Assistant Professor of Chemistry
Ph.D., University of Georgia
We are interested in High resolution mass spectrometry studies of protein post-translational modification.
Protein post-translational modification underlies most biological processes. Moreover, the dysregulation of protein modification plays a causative role in a number of disease states, especially the neurodegenerative diseases. Our laboratory studies protein modifications that occur during neurodegeneration, with focus on ALS, and tries to understand the role of modification in disease progression. We are also studying the role of protein modification in the process of memory, which can involve modifications as subtle as conformational change. We use high resolution, Fourier Transform Mass Spectrometry (FTMS), and are equipped for both electrospray and MALDI ionization, including MALDI mass spectral imaging of tissues.
Sample of Recent Publications
“The Azotobacter vinelandii NifEN Complex Contains Two Identical [4Fe-4S] Clusters,” P. J. Goodwin, J. N. Agar, J. T. Roll, G. P. Roberts, M. K. Johnson, and D. R. Dean, Biochemistry 37, 10420-10428 (1998).
“Activation of Iron and Sulfur for Nitrogenase Metallocluster Formation,” D. R. Dean, J. Christianson, P. Yuvaniyama, L. Zheng, V. Cash, J. Agar, M. K. Johnson, and D. H. Flint, Curr. Plant Sci. Biotechnol. Agric. 31, 27-31 (1998).
“Modular Organization and Identification of a Mononuclear Iron‑Binding Site Within the NifU Protein,” J. N. Agar, P. Yuvaniyama, R. F. Jack, V. L. Cash, A. D. Smith, D. R. Dean and M. K. Johnson, J. Biol. Inorg. Chem. 5, 167‑177 (2000).
“Studies on the Mechanism for the Activation of Iron and Sulfur for Formation of the Nitrogenase Metal Centers," D. R. Dean, P. Yuvaniyama, J. N. Agar, and M. K. Johnson, Nitrogen Fixation: From Molecules to Crop Productivity. Current Plant Science and Biotechnology in Agriculture 38, 37‑39 (2000).
“NifS-directed Assembly of a Transient [2Fe-2S] Cluster in the NifU Protein,” P. Yuvaniyama, J. N. Agar, V. L. Cash., M. K. Johnson, and D. R. Dean, Proc. Natl. Acad. Sci. USA 97, 599-604 (2000).
“Role of the IscU Protein in Iron-Sulfur Cluster Biosynthesis: IscS Mediated Assembly of a [Fe_2 S_2 ] Cluster in IscU,” J. N. Agar, L. Zheng, V. L. Cash, D. R. Dean, and M. K. Johnson, J. Am. Chem. Soc. 122, 2136‑2137 (2000).
“IscU as a Scaffold for Iron‑Sulfur Cluster Biosynthesis: Sequential Assembly of [2Fe‑2S] and [4Fe‑4S] Clusters in IscU,” J. N. Agar, C. Krebs, J. Frazzon, B. H. Huynh, D. R. Dean, and M. K. Johnson, Biochemistry (Accelerated Publication) 39, 7856‑7862 (2000).
“Characterization of the NifU and NifS Fe-S cluster formation proteins essential for viability in Helicobacter pylori,” J. W. Olson, J. N. Agar, M. K. Johnson, and R. Maier, Biochemistry 39, 16213-16219 (2000).
“Biological Iron-Sulfur Cluster Assembly,” P. Yuvaniyama, J. N. Agar, M. K. Johnson, and D. R. Dean, Archives of Microbiology (2001).
“Sulfur Transfer from IscS to IscU: The First Step in Iron-Sulfur Cluster Biosynthesis,” A. D. Smith, J. N. Agar, K. A. Johnson, J. Frazzon, I. J. Amster, D. R. Dean, and M. K. Johnson, J. Am. Chem. Soc. 123, 11103-11104 (2001).
“IscA, an Alternate Scaffold for Fe-S cluster biosynthesis,” C. Krebs, J. N. Agar, J. Frazzon, B. H. Huynh, D. R. Dean, and M. K. Johnson, Biochemistry, 40, 11069-14080 (2001).
“Mutations in COX10 Result in a Defect in Mitochondrial Heme A Biosynthesis and Account for Multiple, Early Onset Clinical Phenotypes Associated With Isolated COX Deficiency,”Antonicka H., Leary S. C., Guercin G, Agar J. N., Horvath R., Kennaway N. G., Harding, C. O., Jaksch M., Shoubridge E. A., Human Molecular Genetics, 12, 2693-2702 (2003).
“Relevance of oxidative injury in the pathogenesis of motor neuron diseases” J. N. Agar, H. D. Durham, Amyotroph Lateral. Scler. Other Motor Neuron Disord. 4, 232-42 (2003).
“Biological Iron-Sulfur Cluster Assembly” J. N. Agar, D. R., Dean, M. K. Johnson, in Biochemistry and Physiology of Anaerobic Bacteria, L. G. Ljungdahl, ed., Springer-Verlag, 46-66 (2003).
