Ph.D. (Doctor of Philosophy)
Research and teaching
Brain blood flow is exquisitely controlled by local changes in brain activity in order to deliver oxygen and glucose to desired regions, thereby meeting the brain’s high metabolic demand. A spectrum of neurological problems are closely linked to abnormalities in brain blood flow, yet surprisingly we know very little about how brain cells signal to blood vessels to regulate this process. My laboratory uses advanced fluorescence microscope technologies (two-photon) to image within the brain at the sub-cellular level in rodents to study how this ‘neuro-vascular unit’ functions. By understanding the molecular mechanisms of how the brain is fueled, my research program will discover new targets for disease intervention.
The cellular mechanisms recruited during cerebral blood flow (CBF) control are complex and the specific contribution of neurons, astrocytes and vascular cells is highly controversial, as they have been difficult to tease apart using traditional methods. This is due, in part, to an inability to activate or inhibit specific cell populations to causally determine how different cell-types contribute to this process. Using technical innovations such as opto-genetics, chemo-genetics and genetically encoded calcium indicators, my lab is determining how neurons, astrocytes and vascular cells communicate with each other and we are identifying novel cell-type specific contributions, as well as new cellular pathways involved in CBF regulation. Two complimentary preparations enable our advances: 1) acutely isolated brain slices for two-photon imaging, patch electrophysiology and pharmacology, as well as 2) two-photon imaging in fully awake and active animals which can be coupled with opto/chemo-genetics and pharmacological assessments. Our long-term goals are to discover new mechanisms and functions of the neuro-vascular unit to better understand how the brain regulates and services its immense energy needs.