|
359 Chemistry Research Laboratory Ph: (304) 293 – 0175 Fax: (304) 293 – 4904 Email: justin.legleiter@mail.wvu.edu |
Personal or Group website:
http://legleiterlab.wvu.edu
Professional Preparation:
2000 B.S. (ACS certified) in Chemistry, Murray State University, Murray, KY
2005 Ph.D. in Chemistry, Carnegie Mellon University, Pittsburgh, PA
2005-2008 Postdoctoral Fellow, Gladstone Institute of Neurological Disease, The J. David Gladstone Institutes, Department of Neurology, University of California, San Francisco
Research Interests:
The long term goal of our research program is to understand disease related alterations of basic nanoscale physicochemical properties of cells, organelles, and membranes. Our current focus is elucidating the nanoscale molecular mechanisms that underlie neurodegenerative disorders associated with protein misfolding and aggregation, focusing on Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD), with a particular interest in the potential role cellular surfaces, such as lipid membranes and organelles, may play in these events. To accomplish this goal, we use a wide array of biochemical and biophysical techniques, with atomic force microscopy (AFM) as our primary tool. We are also actively involved in further developing AFM techniques that will allow us to directly study the structural and physical properties of biological surfaces with nanoscale resolution. Such techniques include methods to reconstruct tip-sample forces during tapping mode imaging in liquid environments.
Recent Publications:
1. Legleiter, J., J. D. Fryer, D. M. Holtzman, & T. Kowalewski. The modulating effect of mechanical changes in lipid bilayers caused by apoE-containing lipoproteins on Aβ induced membrane disruption. ACS Chemical Neuroscience. (2011) IN PRESS.
2. Yates, E. A., E. M. Cucco, & J. Legleiter. Point Mutations in Aβ Induce Polymorphic Aggregates at Liquid/Solid Interfaces. ACS Chemical Neuroscience. (2011) 2, 294-307.
3. Pifer, P.M., E.A. Yates, & J. Legleiter. Point mutations in Aβ result in the formation of distinct polymorphic aggregates in the presence of lipid bilayers. PLoS ONE. (2011) 6, e16248.
4. Burke, K.A., J. Godbey, & J. Legleiter. Assessing mutant huntingtin fragment and polyglutamine aggregation by atomic force microscopy. Methods. (2011) 53, 275-284.
5. Lotz, G.P., J. Legleiter, R. Aron, E.J. Mitchell, S.-Y. Huang, C. Ng, C. Glabe, L.M. Thompson, & P.J. Muchowski. Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. J. Biol. Chem. (2010) 285, 38183-38193.
6. Abraham, A., E. Mihaliuk, B. Kumar, J. Legleiter, & T. Gullion. Solid-State NMR study of Cysteine on Gold Nanoparticles. J. Phys. Chem. C (2010) 114, 18109-18114.
7. Legleiter, J., E. Mitchell, G.P. Lotz, E. Sapp, C. Ng, M. DiFiglia, L.M. Thompson, & P.J. Muchowski. Mutant Huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo. J. Biol. Chem. (2010) 285, 14777-14790.
8. Kumar, B., P.M. Pifer, A. Giovengo, & J. Legleiter. The effect of set point ratio and surface Young’s modulus on maximum tapping forces in fluid tapping mode atomic force microscopy. J. Appl. Phys. (2010) 107, 044508.
9. Sathasivam, K., A. Lane, J. Legleiter, A. Warley, B. Woodman, S. Finkbeiner, P. Paganetti, P.J. Muchowski, S. Wilson, & G.P. Bates. Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington’s disease. Hum. Mol. Genet. (2010) 19, 65-78.
10. Legleiter, J., G.P. Lotz, J. Miller, J. Ko, C. Ng, G. L. Williams, S. Finkbeiner, P. H. Patterson, & P.J. Muchowski. Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment. J. Biol. Chem (2009) 284, 21647-21658.
11. Legleiter, J. The effect of drive frequency and set-point amplitude on tapping forces in atomic force microscopy: simulation and experiment. Nanotechnology. (2009) 20, 245703.
12. Cheng, J.S., D.B. Dubal, D.H. Kim, J. Legleiter , I.H. Cheng, G.Q. Yu, I. Tesseur, T. Wyss-Coray, P. Bonaldo, & L. Mucke. Collagen VI protects neurons against amyloid-β toxicity. Nat. Neuroscience. (2009) 12, 119-121.
13. Cheng, I. H., K. Scearce-Levie, J. Legleiter, J. J. Palop, H. Gerstein, N. Bien-Ly, J. Puolivali, S. Lesne, K. H. Ashe, P. Muchowski, & L. Mucke. Enhancing the Fibrillization and Deposition of the Amyloid-β Peptide Reduces Its Negative Impact on Behavior and Synaptic Activity-Dependent Proteins. J. Biol. Chem. (2007) 282, 23818-23828.
14. Ehrnhoefer, D. E., M. Duennwald, P. Markovic, J. L. Wacker, S. Engemann, M. Roark, J. Legleiter, J. L. Marsh, L. M. Thompson, S. Lindquist, P. J. Muchowski, and E. E. Wanker. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington’s disease models. Hum. Mol. Genet. (2006) 15, 2743-2751.
15. Legleiter, J., M. Park, B. Cusick, & T. Kowalewski. Scanning probe acceleration microscopy (SPAM) in fluids: mapping mechanical properties of surfaces at the nanoscale. Proc. Nat. Acad. Sci. USA. (2006) 103, 4813-4818.
16. Kowalewski, T & J. Legleiter. Imaging stability and average tip-sample force in tapping mode atomic force microscopy. J. Appl. Phys. (2006) 99, 064903.
