Human Health

Alzheimer’s, Diabetes, Heart Failure, Cancer, Obesity, and Asthma

To improve human health researchers must understand disease mechanisms at a molecular level. Our technologies provide unprecedented views of how molecules interact, when they are mis-regulated, and where they are mutated during disease progression.  With this detailed information chemists can design better drugs and clinicians can provide better diagnoses. We have active funding to apply our techniques to nearly a dozen different human diseases. This work is typically done collaboratively with world-renowned scientists and physicians from across the country, e.g., UW-Madison, Mayo Clinic, U. Pennsylvania, Sanford Burnham, Princeton, UT-Southwestern, UC-San Francisco, among many others.

Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD, Carson JJ, Tonelli M, Balloon AJ, Higbee AJ, Westphall MS, Pagliarini DJ, Prolla TA, Assadi-Porter F, Roy S, Denu JM, Coon JJ. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Molecular Cell, 2012, 49 (1): 186-199.

Lera RF, Potts GK, Suzuki A, Johnson JM, Salmon ED, Coon JJ, Burkard ME. Decoding Polo-like kinase 1 signaling along the kinetochore-centromere axis. Nature Chemical Biology, 2016

Chemical Instrumentation

ETD, Dissociation, Ion/Ion Reactions, PRM, and Theory.

MS instrumentation is the gold standard technique for molecular analysis. Since 2005, our group has published over 60 research articles in the area of instrumentation. One significant achievement was the coupling of ETD to the Orbitrap mass analyzer and today hundreds of these systems are in use worldwide! Other key developments include negative ETD (NETD), parallel reaction monitoring (PRM), intelligent data acquisition, coupling of gas chromatography to the Orbitrap mass analyzer, and laser-activated ETD.

Swaney DL, McAlister GC, Coon JJ. Decision tree-driven tandem mass spectrometry for shotgun proteomics. Nature Methods, 2008, 5 (11): 959-964.

Peterson AC, Russell JD, Bailey DJ, Westphall MS, Coon JJ. Parallel reaction monitoring for high resolution and high mass accuracy quantitative, targeted proteomics. Molecular & Cellular Proteomics, 2012, 11 (11): 1475-1488.

Informatics

Molecular Identification, Quantitation, and Data Visualization.

The ability to rapidly identify, quantify, and compare molecules between samples is fundamental to gaining functional insight into biological systems. First, we develop custom instrument control code for new methodology or to acquire data tailored to specific experimental needs. Next, we develop algorithms and software tools to accelerate data analysis and the procurement of biological insight.

Wenger CD, Phanstiel DH, Lee MV, Bailey DJ, Coon JJ. COMPASS: A suite of pre- and post-search proteomics software tools for OMSSA. Proteomics, 2011, 11 (6): 1064–1074.

Bailey DJ, Rose CM, McAlister GC, Brumbaugh J, Yu P, Wenger CD, Westphall MS, Thomson JA, Coon JJ.  Instant spectral assignment for advanced decision tree-driven mass spectrometry. Proceedings of the National Academy of Sciences, 2012, 109 (22): 8411-8416.

Kwiecien NW, Bailey DJ, Rush JP Matthew, Cole JS, Ulbrich A, Hebert AS, Westphall MS, Coon JJ. High-resolution filtering for improved small molecule identification by GC-MS. Analytical Chemistry, 2015, 87 (16), 8328-8335.

Proteomic Technology

PTMs, Comparative Proteomics, Deep Sequencing, and Interaction Mapping.

We have described strategies for comprehensive analysis of numerous PTM types, including acetylation, glycosylation, methylation, and phosphorylation, among others. For comparative proteome analysis we recently developed an entirely new method of protein quantification called neutron encoding – NeuCode. This method enables whole animal labeling and is now a commercial product. At the same time we have pursued new methodology to allow deep, rapid sequencing of whole proteomes, culminating in our analysis of nearly the whole yeast proteome in one hour of MS analysis. We continue to innovate in this area and are currently working on profiling an entire human proteome on a similarly rapid time scale.

Hebert AS, Merrill AE, Bailey DJ, Still AJ, Westphall MS, Strieter ER, Pagliarini DJ, Coon JJ. Neutron-encoded mass signatures for multiplexed proteome quantification. Nature Methods, 2013, 10 (4): 332-334.  

Hebert AS, Richards AL, Bailey DJ, Ulbrich A, Coughlin EE, Westphall MS, Coon JJ. The one hour yeast proteome. Molecular & Cellular Proteomics, 2014, 13 (1): 339-347.

Metabolomic Technology 

GC-Orbitrap, Small Molecule, and Lipids.

Small molecule analysis is an emergent area of study – both in the biomedical sciences and our laboratory. Metabolites and lipids are critical biological effector molecules; however, it is increasingly appreciated that our current technological toolkit is not sufficient for their global mapping in biological systems.  We are driving technological innovations aimed to fill this gap.

Peterson AC, McAlister GC, Quarmby S, Griep-Raming J, Coon JJ. Development and characterization of a GC-enabled QLT-orbitrap for high resolution and high mass accuracy GC/MS. Analytical Chemistry, 2010, 82 (20): 8618–28.

Stefely JA, Reidenbach AG, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, Saunders J, Johnson IE, Minogue CE, Wrobel RL, Barber GE, Lee D, Li S, Kannan N, Coon JJ, Bingman CA, Pagliarini DJ. Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis. Molecular Cell, 2015, 57 (1): 83-94.

Plant, Biofuel, & Bioenergy

Symbiosis, Alternative Fuels, and Natural Products.

We have a long-standing effort to leverage our proteomic methodologies to understand the symbiosis that occurs between legumes and their nitrogen-fixing symbionts. Of the many elusive grails of agricultural biotechnology, the ability to confer nitrogen fixation into non-leguminous plants such as cereals ranks near the very top. We also work closely with UW-Madison bioenergy researchers to characterize microbial and chemical technologies and their ability to deconstruct plant lignin.

Rahimi A, Ulbrich A, Coon JJ, Stahl SS. Formic-acid-induced depolymerization of oxidized lignin to aromatics. Nature, 2014, 515: 249-252

Muthusubramanian V, Dhileepkumar J, Mireille C, Genre A, Balloon AJ, Junko M, Forshey K, Desiree den Os, Kwiecien NW, Coon JJ, Barker DJ, Ane JM. A role for the mevalonate pathway in early plant symbiotic signaling. Proceeding of the National Academy of Sciences, 2015, 112 (31): 9781-9786.

Earn your Ph.D. with us

The Coon Group is always on the lookout for new members.  Professor Coon accepts students from several UW-Madison doctoral programs including Chemistry, the Integrated Program in Biochemistry (IPiB), and Cellular & Molecular Pathology.