The team, which includes 15 members ranging from undergraduates to postdoctoral researchers to tenured faculty, designs tools based on the reactivity of these sulfur molecules to study what happens to them in biological systems. This work ranges from designing compounds to neutralize, remove, detect or even generate the molecules in a biosystem.

One project, for instance, involves creating a chemical sensor to detect specific sulfur-containing molecules called sulfane sulfurs in the presence of biological fluids. Recent studies have shown that decreased levels of sulfane sulfurs in blood plasma may be a clue to someone developing cardiovascular disease in the future. The disease has been the leading cause of death in the United States since the 1950s.

The sensors are designed to bind with sulfane sulfur molecules and emit a fluorescence or glow so the sulfane sulfur can be visualized and tracked within cells and tissues. The idea is to develop a non-invasive way to map sulfane sulfur distribution in different cellular components as cardiovascular disease develops, said Meg Shieh, a third-year Ph.D. student who is playing a leading role in the work.

“This work will help us better understand the cardioprotective effects of sulfane sulfurs in cardiovascular disease,” said Shieh, who joined the lab in 2022.  “Hopefully this knowledge will improve our ability to detect cardiovascular disease for earlier treatments and may help identify more effective treatments, thus lowering the mortality rate of cardiovascular disease.”

Another project involves the creation of what are known as sulfur donor compounds. These chemical tools allow scientists to precisely control the release of certain sulfur molecules in living systems. In a recent study published in Nature Communications, the lab reported a novel compound that can promote cellular sulfane sulfur production. The donor compound, named TTS, and others like it may eventually be used to increase sulfane sulfur levels in patients.

A rigorous production process

Developing these chemical compounds is no easy feat. In fact, it’s incredibly tricky and rigorous. Some compounds can take days, weeks and even months to synthesize. Hydrogen sulfide, for instance, is notoriously difficult to work with, Xian said.

The process involves trial and error as the team researches similar compounds and then experiments with different mixtures and conditions to develop a compound that does what the researchers intend.

At any point, lab members, like third-year Ph.D. student Stephen Lindahl, say they often need to adapt their methods based on the results they are seeing and sometimes look for new uses or unexpected properties of the compounds they develop.

Based in Brown’s Geology-Chemistry Research Building, members of the Xian lab take advantage of a range of technologies and equipment to prepare and validate the compounds. The scientists routinely use fluorescence spectrophotometers, microplate readers, fluorescence microscopes and gas microsensors in their research.

The hard work pays off for the group. Labs both within Brown and outside of it have taken note of the range of the Xian lab’s chemical tools and approached members for research collaborations. Xian estimates the group has collaborated with and shipped out their compounds to more than 40 groups around the world. They have received patents for some of the compounds, which are now commercially available to researchers.

“Collaborations are very important for us,” Xian said. “Our research focuses on inventing novel chemicals that can be used for biomedical research. Our collaborators can apply our chemicals on all kinds of disease models, so the more people are using our chemicals, the stronger the impact.”

An autonomous but collaborative team

One of the lab’s key attributes, according to the team, is its support for members to pursue their own projects and ideas within the group. In fact, Brown sophomore Naya Melvani said it was one of the main reasons she joined the lab last year and is continuing this fall.

“If you have an idea for a project or if you want to take a project in a certain direction, you are really given the opportunity to do that,” Melvani said. “I work under a postdoc, but there’s always opportunities for me to take little angles of what she’s doing and explore other avenues. That freedom is really valuable, and getting that flexibility and autonomy as an undergrad is rare and really special.”

Melvani enjoys seeing how much lab members support each other, she said. One member might synthesize a compound that is then used by another team member for further experiments. And members often teach each other how to better make use of the lab’s equipment, sharing knowledge about the specific techniques that come with them.

“It really maximizes everyone’s different backgrounds and what we can do and applies them to the mission of the lab,” Melvani said. “It's really nice to see that interconnectedness.”