You are here

Randall Moon and Merrill Hille featured by ISCRM

Wednesday, June 26, 2019 - 13:00

Original article on the Institute for Stem Cell & Regenerative Medicine website

Wandering has always been a way of life for Dr. Randall T. Moon. Born in Rhode Island, and raised in a one-stoplight town in the countryside of northern Ohio, he completed high school in three years, as valedictorian, then left the rural setting as quickly as possible. In his first year of college, he dropped out of three schools in three quarters. A phone call from a recruiter promising a very liberal arts education and sunny weather drew him to New College, a small school in Florida with an eclectic list of bragging points: high faculty-to-student ratios, a campus designed in part by I.M. Pei, sweeping views of Sarasota Bay, and a worldview that favored student-driven intellectual pursuits. All of which suited Moon perfectly.

At New College, Moon found a model teacher in Professor John Morrill, a renowned figure with a sterling reputation in cell and developmental biology and a knack for inspiring hard work and affection from his students, several of whom would become members of the National Academy of Sciences. Morrill soon hired Moon as a teaching assistant, providing a source of income that allowed the financially-strapped student to stay in college.

Flush with energy and access to a full lab, Moon was inspired to focus on developmental biology by watching marine invertebrate embryos develop under microscopes. Then, at the age of 21, Moon was diagnosed with metastatic thyroid cancer. The subsequent surgery and radiation treatments led the college senior to conclude that standard medical interventions were lagging too far behind advances in biology – something he never forgot.

It was Moon’s love of biology that propelled him forward after cancer treatment. After receiving his B.A. from New College, Moon applied to only one graduate program, the Department of Zoology at the University of Washington. (He was drawn to UW, in part, by the prospect of studying at the Friday Harbor Marine Station in the picturesque San Juan Islands, where he would eventually complete a five-week course on Marine Invertebrate Development – not his last encounter with marine animal life.)

Moon recalls that the transition from the freedoms at New College to the more structured culture at UW was a rough transition. “At New College, nobody was going to tell you what to do. The faculty were there to help you in whatever direction your interests took you, and to make suggestions, not to issue edicts. To go from that to a relatively regimented environment wasn’t easy.”

Nonetheless, the admissions committee must have seen abundant promise in Moon. Despite his refusal to take the GREs because the exam didn’t measure creativity, and despite holding a diploma from a college that gave written evaluations instead of grades, the university welcomed Moon to the doctoral program in Zoology. Over time, the student and the school learned to adapt to each other. Under strict orders from the department to find an advisor by the end of the first year, Moon sought out a kindred spirit. “I had the good fortune to pick Merrill,” he says.

Merrill Hille became Moon’s PhD advisor in 1978 and remains a close friend more than forty years later. During opening remarks at the 2019 Randall T. Moon lecture, Hille spoke of Moon’s career with a mentor’s pride – the seven papers he published as a graduate student and seven more as a postdoc, the joy he found studying embryos, and his groundbreaking insights into the Wnt signaling pathway.

In Hille’s lab, Moon studied protein particles that were thought to regulate early gene expression in sea urchin embryos. His natural curiosity took him on separate trips to England, and to Palermo, Sicily, where he spent months with local researchers seeking, as always, new perspectives and the excitement of new situations. Hille says she knew from Moon’s performance in her lab that he was going to be productive.

“One of his solo published papers in my lab started as an assigned paper he submitted to a course on mouse development. It was so good, the professor told him he should submit it for publication. That paper, among many others, showed Randy’s expertise as a researcher and a writer. He was a voracious reader, at a time before the internet when you actually had to go to the library.”

Moon earned his PhD in 1982. He was soon on the move again. For the next three years, home would be Caltech, in Pasadena, California, where he worked as a postdoc, focused on Molecular and Cell Biology, in the lab of Elias Lazarides. After this brief and highly productive postdoctoral period, he was recruited back to UW to join the Department of Pharmacology in the School of Medicine as an assistant professor.

Defining the Wnt pathway was a landmark moment for science, and an early career milestone for Moon, a stepping stone to becoming a Howard Hughes Medical Institute investigator, an elected fellow of the American Association for the Advancement of Science, a member of the American Academy of Arts and Sciences, and a member of the National Academy of Sciences.

