ISR Distinguished Lecturer: Peter Searson, "Reverse Engineering the Blood-Brain Barrier"
Wednesday, February 15, 2017
1146 AV Williams Building
Reverse Engineering the Blood-Brain Barrier
Co-sponsored by the Institute for Systems Research, the Fischell Department of Bioengineering, the Department of Materials Science and Engineering and the Brain and Behavior Initiative
Joseph R. and Lynn C. Reynolds Professor
Director, Institute for NanoBioTechnology
Department of Materials Science and Engineering
Whiting School of Engineering
Johns Hopkins University
The blood-brain barrier is a 600 km network of capillaries that supplies nutrients and other essential molecules to the brain while maintaining tight control of the microenvironment by preventing fluctuations in chemistry (water, salts, and hormones), transport of immune cells, and the entry of toxins and pathogens. It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we discuss the challenges associated with reverse engineering an in vitro model of the blood-brain barrier and discuss recent progress and challenges.
Searson is the Reynolds Professor of Engineering and holds joint appointments in the Department of Physics and Astronomy, and the Department of Oncology. He is a fellow of the American Physical Society, and a fellow of the American Association for the Advancement of Science. His research interests are in tissue engineering, biomaterials, and nanomedicine:
The blood-brain barrier (BBB). The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system and protects the central nervous system from potentially harmful chemicals while regulating transport of essential nutrients. We are using tissue engineering, stem cell technology, and microfabrication to reverse engineer the blood-brain barrier. Reverse engineering is the process of understanding the function of individual components in anything man-made (usually through disassembly), to enable reproduction. This reductive approach to understanding the role of individual components is particularly well suited for the BBB, which is inherently complex and involves multiple cell types. In particular it allows us to elucidate the underlying physical and biochemical processes that regulate the phenotype of brain capillaries and microvessels, while simultaneously allowing us to systematically increase the complexity of the model.
In vitro models of the tumor microenvironment. Metastasis, which is responsible for more than 90% of cancer-related deaths, involves a sequence of steps including invasion, dormancy, intravasation, arrest, extravasation, and colonization at a secondary site. These are dynamical processes that occur at or near the vascular system and are very difficult to visualize in vivo. Our incomplete understanding of the steps in the metastatic cascade is a major barrier to developing therapies to prevent the spread of the disease and improve patient outcomes. Since steps such as intravasation and extravasation are inherently dynamic processes, visualization is critically important in elucidating mechanisms and pathways. Recent advances in the development of in vitro microvessel models provide the tools to create more physiological models of the tumor microenvironment and to visualize steps in the metastatic cascade. We are developing tissue-engineered models of the tumor microenvironment to visualize steps in the metastatic cascade. These models include tumor vasculature, post-capillary venules, and capillary networks. These models are also being used for testing and imaging drug and gene delivery vehicles.
Drug delivery systems. The systemic delivery of a drug to a solid tumor involves several steps that occur in series and ultimately determine drug efficacy and survival. We are developing various strategies for engineering liposome-based and peptide-based drug delivery systems to improve tumor accumulation and uptake in target tissues. We are particularly interested in strategies to delivery drugs to the brain.