Our research is focused on the relationship between protein structure and function. Currently our major area of research is
The molecular basis of protein aggregation and protein deposition diseases.
Protein misfolding and aggregation are among the most critical frontiers in protein chemistry and molecular medicine. Protein misfolding and aggregation are involved in many pathological conditions such as Alzheimer’s and Parkinson’s diseases, type 2 diabetes, etc. The common characteristic of these diseases is the presence of protein deposits that are believed to be responsible for the clinical symptoms. These protein deposition (or conformational) diseases, usually referred to as amyloidoses, are characterized by the presence of deposits of fibrillar aggregates found as intracellular inclusions or extracellular plaques (amyloid) whose main constituent is a specific peptide or protein.
The current focus of Professor Fink’s research is the molecular basis of protein aggregation and protein deposition diseases, especially neurodegenerative diseases, and the development of effective therapies (drugs) to treat these diseases. Protein deposition diseases, both systemic and neurodegenerative, are of increasing prevalence, due to the aging of the population, and thus a critical area for study.
The aggregating systems under investigation include a-synuclein (involved in Parkinson’s disease), immunoglobulin light chains (involved in primary or light chain amyloidosis), insulin, and the A-beta peptide and tau of Alzheimer’s disease.
Methods used include spectroscopy (e. g. FTIR, circular dichroism, ESR, fluorescence), mass spectrometry, dynamic light scattering and small-angle X-ray scattering, microscopy (electron and atomic force), chromatography and electrophoresis, site-specific mutagenesis and high-throughput screening. Proteomics is used to study a variety of questions related to Parkinson’s disease.
Current directions include elucidating the effects of environmental factors on protein aggregation, the role of membranes in protein aggregation, the role of oxidation and oxidative stress on the fibrillation of a-synuclein, the development of drugs against Parkinson’s disease and other amyloidogenic diseases (including combinatorial peptide libraries using phage display), site-directed mutagenesis to aid in the study of protein aggregation mechanisms, the effects of molecular crowding in protein aggregation, the role of molecular chaperones in protein aggregation, the proteomic identification of brain metabolism affected by environmental factors (pesticides and metals) and therapeutic regimes (e. g. L-dopa and dyskinesia).
PDF files of recent papers:
List of Recent Publications
Abstracts of recent and submitted papers
Last updated 1/18/02