, but that’s the ultimate goal.”
Throughout her research, Moody continues to teach — in school, in her lab, and outside the university. Not long ago, she was giving a talk at an elementary school not far from the Rockville, Md., home she shares with her husband, Steven L. Klein, an NSF program director. Moody was wearing sneakers with low-cut socks, and suddenly one of her young listeners burst out: “Oh. My. God. She has a frog on her leg!”
Moody raised her pant leg above her right ankle, so everyone could see. Sure enough, it was a blue-ink tattoo of Xenopus, the product of a mother–daughter bonding experience with daughter Rachel at a Gaithersburg tattoo parlor.
Some folks wear their heart on their sleeve, metaphorically. Sally Moody carries visible testimony of her devotion to research with every step she takes.