Dr. Jouni Uitto, Finnish ‘Father of Epidermolysis Bullosa Research,’ never finished with saving lives.
When Dr. Jouni Uitto arrived in Philadelphia from Finland on Labor Day morning in 1971, he thought he would stay in the United States for a year, maybe two, while he honed his research skills. Now, nearly 50 years later, “I’m still on the same trip,” says the renowned scientist with a deep chuckle that reaches his eyes. During his extended stay, Dr. Uitto cultivated national and international acclaim for his research on rare heritable skin diseases. His work in biochemistry and molecular biology has made clinical trials for potential therapies possible for two rare diseases that affect children. Along the way, he mentored and trained dozens of scientists, many of whom have become leaders in their fields. But before he set down roots as the chair of the department of dermatology and cutaneous biology at Sidney Kimmel Medical College—Thomas Jefferson University, he “meandered across the country” following the tug of promising research that ultimately led him back to the City of Brotherly Love.
Born and raised in Helsinki, Finland, Dr. Uitto stayed in his hometown for college and medical school. He graduated from the University of Helsinki with his MD in February 1970 and defended his PhD in biochemistry in the spring later that year. The double-doctor had known Finland all his life, but it was customary to go to the United States for a few years to develop as a scientist. “I came with the idea of going back to Finland and to do my clinical training there,” he says.
When Dr. Uitto landed in Philadelphia, set to begin a research fellowship at the University of Pennsylvania, his new boss greeted him with a surprising announcement. “Welcome to Philadelphia,” he says. “By the way, we are moving next summer to Piscataway, New Jersey, to Rutgers Medical School.” His advisor, Dr. Darwin Prockop known for his research on stem cells, collagen and connective tissue diseases, had just accepted the chairmanship of biochemistry there. He would become Dr. Uitto’s lifelong mentor, colleague and friend.
The moving notice did not ruffle Dr. Uitto, as he had planned to return to Finland after one year. But then research started going very well. An industrious young scientist, he worked “like crazy” from eight in the morning until eleven at night, six days a week. Dr. Prockop, who kept the same hours, appreciated the work ethic. But what he found truly remarkable about Dr. Uitto was his trainee’s ability to perform multiple experiments at the same time. “He kept at least three stopwatches around his neck to keep track,” recalls Dr. Prockop, who, at close to 90 years-old, still runs a stem cell laboratory at Texas A&M University.
“He also rode a bicycle to go to the men’s room about 300 feet away,” he added, “apparently to save time.” Dr. Uitto also “lit up the lab with his humor,” Dr. Prockop remembers, saying his protégé may have been pulling his leg with the bicycle. He was never sure.
For Dr. Uitto, that first year went by quickly. He was on track to publish a paper, so he stayed and moved with Dr. Prockop’s lab the following August to New Jersey. By the end of second year, he had another paper in the works, so he delayed returning to Finland again. The trend ballooned so that by his fourth year, Dr. Uitto had eight research studies to his name from the fellowship. He stayed for about five years, researching how cells make collagen, a vital protein for skin and joint health, and one of the most abundant proteins in the body. He also began to uncover mutations in collagen genes that cause disease.
Despite the long hours and substantial publication output, Dr. Uitto’s merry demeanor helped keep spirits high. “We laughed when the experiments turned out as we planned,” Dr. Prockop says. “We laughed even harder when they did not and the results clearly showed we were foolish to have undertaken such experiments.”
Five years into his one-year research fellowship, Dr. Uitto was hooked. But he wanted to finish medical training. “I decided …now I have to go back to clinical training or it’s going to be too late,” he says. But rather than returning to Finland where residency lasts five years, he opted to stay in the U.S. where clinical training was only three years and he could spend about half of his time doing research. The decision brought him to the Midwest, where he completed his residency in dermatology at Washington University School of Medicine in St. Louis and then joined the faculty there.
But about a year and a half into his faculty appointment, Dr. Uitto caught the California bug, he says. He moved to Los Angeles to join the faculty at UCLA in 1980 and immediately fell in love with the place. “We lived right on the beach, overlooking the Pacific,” he recalls. How much he savored the views emanates in his voice as he reminisces about those years on the west coast. Dr. Uitto soaked up the sun in California for almost eight years at UCLA, with the exception of a notable one-year sabbatical to New Jersey that changed his career.
