Kaustuv Saha


My research involves exploring the underlying molecular mechanism for the devastating effect of illicit drugs such as methamphetamine (METH) and amphetamine (AMPH). The dopamine transporter (DAT) is one of the main targets of METH and AMPH. DAT regulates the spatial and temporal dimensions of dopaminergic neurotransmission in the brain. We have shown that AMPH and METH along with dopamine are substrates for DAT and differentially alter biophysical properties of DAT. My studies also involve understanding the structure-activity relationships to identify DAT substrates with minimum addictive/neurotoxic profile, but optimum DA efflux that is required for therapeutic efficacy. To achieve these goals I study the biophysical properties of DAT, DAT interaction with other protein partners and trafficking. For these studies I use patch-clamp electrophysiology, TIRF (Total Internal Reflection Fluorescence), confocal FRAP (Fluorescence Recovery After Photo-bleaching) and live cell confocal microscopy in heterologous expression system and primary neuronal culture, brain slices as well as rodent behavior. My long-term goal is to identify structurally relevant, economically viable compounds from those already existing in the market as therapeutic tools for pathological conditions involving malfunctioning of DAT,  psychostimulant addiction, ADHD and Parkinsonism.