This week we profile a recent publication in Fluids and Barriers of the CNS from Lindsey Williams (pictured, right), Dr. Takashi Fujimoto (left), and the laboratory of Dr. Michelle Erickson (center) at the Geriatrics Research Education and Clinical Center and UW.
Can you provide a brief overview of your lab’s current research focus?
My lab studies the involvement of blood-brain barrier dysfunction in Alzheimer’s disease. One aspect of my lab’s research involves the use of human iPSC-derived brain endothelial-like cells (iBECs), which form a strong blood-brain barrier in vitro. We use this model to understand how aspects of Alzheimer’s disease and its risk factors can cause blood-brain barrier dysfunction.
What is the significance of the findings in this publication?
The main finding of our publication was that iBECs become quiescent with prolonged culture. Quiescent iBECs maintain their strong barrier properties but have reduced glycolysis and glucose transport. Quiescence also confers resistance to blood-brain barrier leakage that is induced by secretions from neurons with a familial Alzheimer’s disease mutation. These findings suggest that brain endothelial cells can have different responses to injury depending on whether they are proliferating or not, highlighting potential vulnerabilities of the blood-brain barrier during development or repair when proliferation is increased.
What are the next steps for this research?
As a future direction, we plan to use the iBEC model to further characterize responses of proliferating vs. quiescent cells to Alzheimer’s disease-associated stimuli.
If you’d like us to mention your funding sources, please list them.
This study was funded by the NIH, grant number R21AG065928.