At the UW, Moon and a legion of students learning alongside him continued to ask probing questions of the mysterious Wnt molecules that he and Andy McMahon had stumbled on years earlier. Questions about the role of Wnt signaling in early development, in regeneration, and in diseases all led to game-changing insights into Wnt signaling, published in dozens of prestigious publications for all the world to read.

By the early 2000’s other advances in developmental biology were reshaping the landscape of science and medicine. Embryonic stem cells – and soon, their less controversial cousins, induced pluripotent stem cells, were giving researchers new tools to study diseases, particularly those rooted in cellular deficiency (or excess), like Alzheimer’s, heart disease, diabetes, and cancer.

At the University of Washington – in the cradle of stem cell medicine – Moon sensed an opportunity to harness this massive latent potential by creating a new institute that would galvanize scientists working in multiple disciplines across biology, engineering, and pathology. Moon’s mission was also shaped by his personal experiences – first as a thyroid cancer survivor, then as a patient coping with Parkinson’s Disease (he was diagnosed in 2003). More than ever, the scientist was determined to make a lasting impact on patient care.

For years, serendipity had served Moon well, leading him to unexpected discoveries in and out of the lab. Now, he sought support for his vision for a new stem cell institute with single-minded focus. He found allies in Charles Murry and Tony Blau, two physicians who shared Moon’s enthusiasm for a facility that would allow researchers and clinicians to pursue breakthrough medical therapies collaboratively.

“From the beginning, Randy’s vision was that the institute needed to focus on developing new treatments for today’s patients,” says Murry, UW Professor of Pathology, Bioengineering, Medicine/Cardiology, and the current Director of the UW Medicine Institute for Stem Cell and Regenerative Medicine (ISCRM). “It was hugely influential that the most basic scientist among us advocated for stem cell therapeutics. Coming from physicians like Tony and me, this might have appeared self-serving or naive. Today, Randy’s vision has become part of our institutional DNA.”

Back in the early 2000’s, Moon, Murry, and Blau were swimming against powerful currents. Politicians at all levels of government were questioning the morality of embryonic stem cell research, calling for moratoriums that continue to bridle the field. Undaunted, the three scientists advocated relentlessly for a stem cell institute, eventually finding a champion in UW President Mark Emmert, who backed his pledge with a public statement articulating the university’s support of stem cell research. Further backing came from the School of Medicine and Dr. Paul Ramsey, CEO of UW Medicine, executive vice president for Medical Affairs and dean of the UW School of Medicine. These critical endorsements turned the tide for good.

"President Emmert was decisive,” Moon recalls. “After hearing us speak about the potential impact of stem cell research on human medicine, he interrupted us and said, ‘This is a no-brainer. We have to do this.’ Dr. Ramsey was a constant source of support, and helped ISCRM find its new home. My chairman, William Catterall also played an essential role by serving on the Institute’s Scientific Advisory Board, and by helping to further solidify buy-in for ISCRM across the university.”

ISCRM, of course, is the Institute for Stem Cell and Regenerative Medicine, officially founded in 2006 with $23 million in private funding, much of it raised by Moon, who accepted an invitation from Dr. Ramsey to serve as the new institute’s first director.

“My enthusiasm for establishing ISCRM was based on the extraordinary potential of the institute to improve human health and on the leadership provided by Randy Moon,” says Dr. Ramsey. “As the young investigator who discovered the role of a protein (Wnt1) in creating a two-headed tadpole, Randy developed a truly outstanding research program that provides foundational basic science guidance for regenerative medicine. In addition to his outstanding personal research, Randy was passionate about bringing researchers together to advance the field of regenerative medicine. As the founding director of ISCRM, Randy recruited faculty from multiple disciplines, designed an ambitious and visionary agenda to improve health, and communicated his passion broadly, including assembling a large group of community leaders who have raised support from donors and from the state of Washington. UW Medicine is very fortunate that Randy Moon served as the founding director of ISCRM.”

Read the full article on the Institute for Stem Cell & Regenerative Medicine website

Fields of interest: