Jesus Moreno

Many doctors and scientists bemoan organic chemistry courses. After all, a bad grade in this challenging subject can change a person’s career trajectory. That was true for Jesus Moreno—just not in a negative way. “I think it was one of the first Cs that I ever got,” Moreno says. “But I really loved it.”

Rather than let organic chemistry deter him, Moreno decided to master it. By the time he finished his yearlong course in the subject at the University of California San Diego, he’d switched his major from biochemistry to organic chemistry. “It really taught me how to shift my problem-solving thinking and my critical-thinking skills,” says Moreno, who is now a principal scientist and medicinal chemist at Bristol Myers Squibb (BMS).

He further honed his critical-thinking skills as a graduate student at the University of California, Los Angeles. Moreno would whip through pen-and-paper problems just as easily as he could wrangle the practicalities of a total synthesis. “He was thinking at a very detailed level and was able to solve some really tough problems,” his PhD mentor, Neil K. Garg, says.

Garg recalls how Moreno tackled the total synthesis of the plant-derived alkaloid picrinine, a complex, cage-like molecule first isolated from the leaves of the blackboard tree (Alstonia scholaris) in 1965. It’s a structure that would intimidate any organic chemist, Garg says, but Moreno “had no fear.”

Moreno distinctly remembers the Tuesday night that he and Joel M. Smith, a fellow graduate student in Garg’s group, succeeded in the first total synthesis of picrinine. Moreno worked on the project for a year and a half, and the others in the lab had been trying to make the molecule for about a year before he joined. Using thin-layer chromatography, Moreno monitored the last synthetic step, watching as the starting material cleanly changed into something else—a transformation that had previously been messy. He rushed to the nuclear magnetic resonance spectrometer to analyze the material. When he returned, he and Smith compared its spectrum with that of an authentic sample of the compound extracted from plants. They found that the spectra were identical.

“That was kind of a surreal feeling, especially because we were after that natural product for a really long time,” Moreno says. He, Smith, and Garg were exuberant. “It was like we had won the World Cup.”

Moreno says that although he enjoyed doing total synthesis, he wanted a career that was more applied than academic. “Organic chemistry is the chemistry of life, and it can be used to make lifesaving drugs. That’s the application I wanted to go after,” he says.

He remembered the fulfilling experience of collaboration and teamwork during an internship at Vertex Pharmaceuticals before he began graduate school. So rather than seek postdoctoral work, Moreno decided to look for a job in the pharmaceutical industry. In 2017, he took a job with Merck & Co., and in 2020, he moved to BMS in San Diego.

Recently, Moreno has led BMS’s chemistry efforts toward making targeted protein degraders. These molecules, like molecular glues and bifunctional degraders, bind to or otherwise target disease-related proteins and tag them for removal by the body’s trash disposal system. This strategy has become popular for tackling “undruggable” proteins—proteins that defy inhibition by small molecules.

BMS’s commercialized degraders treat blood cancers, and Moreno is working on a project that will extend this approach to a broader patient population. His other recent projects focus on developing degraders for solid tumors, such as those implicated in breast cancer, ovarian cancer, and carcinomas, which are among the most common forms of cancer.

His other big goal these days is to help retain people from underrepresented racial and ethnic groups in scientific careers. “It still kind of irks me that the representation, particularly among Black and Hispanic and Latino scientists in industry, especially in my field, is embarrassingly small,” he says.

As a proud first-generation Mexican American, Moreno tries to connect with students so his scientific journey might inspire them to seek out opportunities, such as jobs and internships in science. “I think I’ve benefited from having a really good, diverse support system,” he says. “I’m at the point in my career where I feel like I’m ready to give back.”