Scientist to Watch

Neil Kelleher: Thinking big then doing it

Aug 1, 2006
Jeffrey M. Perkel
<figcaption> Credit: PHOTO: JASON VARNEY | http://www.varneyphoto.comVARNEYPHOTO.COM</figcaption>
Credit: PHOTO: JASON VARNEY | http://www.varneyphoto.comVARNEYPHOTO.COM

Standing exactly five feet tall - 5'1" with his shoes on - Neil Kelleher cuts an unlikely figure on the basketball court. Yet, Craig Mizzen, a colleague and collaborator at the University of Illinois, Urbana-Champaign (UIUC), says Kelleher is "surprisingly good.... He makes up with energy what he lacks in height."

In science, Kelleher has drive and a knack for knowing when to take the shot. While at a talk given by Fred McLafferty, a Cornell mass spectrometry guru, Kelleher asked some probing questions about McLafferty's blending of Fourier transform mass spectrometry (FTMS) with electrospray ionization. Kelleher sensed promise in the technology. "He had just built the better mousetrap," he says. McLafferty, in turn, noted promise in the young Fulbright scholar who mentioned he had been interviewing for graduate school.

"I turned on the sales pitch," McLafferty recalls. In 1993 Kelleher joined McLafferty and enzymologist Tadhg Begley at Cornell, where he studied the biosynthesis of vitamin B1 and spearheaded the development of "top down" protein mass spectrometry.1

Identifying a protein in the mass spectrometer requires fragmenting the molecule for sequencing. The question, says Kelleher, is when to fragment it. In traditional "bottom-up" protein mass spectrometry, the protein is trypsinized prior to analysis. But FTMS's superior mass accuracy can distinguish larger, intact protein isoforms directly. So, Kelleher and McLafferty isolated proteins in the mass spec before fragmenting them, enabling the researchers to map posttranslational modifications - what Kelleher calls "molecular hair" - with ease. "Our flavor of mass spectrometry is really going to help signaling biologists try and figure out the complexities of their proteins," he says.

Kelleher is an avid sports aficionado, playing basketball, golf (a colleague once joked, "I never saw a guy whose golf swing is absolutely horizontal," says McLafferty), and hockey. In fact, Kelleher and his friends used to recruit students to the lab based on their skill with a puck, McLafferty says.

As a postdoc at Harvard Medical School with enzymologist Chris Walsh, Kelleher applied top-down sensibilities to antibiotic biosynthesis,2 and two years later, accepted a position at UIUC. His lab now has two main foci: natural product biosynthesis, and understanding signaling logic in the human nucleus.

On the basketball court, Kelleher is aggressive, says Mizzen, "but gentlemanly." And his drive isn't reserved for the gym, says McLafferty. "Certainly, his success at Illinois has not only been because he thinks big - but he also had the energy to do it."

Title: Associate Professor of Chemistry,
University of Illinois,

Age: 36
Representative Publications:
1. N.L. Kelleher et al., "Top down versus bottom up protein characterization by tandem high-resolution mass spectrometry," J Amer Chem Soc, 121:806-12, 1999. (Cited in 158 papers)
2. N.L. Kelleher et al., "Posttranslational heterocyclization of cysteine and serine residues in the antibiotic Microcin B17: Distributivity and directionality," Biochemistry, 38:15623-30, 1999.

Correction (posted August 4):
When originally posted, this story misattributed a quote about Kelleher's golf swing. The quote is now properly attributed to McLafferty.