Search Magazine July 06, 2015

Big thinker

Nadia Rosenthal, Renaissance Woman

A superb scientist, a keen intellect, an outstanding teacher, a visionary leader — this is how others describe Nadia Rosenthal, who is taking on a newly created role to lead The Jackson Laboratory’s mammalian genetics headquarters in Bar Harbor.

“The most impressive thing is that Nadia rolls all of these qualities into one. She integrates those characteristics so that the end result of any of her projects is not just a technical tour de force, but also something that elevates the entire scientific team to a higher level,” says JAX President and CEO, Edison Liu. “That’s the hallmark of a visionary leader, and we are just very fortunate to have her join JAX.”

In March, Rosenthal was named scientific director of JAX’s Bar Harbor campus. As she begins her transition to JAX from her post as founding director of the Australian Regenerative Medicine Institute (ARMI) of Monash University in Melbourne, she brings with her a wealth of expertise and experience. Rosenthal is a world-renowned leader in mammalian genetics, with a particular focus on the mouse as a model organism. She has made fundamental contributions to multiple areas of biology throughout her career, including cloning and sequencing the insulin gene,  unlocking the biology of muscle cell differentiation, discovering novel aspects of heart development, and harnessing stem cells for regenerative medicine.

In addition to her diverse scientific talents and far-reaching knowledge, Rosenthal also has a knack for growing and leading scientific organizations. In 2001, she moved to Rome to build a mouse biology program for the European Molecular Biology Laboratory (EMBL), a highly distinguished research organization dedicated to molecular biology research. Recognizing the power of the EMBL model, particularly for attracting and cultivating young researchers, Rosenthal helped disseminate it to other parts of the world by establishing the first non-European EMBL outpost in Australia. By the end of this year, there will a dozen such groups across the continent. She also created ARMI at Monash University and served as its founding director. First launched in 2009, it is now a prominent institute for research on stem cell biology and regeneration.

“She really has a talent for inspiring others to collaborate toward a common goal. She knows what needs to be done and will work with people so that it’s a win-win situation,” Liu says.

Melding art and science

artAlthough her achievements in science might suggest otherwise, Rosenthal began life with decidedly different proclivities. Her parents were classically trained musicians, and she spent her childhood surrounded by artists, poets, musicians and playwrights. As she grew up, the glamour and glitz of Hollywood and the bright lights of Broadway became familiar scenes.

Her own interests in art were wide-ranging. “I was insatiable — I sculpted, I drew, I painted,” she recalls. She tried her hand at nearly every art form, from painting in the style of photorealism to modern sculpture to bookbinding. Art was more than just a broad passion, though. It was also a gateway to Rosenthal’s scientific pursuits. Through her artwork, she became fascinated by the extraordinary patterns that exist in nature and sought to understand why things were the shape they were. In high school, an inspiring teacher gave a captivating tour of the biological world, teaching everything from hard-core biochemistry to plant and animal phylogeny.

“I just lapped it up because of the way she taught it. She made it relevant,” says Rosenthal. “And I became obsessed with the idea, with all of this detail she taught me, that I would be able to translate it into an understanding of pattern formation, which was the thing I was really interested in.”

Although Rosenthal had studied science before and enjoyed it, that advanced biology class marked a real awakening, setting her on a path to study how form emerges — a central question in the field of developmental biology.

Globetrotter

As Rosenthal finished high school and contemplated her undergraduate studies, she was particularly drawn to the style of university education in the United Kingdom, which allowed students to focus, almost single-mindedly, on one area of study to the exclusion of other subjects. To Rosenthal, that seemed a perfect fit. Her education had been fairly liberal up until that point; as a rising undergrad, she felt ready to focus on science. So she enrolled at the University of North Wales in Bangor, U.K.

Soon, though, her wide-ranging interests and curiosity got the better of her, and she found herself gravitating toward courses in French literature and ancient Greek architecture. Rosenthal also realized that her scientific training was not heading in the direction of her true love: developmental biology. She eventually returned to the U.S., and landed at Harvard University, where she completed her undergraduate degree and also earned her Ph.D.

While the academic environment at Harvard proved challenging, even grueling, at times, it was also deeply formative. The field of molecular biology was booming, and the ability to isolate and decode individual genes had just hit the scientific scene. “It was so powerful and so compelling, I felt that if I didn’t learn it, I would lose the opportunity to apply all these molecular tools to the questions of development,” Rosenthal recalls. She shelved her pursuit of developmental biology and fully dedicated her efforts to gene hunting. That meant shifting her work with her graduate advisor, Fotis Kafatos, to the laboratory of a nearby faculty member, Walter Gilbert, who pioneered one of the two pivotal DNA sequencing methods of the day. Gilbert’s lab was engaged in an intense race to sequence the full genetic code of the insulin gene. Rosenthal recalls the experience as both intense and exhilarating. “We felt like we were the center of the universe, scientifically.”

