Kaie Hall
Program: Unspecified
Current advisor:
Undergraduate university: Howard University
Research summary
Protein misfolding and aggregation underlie the pathology of numerous neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease. The yeast disaggregase Hsp104 has emerged as a model system for understanding how protein quality control machinery can reverse amyloid formation and restore proteostasis. In this project, I investigated the functional significance of specific amino acids within the middle domain (MD) of Hsp104, a region critical for coordinating inter-subunit communication and substrate remodeling. Using site-directed mutagenesis, I introduced targeted amino acid substitutions into Hsp104 and examined how these mutations altered the protein’s ability to disaggregate disease-associated substrates, including TDP-43, α-synuclein, and FUS. Functional assays were performed to assess changes in disaggregase activity, providing insight into how the MD contributes to substrate recognition and mechanical remodeling. These studies advance our understanding of the structure–function relationship of Hsp104 and may inform the design of enhanced disaggregase variants with potential therapeutic relevance for neurodegenerative disorders driven by protein aggregation.
Graduate publications