My research interests at a broader level  are at the integration of life sciences and engineering. My undergraduate work in chemical engineering, masters in biomedical engineering, and Ph. D in integrative biosciences have all contributed to my integrative research approach. My Ph.D  research in  transport of nutrients from blood to the brain helped me focus in the specific area of transport mechanisms /kinetics of solutes into and out of  brain.

 

Blood-brain barrier (BBB) is the main route of transport for drugs, nutrients to enter the brain. It is a physiological barrier made up endothelial cells of the brain microvasculature joined together by tight junctions.  The main function of the BBB is to maintain homeostasis in the central nervous nervous system  (CNS) by tightly regulating the transcellular and paracellular flux. Without the BBB, toxins can enter the brain freely and therefore damage the CNS.

 

To study the transport of solutes across the BBB,  in vitro model systems comprising microvascular endoethial cells in monolayer culture either alone or in co-culture with astrocytes have been employed by various research labs; however there are no models to date that  closely mimic the BBB in vivo.  We have therefore started to characterize the in vitro model of the rat brain microvacular endothelial cells in culture and established its suitability to study transferrin-iron transport. The model also showed that luminal (blood-side) and abluminal (brain-side) membrane proteins of this barrier in vitro are differentially expressed suggesting a common mode of  trafficking for the respective membrane proteins. This data also provides evidence for the loss of polarity of this barrier in the in vitro model systems.

 

We have previously shown that glucose transporter GLUT-1, the isoform responsible for glucose transport into the brain is also polarized at the BBB and the polarity is manifested even in the culture system. We are therefore currently studying the peptide modifications of the putative luminal and abluminal GLUT-1 transporters at the BBB and in the future study the function differences in the two forms of the transporters both in the normal conditions as well as diseased states such as diabetes, and stroke.

 

The future research in my lab will be directed towards understanding  the  mechanisms and kinetics of  therapeutic molecules and devising a delivery system for successful transport into the brain.