SCVD Faculty

Anson Pierce, PhDAnson Pierce, PhD

Our lab focuses on the changes in surface hydrophobicity that occur in proteins in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Alzheimer’s disease, and how this information can be used to generate more efficacious and selective immunotherapies. We monitor changes in surface hydrophobicity in proteins from tissues by photochemically cross-linking the dye 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonate (bisANS) followed by a fluorescence-based proteomic analysis of labeled proteins.

A common theme in several neurodegenerative diseases involves the unfolding and increased exposure of hydrophobic domains directly from disease-causing proteins or indirectly resulting from loss/gain of toxic function. In addition to loss of function from unfolding, proteins can interact with novel targets based on newly exposed hydrophobic surfaces, which are often stabilized by hydrophobic-hydrophobic interactions, the most profound example being protein aggregation. Based on the site-specific information we obtain from proteomic analyses, we hope to 1) identify novel and characterize established targets on the basis of altered hydrophobicity. 2) Develop antibody-based vaccines targeting the region(s) of the protein exhibiting altered hydrophobicity as a passive immunotherapy. This approach has several advantages as it examines the structural changes in a more in vivo context, and is capable of directing vaccine therapies at surface-exposed, targeted sites of proteins.


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