Molecules in Motion: A Profile of Ryan Shenvi

By Madeline McCurry-Schmidt

Remember that classic, grade-school image of molecule? The one with Styrofoam balls stuck to wooden dowels? It’s not quite right.

In real life, chemists see molecules as constantly moving structures. Each atom is capable of breaking its bonds and changing how the molecule functions.

“Reading a synthetic chemistry paper is almost like watching ballet in freeze frame,” said Ryan Shenvi, assistant professor at The Scripps Research Institute (TSRI). “Choreography is a term that’s actually used in synthetic chemistry, and it refers to the ordering of chemical reactions in a synthetic sequence.”

In his laboratory at TSRI, Shenvi focuses on creating new choreography. By inventing new chemical reactions and new molecules, Shenvi hopes to help make new classes of drugs to treat disease.

A Creative Chemist

Shenvi was raised in Wilmington, Delaware, home of the DuPont Corporation, surrounded by chemistry. Though his father—and 11 other family members—are chemists, Shenvi grew up thinking chemistry was “boring” and leaned toward art and music instead. But when he took an organic chemistry course during his sophomore year at Pennsylvania State University, he started seeing molecules and their reactions as a kind of visual art.

“I realized the beauty of it,” Shenvi said.

In 2003, Shenvi joined TSRI as a graduate student in the laboratory of chemist Phil Baran. Shenvi worked with Baran on two major projects, including the synthesis of a complex steroid called cortistatin A, which has shown promise for treating cancer and other conditions.

“I probably didn’t get a realistic perspective into what it’s like to start an academic lab, only because he [Baran] was so immediately successful,” said Shenvi. “But being part of his success was really inspiring.”

Shenvi described his graduate student experience as “incredible” and said the faculty at TSRI were especially strong. “The chemistry department here is one of the best—if not the best—in the country,” Shenvi said.

After completing a postdoctoral fellowship in the laboratory of Nobel laureate E.J. Corey at Harvard University in 2010, Shenvi had the opportunity to start his own lab at TSRI. At the same time, he was starting a family with his wife, Edna. Today he and Edna, an MD involved in medical informatics research with UC San Diego, have three kids: twin three-year-olds and a one-year-old.

Back in the lab, Shenvi and his colleagues were tackling tough problems in the field. In 2013, the team succeeded in extending chemistry into new territory with a reaction that many had thought impossible.

For years, chemists have used a reaction called the SN2 to create and modify organic molecules. The SN2 reaction is an incredibly useful tool for creating new drugs, but most chemists believed it wasn’t possible to create certain compounds that way.

Shenvi and his team proved them wrong. Using a special acid catalyst to detach a group of atoms, called a functional group, from a central carbon atom, the scientists showed that an unusual nitrogen-containing molecule would add another functional group to the other side of the atom.

Shenvi likened it to turning an umbrella inside out; the new reaction forces a molecule to become inverted, giving it a new shape with new chemical properties. This technique, which earned Shenvi a National Science Foundation Career Award, could allow chemists to develop new drugs.

Next Stop: Sea Sponges?

Shenvi is especially interested in finding treatments for tropical diseases such as malaria and Chagas disease, which have not be pursued by many pharmaceutical companies. “I think it’s an area where, in terms of addressing a medical need with chemistry, we can potentially make an important contribution,” he said.

To find new molecules for potential drugs, Shenvi and his team are taking a closer look at the organisms around us.

“If you look at all the drugs that are sold— sold by pharmaceutical companies, prescribed by doctors, sold in your drug store—the vast majority of them come from living organisms,” Shenvi said.

While penicillin is one of the most famous examples of a medicine from the natural world (mold), Shenvi believes the next class of life-saving drugs could come from sea sponges and odd, blobby sea creatures called tunicates.

Scientists first took an interest in sea sponges and tunicates because the organisms excrete molecules that prevent “biofouling.” Biofouling is the term for when an object, like a buoy, is colonized by sea life like barnacles and mussels. Through some mysterious quirk of evolution, some molecules that prevent biofouling also kill the parasite that causes malaria.

“It’s a little weird because sponges don’t get malaria—there are no mosquitos at the bottom of the ocean,” he said. The activity was unexpected, but Shenvi knew one thing: if sponges could make these molecules, he could synthesize them in the lab. Synthesizing the molecules could also stop people from trawling for the ecologically fragile sponges.

“Our work could enable mass production of these compounds, but like everything else, the proof is in the pudding, and we’ve only made a little pudding so far,” he said.

While these small molecules themselves have only a slim chance of becoming new drugs, researching the chemical interactions between them and the malaria parasite could show scientists how they might use similar compounds to stop malaria and other diseases, such as cancer.

The creativity needed to solve such problems is why he fell in love with chemistry in the first place. “Coming up with that choreography is very exciting,” Shenvi said.

Send comments to: press[at]scripps.edu