Although her work cloning genes may have seemed far-flung from development, it motivated her later efforts to study how genes are turned on and off — a key aspect of developmental processes. At the time, little was known about how genes were regulated in humans. As a postdoctoral fellow at the National Institutes of Health, she identified a key regulatory component — the first enhancer element in humans — using homology searching, a technique that fishes out similar stretches of DNA from even distantly related organisms, purely on the basis of shared genetic sequences. Her landmark discovery was published in Science in 1983.

In addition to catalyzing important scientific discoveries, Rosenthal’s days at Harvard also instilled in her a deep sense of scientific community, particularly the importance of peers.

“It is really important to know whom you are traveling with in life,” she says, “and scientists are some of the most interesting people out there. My best friends have invariably been scientists because we share that love of the embryo, or something we’ve seen down the microscope, or the thrill of the chase, or the sense of wonder.”

Committed to mentoring

While Rosenthal has earned many accolades throughout her career, she is particularly proud of the cohort of young scientists she has helped train. She has mentored over 60 graduate and post-graduate trainees over a span of more than 30 years. Not all have remained at the laboratory bench, but almost all have pursued a path in a science-related field. “That means a lot to me,” she says, “because it means that I have managed to get people through some difficult times in their lives as students and postdocs, and steer them toward productive areas of science.”

Rosenthal’s teaching extends well beyond the laboratory. As a graduate student at Harvard Medical School, she taught biochemistry to medical students. In the classroom, she often drew upon her own artistic capabilities, arriving at lectures a half-hour early so she could illustrate complex metabolic pathways in exquisite detail on the blackboard using multi-colored chalk. Her students would ask for photocopies, but she refused, insisting instead that they draw the diagrams for themselves with the colored pencils she provided to each student. “If you draw it yourself, it is in your hand. And your eye-hand connection somehow emblazons it in your brain and it is a lot easier to remember,” she says.

She also authored a textbook on heart development. Enticed by the beautiful morphology of the embryonic heart, Rosenthal became deeply interested in the development of the heart and decided to co-write a book on it — now widely considered the bible of the field.

A champion for mice

With JAX’s rich legacy of innovation and discovery in mouse genetics, it is fitting that Rosenthal was lured to the organization by her own love of the mouse as a model organism. Like many scientists who choose the animal as their laboratory muse, Rosenthal has often worked with strains that are highly inbred — mice mated together other over many generations, making them genetically homogeneous. Such genetic similarity is a boon for biological studies, enabling researchers to replicate results across multiple experiments and untangle the effects of genes from those of the environment.

But these advantages come at a cost. By minimizing genetic diversity in the mice they study, scientists may neglect the very features that can be helpful in understanding complex traits in humans, such as aging or susceptibility to diabetes.

“There is a lot of genetic diversity in the human population, so if you are trying to model a genetically diverse population with a basic inbred mouse, you are really coming up short,” explains JAX Professor Gary Churchill, who has devoted the last decade to creating a vast repository of mouse strains, about 150 in total, that have been painstakingly bred to maximize their genetic variability. This resource, known as the Collaborative Cross, is proving to be a powerful tool for unlocking key aspects of human biology — by studying the mouse.

Rosenthal recently screened a portion of the mouse collection pioneered by Churchill, searching for differences in the ability to regenerate heart tissue following a heart attack. The results were astonishing. “I was stunned at what we got; the results were all over the map. Some animals recovered from heart attacks just like that and others repeatedly did not, in fact, they did terribly,” she notes.

Others have unearthed surprises, too. A recent study published last fall in the journal Science shattered the long-held view that Ebola infection cannot be effectively studied in mice. The animals have been excluded from Ebola research because no one has been able to reproduce the hallmark symptoms of the viral infection. But using mice from the Collaborative Cross, a research team led by scientists at the University of Washington demonstrated a range of responses to Ebola in mice, from resistance to infection to hemorrhagic fever to systemic organ failure, recapitulating what is seen in the human form of the disease.

Rosenthal sees these findings as just the tip of the iceberg, particularly when it comes to studying human disease. “This is a golden opportunity for JAX to really showcase all of the mice in the cupboard, not just the ones that people think they need.”

As Rosenthal takes the helm in Bar Harbor, she will be championing this scientific approach and ensuring that JAX’s scientific services are poised to fully realize the promise of a new era of mouse genetics. She will also serve as a mentor and advisor for JAX faculty in Bar Harbor, helping to shape their research and provide a cohesive vision that unifies their work.

Indeed, Rosenthal is no stranger to Bar Harbor and its surroundings. As a child, she spent summers in the area, so her appointment at JAX is a kind of homecoming. “I have a deep, deep affection for this part of the world. Like a sailor who has been around the world, you bring the world with you in your head.”

And it is no surprise that she is embracing her new role with the same gusto as in her previous feats, undeterred by the risks and challenges that can accompany change.

“I am going to change my direction again by coming to JAX,” she says. “I’m proud of the fact that I’m not scared of changing — it’s the change that makes you learn.”


Nicole Davis, Ph.D., is a freelance writer and communications consultant specializing in biomedicine and biotechnology. She has worked as a science communications professional for nearly a decade and earned her Ph.D. studying genetics at Harvard University.

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