Scripps Research scientists and student garner prestigious American Chemical Society awards

Innovations in carbon-hydrogen catalysts, RNA-modifying medicines, microbiome remodelers and protein mapping technologies draw accolades from chemists’ professional association. 

September 29, 2021

LA JOLLA, CAAn array of national awards announced by the American Chemical Society honors the life-changing work of four Scripps Research principal investigators and one student from the institute’s highly ranked Skaggs Graduate School of Chemical and Biological Sciences.

The awards highlight a variety of chemistry approaches, but all have one core concept in common: they represent innovations that changed scientific thinking for the benefit of humanity.

The awards recognize advances that are addressing a form of muscular dystrophy, cancer, inflammatory diseases, atherosclerosis and more. They cover achievements in chemistry graduate education; discovery at the intersection of chemistry and biology; a field of chemistry inspired by natural processes; and catalysis, which refers to acceleration of the rates of chemical reactions through the addition of a small amount of designed catalysts not consumed by the reaction.

The awards announced Sept. 26 highlight the following Scripps Research scientists and student:

Nobel Laureate Signature Award for Graduate Education in Chemistry

Student: Alicia Angelbello, PhD

Advisor: Matthew Disney, PhD

The ACS 2022 Nobel Laureate Signature Award for Graduate Education in Chemistry recognizes exceptional students and their advisors with plaques inscribed with the signatures of Nobel laureates, with the permission of the Nobel Foundation.

This year the Nobel Signature award honors Fort Lauderdale native Alicia Angelbello, PhD, a Skaggs Graduate School student, and her advisor, chemistry Professor Matthew Disney, PhD. Their work describes 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. 

RNA acts as the middleman between DNA and proteins. 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.

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. Angelbello applied those insights to develop potential drugs for 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.

Disney says Angelbello is highly worthy of the award.

“It has been a great blessing to witness 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.”

Angelbello says the Skaggs Graduate School is a unique, hands-on program that encourages interdisciplinary, original research. She credits Disney with inspiring and challenging her to do more than she thought possible.

“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.

Angelbello joined the Skaggs Graduate School of Chemical and Biological Sciences at Scripps Research in Jupiter in 2015, and earned her PhD last year. Angelbello is now working at biotechnology company Expansion Therapeutics to improve the myotonic dystrophy 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. 

The Gabor A. Somorjai Award for Creative Research in Catalysis

Jin-Quan Yu, PhD

In order to make new molecules with new properties, chemists hunt for ways to pull apart the very stable, non-reactive carbon hydrogen bonds that make up most organic molecules, so they can then add a chemical group with other functional properties.

It’s not an easy task, but the 2022 ACS Gabor A. Somorjai Award for Creative Research in Catalysis recognizes a master in the field, Jin-Quan Yu, PhD, Bristol Myers Squibb Endowed Chair in Chemistry, and Frank and Bertha Hupp Professor of Chemistry at Scripps Research.    

Making new chemicals that will become the next generation of medications or consumer products requires new ideas and methods. When confronted with an intriguing new chemistry problem, Yu looks away from the standard substrates that are typically used by chemists. He sometimes identifies helper molecules that act as chaperones or catalysts to accomplish what might take dramatically longer otherwise. These have included metals such as palladium. His catalysts sometimes play a temporary part and then exit. His work considers the fact that many molecules are chiral. Like a left and a right hand, their asymmetric versions may have useful, different properties.

His innovative approaches have produced more than 100 new methods to functionalize carbon-hydrogen bonds. They enabled the hydroxylation and arylation of carbon-hydrogen bonds, a reaction finding applications in large-scale pharmaceuticals production. They are enabling DNA molecules to be used as a sort of bar code to facilitate the search for new medicines. They are also creating new chemical space to address previously undruggable diseases. To that end, Yu is a co-founder of the biotechnology company Vividion Therapeutics. 

After winning a MacArthur Fellowship in 2016, Yu told an interviewer that welcoming failure was a key to his success.

“It is crucial to analyze the negative result and try to extract useful information that will take you forward, even if it is a tiny step,” Yu says. “Failure and frustration are an intimate part of research.”

The Alfred Bader Award in Bioinorganic or Bioorganic Chemistry

Benjamin Cravatt, III, PhD

The Alfred Bader Award in Bioinorganic or Bioorganic Chemistry recognizes outstanding accomplishments at the interface of biology and organic or inorganic chemistry. The 2022 award goes to Benjamin Cravatt, PhD, who has developed protein-mapping technologies on a quest to find new ways to address drivers of disease which may have previously been considered “undruggable.”

Cravatt, a member of the National Academies of Sciences and Medicine, is a professor of chemistry and the Gilula Chair of Chemical Biology at Scripps Research. His work has opened up new avenues of attack against cancer, autoimmune and neurological diseases. An original thinker, he is also entrepreneurial. Cravatt is a co-founder of Vividion Therapeutics, Abide Therapeutics and ActivX Biosciences.  

“The most significant biomedical problems require creative, multidisciplinary approaches for their solution,” Cravatt says. “Our lab aims to develop chemical technologies that address fundamental challenges in human physiology and disease that are beyond the scope of contemporary methods.” 

The ACS Ronald Breslow Award for Achievement in Biomimetic Chemistry

M. Reza Ghadiri, PhD

Biomimetic chemistry draws inspiration from natural reactions to build complex molecules with potential utility as medicines, research probes or industrial functions.

The ACS 2022 Ronald Breslow Award for Achievement in Biomimetic Chemistry is awarded to Scripps Research chemistry Professor M. Reza Ghadiri, PhD, for his demonstration that directed gut microbiome remodeling can be used to fight disease.

Ghadiri’s lab incorporates biomimetic chemistry methods with other disciplines, including engineering, bioinformatics, materials science and medicine, to devise new ways of improving human health, fighting disease and understanding the origin of life.

Ghadiri has recently used biomimetic methods to discover peptides able to remodel the gut microbiome in mice to improve their cholesterol levels. The molecules his group discovered selectively destroy unhealthy gut bacteria, allowing healthy varieties to flourish. 

“Our gut microbiome has up to 1,000 different species in it. Its genetic diversity is 100 times greater than our genetic diversity. We know diet affects gut microbiome. We thought, if somehow, we can remodel the gut microbiome in mice fed the Western diet, we wondered if that would reduce cholesterol.” 

Their studies demonstrated that remodeling the microbiome with their peptides did improve the health of those fed a Western diet. They showed reduced hardening of the arteries over time, as well as reduced inflammatory markers. Ghadiri’s goal now is to develop the microbiome remodeling peptides into possible medications.  

 “We cannot live without our microbiome. It correlates with all kinds of chronic diseases, including atherosclerosis, heart disease, diabetes, inflammatory diseases, mood disorders, CNS diseases such as Parkinson’s, etcetera,” Ghadiri says. “We created a unique class of molecules that can selectively slow down undesirable bacteria, lower bad cholesterol, reduce atherosclerosis and reduce inflammation.”

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