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Northwestern University Feinberg School of Medicine
Research

Walter and Mary E. Glass Professor of Molecular Biosciences

Neil Kelleher

Neil L. Kelleher, PhD, Walter and Mary E. Glass Professor of Molecular Biosciences, professor of chemistry and medicine, and director of the Proteomics Center of Excellence at Northwestern University, is a big picture kind of guy.

“The goal is to catalogue all of the protein molecules in all of the cells of the human body,” said Kelleher, regarding the international Human Proteome Project. “We believe that the estimated 20,300 genes in the human genome are processed into upward of a billion distinct protein molecules in a healthy person.”

Responsible for the first large-scale demonstration of top-down, or whole, protein identification at Northwestern in 2011, Kelleher’s training in high-performance mass spectrometry and enzymology began in the late ’90s. He continues to bridge the Evanston and Chicago campuses to drive technological development of high-performance mass spectrometry for biology, chemistry, and medicine. 

“Medicine is going molecular, and cancer genomes are currently demonstrating this in clinical research,” Kelleher said. “Following the arc and legacy of the Human Genome Project, the role of high-resolution molecular measurement of small molecules and proteins in the body allows for a deeper molecular-level understanding of human disease. Mass spectrometry—the core capacity of our Northwestern labs—has seen major improvements in performance, and stands ready to provide high return on investment.” 

Q&A

What are your research interests?

The Kelleher Group is focused on top-down proteomics, natural products discovery and biosynthesis, and cancer epigenetics. An underlying focus, driving the major line of research, is our continued push toward optimizing instrumentation and bioinformatic approaches to best drive unique applications of top-down analysis at Northwestern, in the areas of transplantation, HIV, and cancer research. 

How does your research advance medical science and knowledge?

We measure precisely how abnormal enzymes that drive disease states create altered proteins and metabolites in precisely-grouped patient populations.

What collaborations are you involved in? 

I collaborate with about four dozen laboratories; mostly with faculty in the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Comprehensive Transplant Center. The research consortium I've begun, the Consortium for Top-Down Proteomics, now has more than 200 members and investigators.

Why is now an opportune time to collaborate with more medical school faculty?

Dean Neilson wants to grow the research enterprise; one way to do this is through an increased competitiveness in research funding, where modern metabolomics and proteomics technology is highly enabling and valued during peer review.

How did you become interested in this research?

In my youth, I rebuilt automobile engines and became interested in scientific hardware, but always loved enzymes, too. Enzymes led me through chemical biology and enzymology, which led to an interest in how abnormal enzymes drive disease.  

How is your research funded? 

Mostly through the National Institutes of Health, but Northwestern also invested in the launch phase of the Proteomics Center of Excellence. We are now planning a second growth phase on the Chicago campus, as the need for proteomics far outstrips our current capacity.

What is the future of top-down proteomics? 

The promise of a top-down strategy is that the molecular data collected on proteins will be more closely linked to disease. Accurate identification of whole proteins (instead of small, artificially-created peptides) should lead to a sharply increased rate for the identification of high-value biomarkers and early detection of disease. Another use will be the ability to track the outcome of treatments. We are dramatically changing the strategy for understanding protein molecules at a fundamental level. It’s a slow moving revolution, and Chicago has the chance to be the world’s epicenter.  

Who has been your biggest influence? 

My career path was largely influenced by my work in the late ’90s with Fred McLafferty at Cornell University and Christopher Walsh at Harvard Medical School. My mother was also a big influence and taught me never to put limits on the height of my goals, though I did not expect to be quite so well-positioned at this point in life.