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Justin Legleiter, Ph.D.

Associate Professor – Associate Chair

Legleiter Group website 


Dr. Legleiter earned his bachelor’s degree in Chemistry (2000) at Murray State University (Murray, KY) and his PhD in Chemistry (2005) at Carnegie Mellon University (Pittsburgh, PA) under the supervision of Dr. Tomasz Kowalewski. He then spent three years at the Gladstone Institute of Neurological Disease at the University of California, San Francisco as a postdoctoral fellow in the lab of Dr. Paul Muchowski. In August of 2008, he moved to West Virginia University as an assistant professor in the C. Eugene Bennett Department of Chemistry.

There are a large and diverse number of diseases that are commonly classified as conformational diseases. The common feature of these diseases is the rearrangement of a specific protein to a non-native conformation that promotes aggregation and deposition within tissues and/or cellular compartments. Such diseases include Alzheimers disease, Huntingtons disease, Parkinsons disease, amyloidoses, the prion encephalopathies, and many more. A common structural motif in the majority of these diseases is the emergence of extended, -sheet rich, proteinaceous fibrillar aggregates that are commonly referred to as amyloids. These fibrillar species are comprised of intertwined protofibrillar filaments, which often have globular, soluble protein aggregate precursors, more commonly referred to as oligomers. For the vast majority of these diseases, there are no widely effective preventative or therapeutic treatments. The major research goal of our laboratory is to understand the molecular mechanisms that underlie neurodegenerative disorders associated with protein misfolding and aggregation, with a focus on Alzheimers disease and Huntingtons disease. In particular, we are interested in the potential role cellular and subcellular surfaces may play in these events.

We utilize a broad array of research tools and biochemical methods in our studies, but our primary tool is the atomic force microscope (AFM). AFM has provided particularly useful insights related to conformational disease due to its unique ability to be operated not only in air (ex situ) but also in solution (in situ), making it possible to directly visualize the behavior of biological macromolecules at solid-liquid interfaces, under nearly physiological conditions. The ultimate objective of our amyloidogenic peptide AFM studies is to elucidate the physiochemical aspects and molecular mechanisms of pathological self-assembly of biological macromolecules that lead to toxicity..

Teaching Fields

Physical Chemistry 

Courses Offered

  • CHEM 348
  • CHEM 349
  • graduate courses in biophysical chemistry and proximal probe techniques


Chaibva M., Jawahery S., Pilkington IV A.W., Arndt J.R., Sarver O., Valentine S., Matysiak S., and Legleiter J. Acetylation within the First 17 Residues of Huntingtin Exon 1 Alters Aggregation and Lipid Binding. Biophysical Journal (2016) 111:349-362.View at Science Direct

2. Shamitko-Klingensmith N., Boyd, J.W., and Legleiter J. Microtubule modification influences cellular response to amyloid-β exposure. AIMS Biophysics (2016) 3: 261-285.

3. Gao X., Campbell IV W.A., Chaibva M., Jain P., Frey S.L., and Legleiter J. Cholesterol modifies huntingtin binding to, disruption of, and aggregation on lipid membranes. Biochemistry (2016) 55:92-102.

4. Berger T.R., Montie H.L., Jain P., Legleiter J., Merry D.E. Identification of novel polyglutamine-expanded aggregation species in spinal and bulbar muscular atrophy. Brain Research (2015) 1628, Part B:254-264

5. Arndt, J.R., Kondalaji, S.G., Maurer, M.M., Parker, A., Legleiter, J., and Valentine, S.J. Huntingtin N-terminal monomeric and multimeric structures destabilized by covalent modification of heteroatomic residues. Biochemistry (2015) 54:4285-4296.

6. Arndt J.R., Chaibva M., and Legleiter J. The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease. Biomolecular Concepts (2015) 6:33-46.

7. Arndt J.R., Brown R.J., Burke K.A., Legleiter J., and Valentine S.J. Lysine Residues in the N-Terminal Huntingtin Amphipathic α-Helix Play a Key Role in Peptide Aggregation. Journal of Mass Spectrometry (2015) 50:117-126.

8. Shakitko-Klingensmith N. and Legleiter J. Investigation of temperature induced mechanical changes in supported bilayers by variants of tapping mode atomic force microscopy. Scanning (2015) 37:23-35.

9. Chaibva M., Shamitko-Klingensmith N., and Legleiter J. Recovering Time-Resolved Imaging Forces in solution by Scanning Probe Acceleration Microscopy: Theory and Application in Surface Science Characterization Techniques for Nanomaterials”. C. Kumar editor. Springer. (2015) 69-89.

10. Yates E.A. and Legleiter, J. Preparation protocols of Aβ(1-40) promote the formation of polymorphic aggregates and altered interactions with lipid bilayers. Biochemistry (2014) 53:7038-7050.

Chaibva M., Burke K.A., & Legleiter J. Curvature enhances binding and aggregation of huntingtin at lipid membranes. Biochemistry. (2014) 53:2355-2365.

