Charting new paths


Neuroscientists chart paths toward viable therapies for neurological diseases

In 1983, during her pediatric residency at Texas Children’s Hospital, Huda Zoghbi, MD, saw her first patient with Rett syndrome, a nonverbal 5-year-old girl who couldn’t stop wringing her hands. Mysteriously, the patient had been healthy until the age of 18 months, when she became withdrawn, avoided eye contact and eventually stopped talking. The encounter profoundly changed the young pediatrician and set her on course for a career uncovering the genetic causes of pediatric neurological conditions. Today, Zoghbi is the founding director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine, a Howard Hughes Medical Institute investigator and the Ralph D. Feigin, MD, Endowed Chair in Pediatrics.

Under Zoghbi’s transformational leadership, the NRI is unlocking the genetic and molecular mysteries behind developmental and neurodegenerative brain disorders in both children and adults. Dedicated to improving the lives of patients facing these devastating neurological disorders, the NRI is a basic research institute committed to understanding the biological mechanisms that lead to neurological diseases in order to develop effective treatments. In addition, the remarkable discoveries emerging from NRI offer hope for children and families facing rare and devastating neurological disorders like Rett syndrome.

Early career

Born and raised in Beirut, Lebanon, Zoghbi was a first-year medical student when civil war broke out and forced her to immigrate to the United States.

“Dr. Ralph Feigin recruited me to the pediatric residency program at Baylor College of Medicine and taught me clinical scholarship,” Zoghbi said. “Dr. Marvin Fishman, an exemplary clinician, then inspired me to become a pediatric neurologist, and I met the patients who changed the course of my career.”

As a young physician, Zoghbi found it heartbreaking to watch patients, young and old, lose their lives to neurological diseases. She realized that to truly help these patients, she needed to better understand the root causes of their illnesses. She turned to Dr. Arthur Beaudet, one of the finest geneticists in the country. When Dr. Beaudet took Zoghbi into his lab, it was the beginning of her career in research — moving from her clinical role to become one of the world’s leading investigators into the genetic basis of neurological disease.

“I turned to research for answers, and today, together with numerous collaborators and trainees, we are charting new paths toward viable therapies,” Zoghbi said. “There is still a long way to go, but it is thrilling to see that we are beginning to understand the language of life and translate it to help mankind.”


International recognition

Now an internationally recognized neurogeneticist, Zoghbi has received numerous honors for her pioneering work, including the prestigious Breakthrough Prize in Life Sciences. Established by Silicon Valley leaders including Facebook co-founder Mark Zuckerberg, the Breakthrough Prize recognizes paradigm-shifting research, celebrating scientists and generating excitement about science as a career. Zoghbi was honored for her discoveries of the genetic causes and biochemical mechanisms of Rett syndrome, as well as those of spinocerebellar ataxia, which generally appears in adulthood, destroying brain cells that control balance and breathing and usually killing patients within 10 years of the first symptoms.

Zoghbi has donated most of the $3 million prize to advance genetic and neuroscience research and to inspire and support the next generation of investigators.

Since the nationally televised Breakthrough Prize awards presentation in December 2016, Zoghbi has been flooded with an overwhelming response from a wide-ranging community extending far beyond her colleagues, family and friends.

“The messages I have received showed me how the Breakthrough Prize presentation ceremony humanized the process of science for so many young people, especially young girls,” Zoghbi said. “Some said they are now excited about a career in science. Some messages were from parents who said the televised ceremony gave them the opportunity to sit down with their children and talk about a career in medicine or science.”

And it wasn’t just the messages involving young people that touched Zoghbi. “I have so many emails from immigrants who said how proud they were and how they related to my journey, not just in science, but in being a successful, valued part of this country,” Zoghbi said. “Since I am an immigrant myself, these really touched me.”

In Hong Kong earlier this year, Zoghbi was awarded the international Shaw Prize in Life Science and Medicine, an honor she shared with University of Edinburgh geneticist Sir Adrian Bird. The award recognized their discovery of the genes and encoded proteins that identify one chemical modification of the DNA of chromosomes that influences gene control as the basis of Rett syndrome.

The Shaw Prize honors individuals who have recently achieved significant breakthroughs in academic and scientific research and whose work has resulted in a positive and profound impact on mankind.

Building on the future

The investigators at the NRI are continuing to gain insight into the underlying causes of numerous neurological and neuropsychiatric disorders and are developing new therapeutic targets to treat them. So far, most genetic disorders can’t be cured, but once the causes are discovered, treatments sometimes can prevent or manage the disorders caused by genetic abnormalities.

Many NRI investigators are physicians or physician-scientists whose patients inspire the time-consuming basic research necessary to move forward toward more effective therapies. Discoveries in the pediatric arena have led to breakthroughs in adult neurodegenerative and neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, bipolar disorder and Amyotrophic lateral sclerosis (ALS), conditions which affect millions of people.

The NRI brings together faculty with unique and complementary expertise representing a wide range of disciplines, all focused on solving previously intractable problems in neurological disorders and disease. Engineers, mathematicians, statisticians and computer scientists work closely with geneticists, neuroscientists, neurologists, pathologists, neurophysiologists and neurosurgeons. The environment is open and generous, encouraging robust interaction between formerly isolated fields.

Through these innovative, multidisciplinary collaborations, the NRI is bridging the gap between initial gene discovery and clinical applications, with the ultimate goal of developing effective treatments for a broad range of disorders.

Cultivating the next generation of scientists

According to Zoghbi, when she began her career more than 30 years ago, it was much easier to pursue bold research ideas.

“It wasn’t as hard to get funding, and we didn’t feel the same pressures young scientists face today,” she explained. “I had no research experience when I decided to study genetics, but Dr. Beaudet took me into his lab anyway. That would be very hard to do today.”

With this in mind, Zoghbi has established a special fund at the NRI to support the next generation of scientists by giving them room to pursue creative ideas as they are beginning to launch their independent research careers.

“The transition to independence is the most difficult period in a young scientist’s career,” Zoghbi said. “This kind of funding gives them a measure of freedom and signals our faith in their abilities to carve out their own niche.”

The NRI mentorship fund will provide one year of support to postdoctoral fellows who want to test bold hypotheses that would not be supported through conventional grants. Zoghbi started the fund when she received the Gruber Prize in Neuroscience, shortly after the NRI first opened in 2010. And she has grown the fund substantially through subsequent donations from additional prizes and awards, including the Shaw Prize and the Breakthrough Prize. Zoghbi hopes that support from this fund, combined with hard work and protected space for intellectual freedom, will ensure the success of many young scientists poised to embark on their independent careers.

Moreover, she is hopeful that young researchers and more experienced investigators will together be able to unlock the mysteries of neurological disease, ultimately providing new treatments — and new hope — to children and their families.