The primary research interest of my group is to understand molecular mechanism for the reduced synaptic connections in Alzheimer’s disease (AD) leading to loss of memory, a seminal feature of AD. AD is characterized by the presence of intracellular neurofibrillary tangles and extracellular amyloid plaques believed to be responsible for loss of synapses. The long-term objective of my research is to discover molecular targets which may modulate generation of amyloid beta peptide (Ab), the core constituent of amyloid plaques. Additionally, we are interested to investigate whether critical regulators of spine generation and maintenance can be used as therapeutic targets in AD since loss of synapses is a crucial factor for the cognitive deficits in AD.
In spite of rigorous research efforts worldwide, currently there is not a single drug available that can effectively reverse or even slow down the loss of memory in patients with AD. Therefore our goal is to use proof-of-concept molecules which modulate Ab generation and/or number of spines to discover lead compounds using varieties of small molecule and peptide libraries by high throughput screening (HTS). To accomplish these objectives we will use histological, pharmacological, biochemical and molecular approaches by using varieties of techniques including immunoprecipitation, yeast two-hybrid screening, in vivo lentiviral delivery, transgenic mouse models, knockout mouse models, high throughput robotics screening and TR-FRET imaging.