Anson Pierce., Ph.D.

Publications (Pubmed)

Affiliations: Department of Biochemistry & Molecular Biology, Sealy Center for Vaccine Development, Mitchell Center for Neurodegenerative Diseases
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Anson Pierce, Ph.D.

Assistant Professor

Protein aggregation is a common theme across various neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s (AD), and Huntington’s diseases (HD). Despite this, the degree to which aggregates are involved in neurotoxicity is uncertain. Mutated or oxidatively damaged proteins can often both lose their function or gain toxic ones due to misfolding and exposure of hydrophobic domains. If not refolded or sent to degradative pathways by the cell’s chaperone or heat shock proteins, exposed hydrophobic domains can stabilize and facilitate the formation of oligomers and cause further toxicity, while aggregates that form further downstream may be less toxic or even protective.

To better understand the role of altered protein hydrophobicity and neurodegenerative diseases, we have developed a fluorescence based proteomic assay to detect changes in protein hydrophobicity from in vivo sources of protein. Using this technique, we can both identify and map exposed hydrophobic domains of proteins, and use this information to develop better site-specific antibody vaccines or other molecular chaperones against misfolded proteins. The major transcription factors responsible for expression of cellular chaperones are heat shock factor 1 (HSF1) and HSF2. When levels of unfolded proteins rise in the cell caused by proteotoxic stress (heat, oxidation), HSFs become activated and induce the heat shock response (HSR), leading to production of more heat shock proteins. We have also developed transgenic mice that overexpress HSF1 to further address the role of altered protein hydrophobicity in neurodegenerative diseases, and are investigating their protective effects in mouse models of ALS, AD, and HD.


We utilize proteomic techniques in the lab such as 2D gel electrophoresis, mass spectrometry, protein derivitization, and immunoblotting, as well as cell culture, transgenic animal models, and molecular techniques. In this dual-channel fluorescent image of a 2D gel from proteins isolated from normal (wt) and ALS mouse spinal cord, mutations in human superoxide dismutase (SOD1) expressed by the H46R/H48Q ALS mouse impart a fraction of the SOD1 spots (red and bracketed) with increased surface hydrophobicity (yellow fluorescence). Calculation of the hydrophobic ratio and correcting for protein abundance reveals increased hydrophobicity as indicated by those spots with asterisks.