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Genomics researcher named among handful at top of field

by Scott Brinckerhoff - January 26, 2009

Xudong Yao, an assistant professor of chemistry in the College of Liberal Arts and Sciences, is being honored by Genome Technology magazine as one of the world’s 30 top young investigators in the field of genomics and related sciences.

Yao, 43, was selected for innovative use of mass spectrometry in studying proteins associated with cystic fibrosis and cellular signal communication.

The mass spectrometer – an instrument costing more than $500,000 – uses magnets and electrical fields to reveal distinct proteins in cellular material.

His work can be seen as the next step beyond the Human Genome Project, which cataloged all the genes in the human body. One of the achievements of that project was the discovery of particular genes that contribute to certain diseases, including cancer, a disease that also figures in Yao’s work.

Protein interactions
Yao’s science is called proteomics, a combination of the terms “protein” and “genomics.” It relates to the cataloguing of proteins in human cells and the study of how they interact and the impact those interactions have on human health.

The title of a 2001 conference on proteomics, “Human Proteome Project: Genes Were Easy,” underscores the challenge being undertaken by Yao and his colleagues. If the genome consists of 40,000 genes, the proteome is far harder to quantify and understand because cells modify proteins constantly, and a typical cell may make hundreds of thousands of identifiable proteins.

It is in this arena that Yao pursues proteins that may trigger two of the world’s dreaded diseases. His success may ultimately lead to new and more effective drugs.

His postdoctoral adviser at the University of Maryland, Catherine Fenselau, explains proteomics like this: “Proteomics is the post-genomic science that examines many proteins at once to tell us how the genome’s blueprint is being implemented in cell biology. In addition to increasing our fundamental understanding of cellular function, we expect to recognize changes in proteins that provide semaphores for diseases and for responses to therapeutics. Rapid and sensitive characterization of such protein biomarkers will augment traditional medical diagnostics and pathology.”

She adds, “Professor Yao is one of the most outstanding young scientists currently contributing new methods to the new frontier of proteomics. He brings to his UConn students experience in a proteomic start-up company, experience in a mid-sized biotechnology company, [and] great energy and skill in laboratory research.”

To decipher the content and message of a single cell, Yao works at the molecular level. He inserts a tiny amount of a protein material from both healthy and diseased people into the mass spectrometry instrument, a box that includes a vacuum chamber, electrical charges, and the ability to cause the material being investigated to become a gas.

Once converted and charged, the material is weighed as part of the identification process, difficult though the concept of weighing something invisible to the naked eye may be.

Xudong Yao, assistant professor of chemistry, in his lab.
Xudong Yao, assistant professor of chemistry, in his lab. Photo by Peter Morenus

The process takes a few hours or as long as a full day; at the end, Yao studies the result in the form of a two-dimensional visual image called a mass spectrum. The process, consisting of many separate “events” in the mass spectrometry device, produces thousands of images.

Yao is being honored by Genome Technology in part for the methods he is introducing for studying large numbers of fragments of proteins called peptides. Their mass spectrometry analysis is a cornerstone of proteomics.

A Eureka moment
Asked if he has experienced what is often called a “eureka moment,” in which vexing issues suddenly become clear, Yao laughs.

“My most recent one was in early January,” he says.

“For six months, I’d been thinking about a design for a new reagent (a chemical used to introduce a reference point into a sample being analyzed). I was writing about something totally unrelated when it came to me. I believe it will work, and we will be able to patent it.”

He anticipates this type of reagent will be a valuable new tool for proteomics, especially its newest areas of study, which will include the engineering of stem cells as therapeutics for such human diseases as cystic fibrosis.

Yao collaborates with colleagues in the colleges of liberal arts and sciences and agriculture and the School of Medicine. Much of his research is funded by the Cystic Fibrosis Foundation and the American Cancer Society.

He also teaches classes in how to separate materials for analysis and the use of mass spectrometry.

“Yao’s path-breaking work in mass spectrometry is one outstanding example of how the basic research being carried out in the science laboratories of the College of Liberal Arts and Sciences yields practical benefits,” says Jeremy Teitelbaum, dean of the college.

Yao’s career includes a foray into the world of pharmaceutical companies.

He graduated from Nanjing University in China with a degree in polymer chemistry, earned a Ph.D. at the University of Maryland Baltimore County, and did postdoctoral training in mass spectrometry and proteomics. He then entered industry, working for companies in Switzerland and the U.S.

While industry had its benefits – the Swiss company had a roomful of mass spectrometers – Yao missed pure science and was pleased to find a home at UConn, where he can pursue fundamental benefits that chemistry can produce.

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