Ronald Wetzel
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Phone (412) 383-5271
Fax (412) 648-8998

University of Pittsburgh
2046 Biomedical Science Tower 3

 

Ronald Wetzel


Professor emeritus
Department of Structural Biology



Aggregate structure. The protein aggregates associated with Alzheimer's Disease, Huntington's Disease, and other diseases tend to be highly ordered structures possessing, so far as we can establish, the same degree of packing specificity normally found in globular proteins. We use standard techniques like CD, FTIR, and EM to study the gross morphology of these aggregates. We attempt to get at finer structural points by adapting other methods previously applied to globular proteins Fibril assembly and inhibition.
 
We are interested in fibril assembly mechanism, kinetics and thermodynamics. We have developed and optimized a number of assays for following fibril formation that we routinely use to assess the kinetics and thermodynamics of fibril formation and to screen for inhibitors, both in the Alzheimer's Ab system and in the Huntington's Disease polyglutamine system.
 
The basis of aggregate cytotoxicity. We are interested in the mechanisms by which cells die or become dystrophic in response to aggregates. The mechanism we are particularly interested in has been called the "recruitment" or "sequestration" mechanism. We are studying polyglutamine aggregation in vitro to develop the biophysical underpinnings of this mechanism, and are also studying what happens when polyglutamine aggregates made in vitro are introduced into cells.

Visit Ron's lab website


Education & Training

Undergraduate
Drexel University, Philadelphia
B.S. 1969 in Chemistry

Postgraduate
Max Planck Institute
Goettingen, German 1973 - 1975

Yale University
New Haven 1975 - 1978



Awards & Honors


1998    Zenith Award, Alzheimer's Association 
1999    Lieberman Award, Hereditary Disease Foundation



Representative Publications


Mishra, R., Jayaraman, M., Roland, B.P., Landrum, E., Fullam, T., Kodali, R., Thakur, A.K., Arduini, I., & Wetzel, R., Inhibiting nucleation of amyloid structure in a huntingtin fragment by targeting α-helix rich oligomeric intermediates.  J. Mol. Biol. 415: 900-917. 2012.

Jayaraman, M., Mishra, R., Kodali, R., Thakur, A.K., Koharudin, L.M.I., Gronenborn, A.M., & Wetzel, R., Kinetically competing huntingtin aggregation pathways control amyloid polymorphism and properties. Biochem. 51: 2706-2716. 2012.

Mishra, R., Hoop, C.L., Kodali, R., Sahoo, B., van der Wel, P.C.A., & Wetzel, R., Serine phosphorylation suppresses huntingtin amyloid accumulation by altering protein aggregation properties. J. Mol. Biol. 424:1-14. 2012.

Kar, K., Hoop, C.L., Drombosky, K.W., Baker, M.A., Kodali, R., Arduini, I., van der Wel, P.C.A., Horne, W.S., & Wetzel, R., -hairpin-mediated nucleation of polyglutamine amyloid formation.  J. Mol. Biol., 425: 1183-1197. 2013.

Nafie, L.A., Kurouski, D. , Kar, K., Wetzel, R., Dukor, R.K., and Lednev, I.K., Levels of supramolecular chirality of polyglutamine aggregates revealed by vibrational circular dichroism. FEBS Letts.: 587: 1638-1643. 2013.


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Active Grants


Mechanisms of Amyloid Nucleation
04/01/12 – 03/31/17
National Institutes of Health
R01

Structures and Properties of Polyglutamine Proteins and Their Aggregates
06/15/01 – 05/31/16
National Institutes of Health
R01

Training in Molecular Biophysics and Structural Biology
07/01/11 – 06/30/16
National Institutes of Health
T32