Our lab focuses on understanding the mechanisms of protein misfolding and aggregation in degenerative diseases. Alzheimer's disease (AD), Parkinson's disease (PD), Dementia with Lewy bodies (DLB), Progressive Supranuclear Palsy (PSP), Macular degeneration, Type II diabetes, Huntington's disease, Prion diseases, Serum amyloidoses are only a few of the conditions that result from amyloid and tau oligomer misfolding and aggregation. As this list grows, it becomes vital to understand the mechanisms of amyloid formation, accumulation, and protein assembly. Soluble oligomers and protofibrils are significant in the pathogenesis of these diseases. These species are not only common among all amyloidogenic proteins, but they also share common structural features regardless of their sequence.
An emerging view in neurodegeneration is that the large meta-stable tau aggregates such as, plaques and neurofibrillary tangles (NFT) are not toxic; rather, it is the intermediate amyloid and tau aggregates (oligomers) that are pathogenic. One of the many approaches we use is to exploit our knowledge of amyloid and tau oligomer structure to prepare novel antigens that elicit a specific immune response. This approach allows us to avoid unwanted autoimmune responses or interference with folded, functional proteins. This concept of generating conformation-specific antibodies not only makes it possible to study these diseases in vivo, but it may enable us to develop a safe therapeutic vaccine to prevent or treat these devastating diseases. Our lab also screens commercially available and novel drug-like small-molecules to identify inhibitors of oligomer formation.
We are also interested in studying pore-forming toxins, bacterial amyloid and biofilm. We are using our novel antibodies to prevent toxin-induced hemolysis and neutralize bacterial amyloid's infectious properties and prevent human diseases.