Research Overview

The Joachimiak lab integrates multiple strategies to reveal the structure and function of proteins that misfold in neurodegenerative diseases. To understand tau misfolding, we employed (clockwise from top) crosslinking mass spectroscopy, structural biology, biochemistry, and structure prediction. The ribbon structure in the center depicts tau (in color) bound with the molecular chaperone DnaJC7 (grayscale).

Protein misfolding is a key element of Alzheimer’s and other neurodegenerative diseases. Our lab seeks to uncover the structure-function relationship of macromolecules involved in protein misfolding. We study how conformational changes lead proteins to self-assemble into larger structures, and how cofactors tune the formation of these structures. We believe this work will lead to breakthroughs in understanding and treating neurodegenerative diseases.

To this end, we are developing strategies that integrate crosslinking mass spectrometry with structural, computational, and biochemical approaches. Using this hybrid approach, we have purified and characterized two distinct forms of tau protein monomer: an inert form, and another that readily self-assembles into large aggregates.

This finding, driven by our novel methods, open exciting avenues of research and treatment, such as detecting pathological forms of tau in people before they develop symptoms of Alzheimer’s disease or other tauopathies.

Our lab focuses on four main areas:

  • Protein aggregation
  • Hybrid structural analysis of proteins
  • Structural rules that control protein aggregation
  • Molecular chaperones that modulate aggregation