
Speeding the pace of protein sequencing will help researchers discover biomarkers that signal cancer or cancer types. Image: pierrepo/Flickr
Currently, protein sequencing is about 10,000 times slower than DNA sequencing – delaying the discovery of protein biomarkers that can help doctors catch cancer early, and that offer essential clues in how to treat it.
University of Colorado Cancer Center investigator Jay Hesselberth, PhD, assistant professor of biochemistry and molecular genetics at the University of Colorado School of Medicine, recently received a Damon Runyon-Rachleff Innovation Award to bring protein sequencing up to speed. The $450,000 award is given by the Damon Runyon Cancer Research Foundation to support “exceptionally creative thinkers with high-risk/high-reward ideas.”
DNA sequencing fundamentally changed fields ranging from chemistry, to biology, to medicine, to evolution — making protein sequencing practical could have a similar effect.
“The state of the art is mass spectrometry,” Hesselberth says, “but the problem with mass spec is that we’re rapidly hitting the speed limit of the technology – we need a different way to identify proteins, and this is one way to do it.”

Jay Hesselberth, PhD, CU Cancer Center investigator and assistant professor of biochemistry and molecular genetics at the University of Colorado School of Medicine
Drawing inspiration from DNA sequencing, Hesselberth has designed a method that can look at billions of protein segments contained in, for example, a human blood draw, all at the same time.
“In DNA sequencing, a sophisticated microscope is used to build a sequence, one block at a time, for millions of DNA templates simultaneously. In this new protein sequencing method, you pull proteins apart one block at a time, but the concepts are the same,” Hesselberth says. “It’s nothing fancy, actually – it uses existing technologies and the innovative part is combining those methods in a new way.”
The National Institutes of Health commits significant funds to finding protein biomarkers of disease. “Imagine that the NIH has funded 1,000 labs for the last five years for biomarker research using mass spectrometry,” Hesselberth says. “If protein sequencing were accelerated to the level of DNA sequencing” – as would Hesselberth’s technique – “it might take only one lab six months to do the work those 1,000 labs have done in five years.”
Currently, Hesselberth’s lab is capable of doing simple experiments, but with the concept proven, he hopes full implementation is possible within the award’s three-year window.
“I love technology development,” Hesselberth says, “I spend half my time figuring out what we can’t do and how we might do it. This is one of the few cases I have experienced in which a foundation had the foresight to say, this is at a really early stage, but wouldn’t it be amazing if it worked?. They are willing to take risks, and that’s what it takes to develop new methods.”