In 1978, the National Institutes of Health awarded Dr. Uitto a Research Career Development Award that provided funding for five years. The stipulations of the grant strongly encouraged its awardees to spend their last year on the grant learning something new from researchers outside their wheelhouse. “Usually people go to nice places—Rome or California, for example,” Dr. Uitto says. “Guess what? I went to New Jersey,” he laughs in good-natured disbelief. “That was the smartest move in my career.”
To Dr. Prockop’s delight, Dr. Uitto returned to his lab at Rutgers for a sabbatical year in 1982. The field of molecular biology was in its infancy, poised to revolutionize medical research. During his sabbatical, Dr. Uitto learned how to extract DNA from cells and tissues and analyze the genetic material using the cutting-edge techniques of the time, like Sanger sequencing, gene cloning and PCR.
Before his journey to New Jersey, Dr. Uitto’s lab revolved around protein chemistry. They used radioactive isotopes to measure the rate of collagen production in scarring diseases. But “when I went back to California, I changed my entire lab,” he says. No more protein chemistry. It was now all DNA.
“We were the first in the world in dermatology to do that, to adopt these new molecular biology techniques,” he says.
After a few years back in California, Dr. Uitto received a call from Jefferson Medical College. “I had no idea what Jefferson was actually. I’d never visited,” he recalls. “They asked if I’m interested in the chair here and I said, ‘Nah.’” But after talking it over with his wife, also a scientist, and some encouragement from Dr. Prockop, who had recently joined the Jefferson faculty as the chair of Biochemistry and Molecular Biology, the couple decided to go back to the east coast “for a few years,” to expand their academic standing and then return to California for senior positions. That was the plan. The year was 1986.
“I just passed 32 years here at Jefferson as a chair, which has been very good professionally,” Dr. Uitto says.
When Dr. Uitto came to Jefferson, he brought some of his clinical colleagues from California with him. They set up the clinical side. He set up the research side. The department grew quickly and currently consists of 27 full-time faculty, half of whom focus on research and half of whom run the clinical operations. The department’s growth and distinguished reputation is thanks in no small part to Dr. Uitto’s efforts to build up the university’s national and international recognition in the field of dermatology. The molecular biology techniques he adapted from the sabbatical year in Dr. Prockop’s laboratory and continued to develop in the Jefferson Institute of Molecular Medicine, originally directed by Dr. Prockop, attracted research fellows and collaborators from all over the world. Dr. Uitto has trained more than 140 research fellows from 28 countries, 16 of whom, upon return to their native countries, became chairs of their departments in their respective fields. His trainees have returned the favor: Dr. Uitto is the recipient of several honorary doctorate degrees, and he holds a number of visiting professorships around the world. These approaches also form the basis of ongoing collaborations, often with his previous trainees in the global setting. Although the numbers of Dr. Uitto’s trainees are impressive, the quality of his mentorship is deep.
“His mentorship underpinned my own emerging values of commitment, drive, focus and determination to discover new science, new data and new ways of research that could benefit patients,” says Dr. John McGrath, a professor of molecular dermatology at King’s College London, who was one of Dr. Uitto’s trainees right in the thick of the research revolution in the mid-90s. Although it has been nearly 25 years since Dr. McGrath worked in Dr. Uitto’s lab, the two collaborate and regularly meet. “It’s almost like I have never left his lab,” Dr. McGrath says.
In a career of vast achievements, Dr. Uitto is most proud of training the next generation of scientists.
“There is certain satisfaction to see that you keep the field growing. They are your trainees who are now continuing the research,” he says. “That’s the kind of legacy you want to have.”
The molecular laboratory research techniques Dr. Uitto brought to Jefferson also propelled the other greatest achievement of his career: working with patient advocacy organizations for two serious rare diseases.
When Dr. Uitto came to Jefferson, hardly anything was known about a group of genetic diseases called epidermolysis bullosa (EB) that make the skin very fragile. The diseases manifest at birth with extensive blistering and scarring. In the most severe form of the condition, the skin is so delicate that it sloughs off and many children die from infections and metabolic disturbances during the early few weeks or months of life.
“Dr. Uitto has had a huge influence on therapy development and progression,” says Brett Kopelan, executive director of the Dystrophic Epidermolysis Bullosa Research Association of America (DEBRA), a New York-based patient advocacy organization. “His lab was the first to find the genetic basis of the disease, which now has five gene therapy approaches in clinical trials that all tie back to him,” notes Kopelan, who calls Dr. Uitto the grandfather of EB research.