Burke K.A., Hensal K.M., Umbaugh C.S., Chaibva M., & Legleiter J. Huntingtin disrupts lipid bilayers in a polyQ-length dependent manner. Biochimica et Biophysica Acta (BBA) – Biomembranes (2013) 1828:1953-1961.

Burke K.A., Kauffman K.J., Umbaugh C.S., Frey S.L., & Legleiter J. The Interaction of Polyglutamine Peptides With Lipid Membranes is Regulated by Flanking Sequences Associated with Huntingtin. Journal of Biological Chemistry (2013) 288:14993-15005.

Yates E.A., Owens S.L., Lynch M.F., Cucco E.M., Umbaugh C.S., & Legleiter J. Specific domains of Aβ facilitate aggregation on and association with lipid bilayers. Journal of Molecular Biology (2013) 425:1915-1933.

Lotz, G.P. & Legleiter, J. The role of amyloidogenic protein oligomerization in neurodegenerative disease. Journal of Molecular Medicine (2013) 91:653-664. 

Burke, K.A., Yates, E.A. & Legleiter, J. Amyloid-forming proteins Alter the Local Mechanical Properties of Lipid Bilayers. Biochemistry (2013) 52:808-817. 

Burke, K.A., Yates, E.A. & Legleiter, J. Biophysical insights into how surfaces, including lipid membranes, modulate protein aggregation related to neurodegeneration. Frontiers in Neurology (2013) 4:17.

Burke, K.A. & Legleiter, J. Atomic force microscopy assays for evaluating polyglutamine aggregation in solution and on surfaces. Methods in Molecular Biology (2013) 1017:21-40. 

Shamitko-Klingensmith, N., Wambaugh, K. M., Burke, K. A., Magnone, G. J., & Legleiter, J. Correlation of atomic force microscopy tapping forces to mechanical properties of lipid membranes, ASME Conference Proceedings (2012),DETC2012-70233.

Shamitko-Klingensmith, N., Molchanoff, K. M., Burke, K. A., Magnone, G. J., & Legleiter, J. Mapping the Mechanical Properties of Cholesterol-Containing Supported Lipid Bilayers with Nanoscale Spatial Resolution, Langmuir (2012) 28:13411-13422.

Nucifora, L. G., Burke, K. A., Feng, X., Arbez, N., Zhu, S., Miller, J., Yang, G., Ratovitski, T., Delannoy, M., Muchowski, P. J., Finkbeiner, S., Legleiter, J., Ross, C. A., & Poirier, M. A. Identification of Novel Potentially Toxic Oligomers Formed in Vitro from Mammalian-derived Expanded huntingtin Exon-1 Protein, Journal of Biological Chemistry (2012) 287:16017-16028.

Legleiter, J., Burke, K. A., & Yates, E. A. Investigation of protein/lipid interactions via scanning probe acceleration microscopy: theory and experiment, ASME Conference Proceedings (2012), DETC2012-70228.

Legleiter, J., Fryer, J. D., Holtzman, D. M., & Kowalewski, T. The Modulating Effect of Mechanical Changes in Lipid Bilayers Caused by ApoE-Containing Lipoproteins on Ab Induced Membrane Disruption, ACS Chemical Neuroscience (2011) 2:588-599.

Pifer, P. M., Yates, E. A., & Legleiter, J. Point Mutations in Aβ Result in the Formation of Distinct Polymorphic Aggregates in the Presence of Lipid Bilayers, PLoS ONE (2011) 6:e16248.

Yates, E. A., Cucco, E. M., & Legleiter, J. Point Mutations in Ab Induce Polymorphic Aggregates at Liquid/Solid Interfaces, ACS Chemical Neuroscience (2011) 2:294-307.

Burke, K. A., Godbey, J., & Legleiter, J. Assessing mutant huntingtin fragment and polyglutamine aggregation by atomic force microscopy, Methods (2011) 53:275-284.

Miller, J., Arrasate, M., Brooks, E., Libeu, C. P., Legleiter, J., Hatters, D., Curtis, J., Cheung, K., Krishnan, P., Mitra, S., Widjaja, K., Shaby, B. A., Lotz, G. P., Newhouse, Y., Mitchell, E. J., Osmand, A., Gray, M., Thulasiramin, V., Saudou, F., Segal, M., Yang, X. W., Masliah, E., Thompson, L. M., Muchowski, P. J., Weisgraber, K. H., & Finkbeiner, S. Identifying polyglutamine protein species in situ that best predict neurodegeneration, Nature Chemical Biology (2011) 7:925-934.

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. Human Molecular Genetics (2010) 19:65-78.

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. Journal of Biological Chemistry (2010) 285:38183-38193. 

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. Journal of Biological Chemistry (2010) 285:14777-14790.

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. Journal of Applied Physics (2010) 107:044508.

Legleiter, J. Assessing Aβ aggregation state by atomic force microscopy. Methods in Molecular Biology (2010) 670:57-70.

Abraham, A., E. Mihaliuk, B. Kumar, J. Legleiter, & T. Gullion. Solid-State NMR study of Cysteine on Gold Nanoparticles. Journal of Physical Chemistry C (2010) 114:18109-18114.