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From Signal Transduction to Cystic Fibrosis

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  • Title: Assistant Professor, University of Connecticut
  • Education: PhD, University of Maryland, 2000
  • Recommended by: Catherine Fenselau

It's not every scientist who can successfully juggle basic research with clinical studies, but Xudong Yao has found a way. His lab at the University of Connecticut has an ongoing collaboration with the Cystic Fibrosis Foundation, but he also maintains an emphasis on the more fundamental side with a focus on phosphorylation and understanding signal transduction.

Yao came to the US in 1995 after earning his bachelor's and master's degrees at Nanjing University in China. He completed a PhD in 2000 at the University of Maryland, and stayed at the school for another few years to carry out a postdoc with Catherine Fenselau. The Fenselau lab has a long tradition of combining "chemistry strategies with mass spectrometry to study biomedical problems," Yao says. His goal there was to work on approaches that would allow scientists to perform "selective analyses of certain numbers of protein targets in order," he says, noting that as proteomics advances, people are looking for a greater level of control over how peptides or proteins are targeted for analysis.

But Yao's path to UConn wasn't a direct one. He "took a detour," he says — he headed to industry for a short time, working first at GeneProt and then at Millennium Pharmaceuticals. While he's glad to be back in academia, his time in industry was a stroke of luck: through GeneProt, he met Diana Wetmore, now a leader at the Cystic Fibrosis Foundation and Yao's connection for establishing a partnership with the group.

Through the collaboration with the foundation, Yao's lab uses "a mass spec assay to monitor the plasma membrane expression" of CFTR, the critical gene linked to cystic fibrosis. His time in industry has given Yao an awareness of the importance of getting great tools out to potential users, and he hopes that his work with the assay for CFTR will be one example of this. "Hopefully this can be expanded to related proteins," he says, "so that it can be applied to personalized medicine."

On the basic research side, Yao and his team are busy trying to get at the sequence of phosphopeptides that govern regulation of signal transduction. "We try to use a chemical method in addition to gas-phase reaction [to enable] ultra-high specificity and a very high yield of certain ions," he says. "By doing this we can increase the sensitivity by tens of times."

Looking ahead

Going forward, Yao says he hopes to "continue to strengthen our relationship with the Cystic Fibrosis Foundation." That involves applying new mass spec methods "to help find a cure of this disease," he adds. Meantime, he will continue the focus on basic research as well, trying to figure out "how to increase the intrinsic sensitivity and selectivity of the analysis of those molecules," he says. He also expects that his lab will move more in the direction of what he calls "pathway phosphoproteomics." This concept could eventually help in the clinical realm as well, he says, noting that many proteomic biomarkers tend to be difficult cases for mass spec analysis.

Publications of note

Last year, Yao co-authored a paper entitled "Oxygen isotopic substitution of peptidyl phosphates for modification-specific mass spectrometry," which was published in Analytical Chemistry. The paper reports "the first method of isotopic substitution of a nonbridging oxygen atom in pre-existing phosphates on peptides," which, according to the authors, solves "a long-standing, challenging issue in the sample preparation of phosphopeptides," the abstract states.

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