July 19, 2010

The Science and Art of Running a Core Facility

Steven Hall, PhD, manager of the Sandler-Moore Mass Spectrometry Core Facility at UCSF, juggles duties to help research advance more smoothly.

Once in a while, the stars – or molecules – align such that a career trajectory happens to converge neatly with advances in science and technology. Steven Hall, PhD, who manages the Sandler-Moore Mass Spectrometry (SMMS) Core Facility at UCSF, is a case in point.

As one of more than 80 core facilities at UCSF, the SMMS Core Facility makes its services available to all campus investigators, including those affiliated with the University at the Gladstone Institutes and San Francisco Veterans Affairs Medical Center. The SMMS Core Facility also serves as the mass spectrometry core for the UCSF Helen Diller Family Comprehensive Cancer Center.

The lab has five mass spectrometers, all dedicated to the science of proteomics, which entails answering biological questions by investigating the structure of proteins at the molecular level. The high cost of the instruments (one mass spectrometer can cost anywhere from $300,000 to $1 million) requires that institutions adopt a time-sharing approach to their use.

Addressing Complex Science with a Dose of Diplomacy

Hall and his staff maintain the equipment and conduct the analyses. His title is director of operations, but the words hardly do justice to the job’s complexity. Not only are the scheduling a challenge and the science complex, but the job requires a heavy dose of diplomacy as well.

“You’re interacting with any faculty who walk through the door, as well as postdocs and grad students,” Hall said. “They’re all passionate about their research, they want you to know all about it and they have all these questions they want answers to,” he said. “So myself and our staff have to be able to talk science at different levels according to individual investigators’ varying backgrounds.”

Mass Spectrometer.

Though mass spectrometry can be crucial to the success of an investigator’s work, research labs seldom need it on more than an occasional basis. Still, the facility is in consistently high demand from a wide variety of researchers, many of whom want their data yesterday.

Hall also has the occasional task of breaking disappointing news to researchers who arrive at the facility filled with hope.

Mass spectrometry, an analytical technique for determining molecular mass, isn’t new. The technique has existed since the late 1800s. However, thanks to technological advances over the last 30 years, mass spectrometry is now amenable to protein analysis. Mass spectrometers measure the molecular mass of proteins and peptides (pieces of proteins) and have many applications. For example, information regarding a protein’s structure enables scientists to determine how drugs might target the protein by fitting into its structure.

Alternatively, mass spectrometry can determine molecular structural differences between proteins isolated from the blood of a breast cancer patient and those from a healthy woman. This latter example highlights the relatively new translational research area of discovery and validation of the protein biomarkers of disease, a field in which mass spectrometry will continue to play a prominent role.

And given its potential for answering basic scientific questions about protein structure, mass spectrometry is often a path on which researchers pin their hopes.

The Art of Finesse While Maintaining Hope

That’s where the diplomacy – and education, mixed with finesse in the art of the gentle letdown, while maintaining hope – comes in.

“Mass spectrometry can answer a lot of questions, but there are also many that it can’t answer,” Hall said. “A lot of times, some of the questions investigators have can’t be answered by mass spectrometry. It might give them information that leads them down a different path, but it won’t give them the answers they’re looking for.”

In such cases, Hall finds himself in the role of educator. “Despite being a very powerful technique, many investigators have preconceived notions about the limitations of mass spectrometry, which is perfectly understandable, given that protein mass spectrometry is a constantly evolving field,” Hall said. “In these situations, it’s our job to educate them regarding the capabilities within the core facility and then, together, craft a rational experimental approach to answering their questions.”

Hall earned his PhD degree in 1989 in analytical chemistry from Loyola University of Chicago and spent six years at UCSF, first as a postdoc, and then as an assistant research chemist. In 2003, while he was working at Applied Biosystems, a manufacturer of mass spectrometers specifically designed for protein analysis, Susan Fisher, PhD, who directs UCSF’s Human Embryonic Stem Cell Program, recruited him to run the mass spectrometry core facility she was starting.

He seized the opportunity. “I’m that type of person,” Hall said. “When I see a door open, I go through it, especially when an opportunity like this falls in your lap. It was the right time in my career to return to UCSF.” Fisher, who is the faculty director of the SMMS Core Facility, is Hall’s boss.

The Lure of High-Caliber People at UCSF

Returning to UCSF after a successful sojourn in the corporate world is not uncommon at UCSF, and it’s a career path that Chancellor Susan Desmond-Hellmann, MD, MPH, is certainly familiar with. In fact, in deciding to return to UCSF, the chancellor said, one of the biggest lures was the people.

Similarly, Hall said, it was Fisher and others of her caliber who enticed him back to UCSF. He arrived as the core lab’s first official employee, and he was soon followed by Hall’s co-director, Ewa Witkowski, PhD, whom he and Fisher recruited. The facility has since grown to its current staffing level of nine scientists.

The facility’s interactions with UCSF scientists are an example of hybrid vigor at its best. One of UCSF’s strongest emphases is on biology as it relates to human disease, and the facility plays a major role in the quest to identify protein biomarkers for particular diseases. For instance, a long-term goal of such work is to identify proteins that are indicative of the earliest stages of breast cancer, prior to tumor detection.

“The thing that makes our lab really cool is that we have all these biologists who can inform us about proteins to be looked at,” said Eric Johansen, PhD, the SMMS Core Facility lab manager. “We use the resources of the UCSF biologist to inform our searches for biomarkers. We’re not letting the machines do all the work.”

Johansen, who turned to Hall as an informal mentor during graduate school, said Hall is a continuing inspiration to him. “The way he balances all the work on our plates is really impressive,” Johansen said. “His whole management approach helps with time management and getting help when you’re stuck.” The result, said Johansen, is a much more efficient advancement of research.

Photos by Elisabeth Fall