Reinventing protein structure research

When chemistry professor and Union College graduate John Engen ’94 realized the equipment he needed to move forward with his hydrogendeuterium exchange mass spectrometry research on protein structure didn’t yet exist, he created the necessary tools by patching together pieces of existing laboratory equipment.

And when his research surpassed the limitations of those customized tools, he approached the biotechnology firm Waters Corporation with his idea to use liquid chromatography technology to separate protein molecules in a way that had never before been done.

Now, seven years later, that idea has come to life in the form of a unique temperature-controlled cooling instrument that measures the dynamic structure of proteins in a faster and more accurate way than ever before. This new system holds the potential to allow researchers to develop new treatments for some of the world’s most common diseases.

Biopharmaceuticals—including those used to treat patients with cancer and HIV/AIDS—are becoming increasingly common, and researchers and drug developers need a system to discover and ensure the safety and effectiveness of new medications. For years, only a few analytical chemists were able to perform the existing techniques. But Engen’s system, recently released for commercial use, gives researchers in laboratories and pharmaceutical companies access to the equipment needed to identify and learn about these proteins and their implications in medicine and disease treatment.

The Road to Research

John Engen grew up in Boulder, Colo. His father was a forensic chemist and his mother, also a Union graduate, used her master’s degree in public health at a local health department. Engen, who recalls playing with his father’s lab equipment as a child, graduated from Union College in 1994 with a degree in biology and returned the following year to complete a degree in chemistry.

He stayed in Lincoln and earned his Ph.D. in chemistry at the University of Nebraska-Lincoln, and then completed postdoctoral studies at the European Molecular Biology Laboratory in Heidelberg, Germany, and Los Alamos National Laboratory in New Mexico.

In the years since graduating from Union, Engen has become recognized as an expert in the use of mass spectrometry and hydrogen- deuterium exchange to study protein structure and dynamics. Engen first opened an independent laboratory facility at the University of New Mexico, and in 2006, he accepted a position as professor of bioanalytical chemistry at Northeastern University in Boston, where he opened the John R. Engen Laboratory. Engen also serves as Faculty Fellow in the Barnett Institute of Chemical and Biological Analysis.

In June 2012, the John R. Engen Laboratory moved into a new building in downtown Boston, designated as a Waters Center of Innovation based on the university’s decades-long partnership with the Waters Corporation.

The John R. Engen Laboratory is an analytical chemistry laboratory, focusing on measuring proteins and protein-related molecules using mass spectrometry. Using this method, the researchers weigh atoms and use the resulting calculations to learn more about the atoms’ structure and dynamics. That information helps them learn more about how proteins relate to illness and disease, including viral replication, strokes, HIV and cancer proteins.

Engen and his students and staff collaborate with local medical schools, cancer institutes, and pharmaceutical and biotechnology firms to research how molecules bind to targets within patients’ bodies. It was in one such recent collaboration with the Waters Corporation that the Engen team helped create and commercialize the HD Exchange nanoACQUITY System.

This is the first commercial system that enables companies to measure proteins for therapies to treat individuals with HIV/AIDS and other diseases, rather than relying on a few researchers to provide the data. “The fastest growing sector of the pharmaceutical industry is proteins, and more companies need ways to measure the proteins to create these needed compounds and make sure their products are being manufactured correctly,” explained Engen. For example, Engen’s system is currently being used in Japan to check the insulin supply and ensure the product sold to patients conforms to the exact specifications necessary to treat those who need insulin injections.

Engen is currently on sabbatical to focus on his research. “I love working with proteins because of the implications,” he said. “Many proteins are related to diseases, and we need to be able to understand those relationships and strengthen our techniques for measuring and researching those proteins so we can better understand what’s happening in our cells and bodies. The better we understand these proteins, the better our chances to understand and do something about the diseases to which they’re related.”

From Student to Professor

Being a professor of chemistry gives Engen a chance to select top-notch chemistry students to work alongside him in his laboratory. “We have access to some of the most promising students in the field,” he says. “We bring them into our lab to give them real-world experience in a research laboratory that will make them better researchers and scientists.”

Along with undergraduate students, the John R. Engen Laboratory also selects postgraduate and Ph.D. students to work alongside their skilled senior scientists. Engen explains, “Being in our lab gives students experience in this type of setting, and at the end of their time here, they’re accomplished and able to go wherever they want to continue their education.”

Since 2006, Engen has helped more than 12 graduate students complete their degrees, and his laboratory has hosted more than 40 students and staff scientists. “I like the interaction I have with students,” says Engen. “I like to keep track of them and help them be successful. That’s the main purpose of working with a university.” Some of the classes Engen teaches have upwards of 300 students, but Engen doesn’t let that distract him from his goal to inspire individual students. “One big thing I learned at Union College is that small is good,” he says. “I spent most of my time in Jorgensen Hall, and I interacted with the same few professors every day. Our class sizes were small, and having that one-on-one time was great. It was easy to get personalized attention, and I want to bring that with me into every class I teach.”

That teacher-student relationship is one way Dr. Engen has brought a little bit of Union with him to Northeastern. “I care about my students just like my professors cared and still care about me,” he says. “My professors have been such a positive motivator in my life. Now, I take that same approach with my students. I’m happy to help turn these kids into something great, just as my professors were happy to take on that role with me.”

Even now Engen feels the support he had as an undergrad at Union. Dr. David Nowack, one of his former professors, recently contacted Engen and plans to visit his lab to see his research. Engen says, “It feels good to know my professors still care about what I’m doing and are proud that I’ve been so successful,” he says. While he’s become a celebrated researcher and professor in his own right, Engen still takes an active role in strengthening the science program at his alma mater. In 2002, he founded the John R. Engen Award in the Chemical Sciences scholarship. The cash prize is awarded each year to the junior or senior chemistry major at Union College who shows interest and promise in instrumental analysis.

Engen explains that the award is meant to inspire greatness in future researchers. “Chemistry is a hard major and students pursuing it have to take hard classes,” he says. “I know firsthand as a researcher and a professor how important it is to have scientists who are skilled at measurements and analysis. I want my scholarship to reward students in that field for their hard work, and to encourage them to keep pursuing that specialty.”

The Promising Future of Science Education at Union College

Union is also committed to helping students achieve success in the sciences. In April 2012, the college broke ground for a new two-story, 55,000 square foot science and mathematics complex to replace the aging Jorgensen Hall and revitalize the science and math programs. The building will be located in what is now a parking area on the north side of campus between Rees Hall, Larson Lifestyle Center and the Don Love Building, and is slated to be completed end of 2013. The new complex will feature state-of-the-art technology in 10 laboratories, four lecture rooms, three classrooms (including a 126-seat amphitheatre), seven research labs and three seminar rooms, and multi-use spaces for collaboration and interactive learning.

Like many math and science graduates from Union, Dr. John Engen is excited about the possibilities this new facility presents. “For students to be competitive in the sciences of our time, it is essential for them to have modern facilities,” he says. “The teaching, research and general instruction quality will be vastly improved with modern space. Unquestionably this building will have a long lasting impact on the future of all Union College students who pass through it. I am very happy to see the new building take shape and be put to use.”