Brief Bio

Dr. Donald Miller’s research interests focus on understanding the cellular factors that control blood-brain barrier (BBB) permeability under both normal and pathophysiological conditions. Utilizing both cell culture and whole animal models, his laboratory examines various transport processes for moving drugs and solutes into and out of the brain. His research program includes examination of BBB changes during brain tumour development and identification of methods for increasing the delivery of chemotherapeutic agents to more effectively treat brain tumours; identification and characterization of drug efflux transport proteins in the blood-brain barrier and the molecular mechanisms influencing their activity and expression; and the design and development of nanoparticle drug delivery platforms for treating CNS diseases. His laboratory has also examined inflammatory processes including cytokine and lipid mediators of inflammation and their impact on brain endothelial response and has recently expanded into inflammatory cascades in other organ/tissues including chondrocytes (joint related inflammation) and microglia/macrophage (CNS and systemic inflammation).

Research Directions

Understanding the cellular regulators of blood-brain barrier function under normal and pathophysiological conditions. Using microfluidic culture models and various rodent models to examine how various neurological pathologies can influence blood-brain barrier function. Identification of important cell signaling pathways such as Wnt and Sonic Hedgehog and resulting changes at the protein and transcriptome level.

Development of methods for increasing drug delivery (both small molecules and biologicals) to the brain for treatment of CNS disorders. Methods for increasing blood-brain barrier permeability of therapeutics include using receptor-mediated transport routes through the brain endothelial cells as well as various approaches to transiently open up the blood-brain barrier for delivery of traditional small molecule therapeutics as well as biologicals and nanoparticles. 

Improving therapeutic treatment of brain tumours using nanomedicine approaches. Nanoparticles being evaluated include various metal oxide nanoparticles as well as lipid-based nanoparticles for small molecule and biological delivery to the brain. 

Identification of biomarkers for monitoring brain tumour response to therapy. Laboratory is actively examining blood and urine-based biomarkers for detecting brain tumor progression.  

Personnel

Vinith Yathindranath, Research Associate

Prasanta Pauls, Post Doctoral Fellow

Stacey Line, Graduate Student

Nur Safa, Graduate Student

Publications