"Overexpression of Metallothionein Protects Cultured Motor Neurons Against Oxidative Stress, but not Mutant Cu/Zn-Superoxide Dismutase Toxicity,” D. M. Taylor, S. Minotti, J. N. Agar, H. D. Durham, Neurotoxicology, 25, 779-792 (2004).
“Focal Dysfunction of the Proteasome: A Pathogenic Factor in a Mouse Model of Amyotrophic Lateral Sclerosis,” E. M. Kabashi and J. N. Agar (co-first author), D. M. Taylor, S. Minotti, H. D. Durham, Journal of Neurochemistry, 89, 1325-1335 (2004).
“Proteasome Activity or Expression is Not Altered by Activation of Heat Shock Transcription Factor HSF1 in Cultured Fibroblast and Myoblasts.” D. M. Taylor, E. Kabashi, J. N. Agar, S. Minnoti, H. D. Durham., Cell Stress and Chaperones, 10, 230-41 (2005).
“NifS-mediated Assembly of [4Fe-4S] Clusters in the N-terminal and C-terminal Domains of the NifU Scaffold Protein,” A. D. Smith, G. L. Jameson, P. C. Dos Santos, J. N. Agar, S. Naik, C. Krebs, J. Frazzon, D. R. Dean, B. H. Huynh, M. K. Johnson, Biochemistry, 44, 12955-69 (2005).
“Tryptophan 32 Potentiates Aggregation and Cytotoxicity of a Copper/Zinc Superoxide Dismutase Mutant Associated with Familial Amyotrophic Lateral Sclerosis.” D. M. Taylor, B. F. Gibbs, E. Kabashi, S. Minotti, H. D. Durham, J. N. Agar, The Journal of Biological Chemistry, 282, 16329-16335.
Motor Neuron Disease” H. D. Durham, E. Kabashi, D. M. Taylor, J. N. Agar, in The Proteasome in Neurodegeneration, L. Stefanis and J. N. Keller ed. Springer US, 247-264 (2007).
“Matrix Solution Fixation: a Histology Compatible Tissue Preparation for MALDI Mass Spectrometry Imaging.” N. Y. R. Agar, H. W. Yang, R. S. Carroll, P. M. Black, J. N. Agar, Analytical Chemistry, 79, 7416-7423.
"Fitting Neurological Protein Aggregation Kinetic Data via a 2-Step, Minimal “Ockham’s Razor” Model: the Finke-Watzky Mechanism of Nucleation Followed by Autocatalytic Surface Growth" A. Morris, M. Watzky, J. N. Agar, R. Finke, Biochemistry, 47 (8), 2413-2427 (2008).
"Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis." Kabashi E., J.N. Agar, Minotti Sl, Durham H.D. J. Neurochem. E.Pub. Apr 1 2008.
“Protein Aggregation and Protein Instability Govern Familial ALS Patient Survival.” Q. Wang, J. L. Johnson, N. Y. R. Agar, J. N. Agar. PLoS Biology. 6 (7) e170 (2008).
“A Hierarchical Algorithm for Calculating the Entire Isotopic Fine Structures of Molecules” L. Li, J. N. Agar, P. Hong, J. Amer. Soc. Mass. Spectrom. In Press, http://dx.doi.org/10.1016/j.jasms.2008.08.008 (2008).
“Sensitive and Specific Identification of Proteins from 8 to 669 kDa using Top-Down Mass Spectrometry” M. Karabacak, L. Li., A. Tiwari., L. J. Hayward., H. Pengyu, J. N. Agar, Mol. Cell. Prot. Dec 15 2008.
“A Common Property of ALS-Associated Variants: Destabilization of the SOD1 Electrostatic Loop” K. S. Molnar, N. M. Karabacak, J. L. Johnson, Q. Wang, A. Tiwari, L. J. Hayward, S. J. Coales, Y. Hamuro, J. N. Agar. The Journal of Biological Chemistry, accepted June 27 2009.
Comprehensive assignment of energy-dependent protein fragmentation reveals dissociation via three distinct fragmentation pathways J. S. Cobb, M. L. Easterling, and J. N. Agar. Published Online Feb 2010 J. Amer. Soc. Mass. Spectrom.
Agar, N. Y., Malcolm, J. G., Mohan, V., Yang, H. W., Johnson, M. D., Tannenbaum, A., J. N. Agar, Black, P. M.. "Imaging of meningioma progression by matrix-assisted laser desorption ionization time-of-flight mass spectrometry." Anal Chem 82. 7 (2010): 2621-5.
“Transformative effects of higher magnetic field in Fourier transform ion cyclotron mass spectrometry” N. M. Karabacak, M. L. Easterling, J. N. Agar. J. Amer. Soc. Mass. Spectrom. (Online April 2010).
“Tissue preparation for the in situ MALDI MS imaging of proteins, lipids, and small molecules at cellular resolution.” N. Y. R. Agar, J. M. Kowalski, P. J. Kowalski, J. H. Wong, and J. N. Agar in Mass Spectrometric Imaging. History, Fundamentals and Protocols. Methods in Molecular Biology, Humana Press, Inc. Totowa, New Jersey (Sept 2010).