Scientists who follow the RNA mutation strategy

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Scientists who follow the RNA mutation strategy

JUPITER, FL – The American Chemical Society announced that its prestigious 2022 Nobel Laureate Signature Award for Graduate Education in Chemistry honors a student from the Skaggs Graduate School of Chemical and Biological Sciences at Scripps Research and her faculty advisor, for their pioneering work developing RNA-targeting medications for genetic diseases, including a form of muscular dystrophy.

The Nobel Signature award recognizes exceptional students and their mentors with plaques inscribed with the signatures of Nobel laureates, with the permission of the Nobel Foundation.

“It has been a great blessing to witness to the growth of students in the lab. That growth, and the science they generate, is an educator’s legacy,” Disney says. “Ali is one of the most tenacious, smart and level-headed people I have ever had the privilege to work with. Those qualities will enable her to accomplish great things for the families struggling with these incurable diseases, and make the world a better place.”

Disney praised Angelbello’s intelligence, creativity and diligence as making her highly worthy of the award.

Story Highlights

  • Credit: Courtesy Scripps Research

  • Fort Lauderdale native Alicia Angelbello, PhD, spent five years studying and performing research in the lab of chemistry Professor Matthew Disney, PhD. During that time, she published key papers describing how toxic RNA involved in a type of adult-onset muscular dystrophy could be targeted and destroyed with potential drugs that could be taken as a pill. 

Angelbello says the Skaggs Graduate School was a unique program that allowed for hands-on, interdisciplinary research, and Disney was an inspiring and challenging advisor.

“I loved working with Matt Disney during my time at Scripps Research’s Skaggs Graduate School. He sets an example of working hard and being passionate about the science that we do,” Angelbello says. “He was always pushing us to learn new techniques and try new things.”

Disney first set out to find ways to attach small molecular probes to RNA 15 years ago, at a time when most scientists thought RNA could not be a drug target, due to its form, movement and other properties. RNA acts as the middleman between DNA and proteins, reading and transcribing genes, and assembling amino acids into the stuff of life. Disney’s lab has developed technologies to identify druggable structures on RNA molecules known to cause disease. Further, he built a rational approach to design compounds to grab those druggable structures, and deliver therapeutic molecules. Disney is the founder of a company based in Boston, MA and Jupiter, FL that is moving these potential therapies toward the clinic, Expansion Therapeutics. Following her graduation last year, Angelbello joined the company as a scientist on their biology team.

For her thesis project, Angelbello harnessed Disney’s inventions to help create compounds that target and destroy RNA involved in myotonic dystrophy type 1. The illness affects the ability to relax contracted muscles, and impacts about 200,000 people in the United States. It’s caused by long strings of a toxic RNA repeats. The more repeats, the more severe the disease. Angelbello and Disney’s compounds destroy the toxic genetic repeats in RNA. One of the compounds self-assembles within cells to improve potency — essentially the toxic RNA makes its own treatment, Disney says. Angelbello is now working to improve the compounds’ drug-like properties so that they could one day gain FDA approval, and possibly become among the first RNA-targeting oral medications.

 “I think there is huge potential for creating therapeutics that target these RNA mediated diseases,” Angelbello says. “Now it’s just a matter of developing and optimizing small molecule therapies that can be drugs for these patients. They payoff could be immense, because there are no treatments for these diseases, and they affect many people.” Two other current Scripps Research faculty have been honored with the ACS Nobel Signature award since it was created in 1980, including Peter Schultz, PhD, the President and CEO of Scripps Research, for doctoral work with his advisor, CalTech chemist Peter Dervan, PhD, and chemistry Professor Phil Baran, PhD, for his doctoral work with synthetic chemist K.C. Nicolaou. This year’s awardees will be honored at a ceremony in San Diego on March 22.

“Ali Angelbello is helping drive our small molecule programs in Myotonic Dystrophy Type 1, Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia. She also emulates our founder Matt Disney’s example in mentoring and inspiring junior scientists,” Skerlj says. “She’s smart, tenacious, productive and a great team player. We are proud to have Ali on the Expansion team and congratulate her and Matt for this well-deserved recognition.” ###

The CEO of Expansion Therapeutics, Renato Skerlj, PhD, congratulated Disney and Angelbello on the award. Angelbello grew up in Fort Lauderdale and attended St. Thomas Aquinas High School there. Before joining the Skaggs Graduate School of Chemical and Biological Sciences at Scripps Research in Jupiter in 2015, as an undergraduate, she studied chemistry at Villanova University, in Villanova, PA.