Advisor: YongTae “Tony” Kim, Ph.D. (Georgia Institute of Technology)

Committee:

Allan I. Levey, Ph.D. (Emory University)

Young C. Jang, Ph.D. (Georgia Institute of Technology)

Michelle C. LaPlaca, Ph.D. (Georgia Institute of Technology and Emory University)

Shuichi Takayama, Ph.D. (Georgia Institute of Technology and Emory University)

Development of an microengineered human blood-brain barrier model for drug testing and disease modeling

The blood-brain barrier (BBB) is a unique vascular border in the central nervous system (CNS) that has a highly selective barrier function that prevents most drugs from entering the brain. This barrier function makes it challenging to develop effective therapeutics for CNS diseases. One in-novative approach to addressing this challenge is to leverage experimental models that can pro-vide reliable predictions of drug efficacy or toxicity in humans. Despite recent advances in the development of these models, development of in vitro human BBB model that can mimic the structure and function of the human BBB with physiological relevance remains difficult due to the complex nature. The main focus of this thesis is to develop a microengineered human BBB model designed to reconstitute the functional barrier of the BBB by incorporating the key physio-logical components. Our BBB model will be characterized and validated by permeability test, confocal microscopy, and gene expression analysis. Furthermore, this model will be used to test the interaction of nanoparticles with the BBB and to mimic a condition of neuroinflammation mediated by human microglia in AD.