The goal of this research is to develop molecular probes that exhibit turn-on fluorescence upon binding to amyloids. Amyloids are a natural class of protein- or peptide containing materials that are heterogeneous in size, morphology, and composition. Deposition of amyloid plaques in the brain represents a universal feature of many neurodegenerative diseases such as Alzheimer’s disease and precedes clinical symptoms by several years. We have recently designed a new family of fluorescent probes that can label amyloids in tissue. Importantly, we demonstrated that these probes can be tuned in a way that allows not only enhanced fluorescence visualization of amyloids but also colorimetric discrimination of the amyloids as a function of their protein composition. Such discriminating ability may enable accurate determination of specific neurodegenerative diseases, thereby aiding in selection of a proper course of treatment. A major focus of this research is to develop new bright and tunable fluorescence probes with high binding affinity and selectivity to specific amyloid targets. The ultimate goal is to translate these probes into clinically useful technologies by developing rapid, low cost, and reliable methods for diagnosing and monitoring the progression of amyloid-associated diseases.
Recent studies have shown that a class of small molecules developed in the Yang lab can improve memory and learning in both wild-type mice and in a transgenic mouse model for Alzheimer’s disease. Subsequent experiments in primary hippocampal neurons confirm that this class of compounds exhibit the capability to promote the formation of dendritic spines (the neuronal structure that forms the receiving end of a synapse) and increase the density of synapses between neurons. Such phenomenal phenotypic activity of these compounds offers tremendous potential for treating a host of memory impairment disorders such as Alzheimer’s disease. Current efforts in the group are focused on 1) development of improved promoters of dendritic spine formation, 2) elucidation of the molecular and cellular mechanism of action of these molecules, and 3) examining the role these compounds can have in disease intervention.
A major goal of this research is to develop new biocompatible polymeric and lipid-based materials capable of improving the targeting of cancer therapeutics to solid tumors by controlling the location and time over which active drug release occurs. A central component of this research entails development of stimuli-responsive linkers that can exploit the unique environment of some tumor cells to trigger the controlled release of therapeutic agents from drug delivery vessels. A separate recent effort involves the investigation of a new class of compounds developed by the Yang lab that can arrest the migration of metastatic cancer cells.
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