In a series of studies published in the early 90’s, Dr. Uitto’s research group began to uncover the genetic roots of the disease. The scientists identified potential disease-causing genes from families with a milder form of the condition. Then Dr. Uitto capitalized on his sabbatical training. “These new technologies really gave us a jumpstart for our research,” he says. The researchers were able to make copies of candidate genes to study. They soon found mutations in a gene called collagen7A1 that underlie the condition. The gene makes a protein that helps hold layers of the skin together, and EB patients do not make enough of it. Now, families can request prenatal genetic testing for the condition, and Jefferson was the first in the world to make this mutation detection available.
Dr. Uitto quickly built on these discoveries to develop a transgenic mouse model of the disease that recapitulates the clinical features. The mice have served as platforms to develop treatment approaches and laid the foundation for clinical trials.
“Dr. Uitto always has the ability to see the most important path toward therapy development,” Kopelan says, adding that as a distinguished researcher, Dr. Uitto has “a global presence. Everybody knows him, respects him, and either has or wants to work with him.”
Sharon Terry, founder and executive director of PXE International, an advocacy organization for a rare disease called pseudoxanthum elasticum (PXE), agrees. “His ability to accept and embrace a patient advocacy group was far ahead of his time,” she says. “Now it’s fashionable, but …he really led the way amongst researchers in bringing respect to that kind of work.”
Terry and her husband reached out to Dr. Uitto in 1995, just after their two children were diagnosed with the disease. PXE causes mineral build-up in elastic fibers of the skin and blood vessels. The first sign of the condition is often small slightly raised yellowish bumps on the neck or the skin under the armpit. The disease can lead to build up of plaques in blood vessels and eyes, causing early heart attacks and blindness. Mutations in a gene called ABCC6 cause more than 90 percent of cases. But that was unknown in the mid-90s.
“Nothing was known about the disease,” Dr. Uitto says. “What’s causing it, what the prognosis is, even the hereditary pattern was not clear.” The Terrys went to the library and searched through the scientific literature for someone who might help.
“We called Dr. Uitto and right away he says, ‘Yes, come see us,’ and makes an opening for us and our kids to meet at his lab. That was quite remarkable,” Terry says. “He took us seriously.”
“Dr. Uitto always has the ability to see the most important path toward therapy development”
The Terrys asked Dr. Uitto what he needed to get to the bottom of the disease. Dr. Uitto made a tall request: DNA from 400 families with PXE. The condition is rare, only affecting about one in 50,000 people worldwide. Dr. Uitto did not think he would see the Terrys again, but about a year later, they returned. In the intervening year, the couple had quit their jobs and established PXE International. Then, they went on the web and solicited patients. They quickly identified 4,000 families with PXE in the United States and provided Dr. Uitto’s lab with DNA from 400 of them.
The researchers found the gene relatively quickly. “We can now actually look into the types of mutations and predict how severe the disease is going to be and what’s the overall outcome,” he says. The disease still wants for a cure, but “Dr. Uitto really has made it possible for us to be on the cusp of several therapeutics and every step of the way, his lab has been ahead of the curve,” Terry says.
Finnish, Not Finished
And it seems there is still no stopping him. Just as he started his post-doctoral fellowship some 48 years ago, Dr. Uitto remains a publishing powerhouse. In the past year, he has published more than 30 papers in collaboration with colleagues, adding to his biography consisting of well over 700 original, peer-reviewed research publications and hundreds of reviews and expert commentaries.
“I enjoy what I’m doing,” he says. “As long as my health is good, I really like what I do and get satisfaction from it.”
Perhaps, Dr. Uitto will take after his mentor Dr. Prockop and continue to follow the pull of curiosity to make new discoveries for years to come. The dermatology field and patient advocacy groups are hopeful that’s the case. Dr. Uitto is the leader of a remarkable, global research community recognized not only for his incredible scientific contributions, but also his welcoming demeanor. “He can make people feel they’re being seen and heard,” Terry says. Kopelan echoes the sentiment. “He makes sure people are comfortable and have an atmosphere where it’s easy to be together and most importantly collaborate.”
“If I had my way, Dr. Uitto would be in EB research at Jefferson for the next 40 years,” Kopelan says. “Thankfully, I don’t see him walking off into the sunset anytime soon.”
Dr. Uitto does not think so either.
“I’m Finnish, but not finished, yes, absolutely,” he says with a deep laugh.