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The Levinson Emerging Scholars Program

Alyssa Sheih - Bioengineering

Alyssa SheihAs a student in the Bioengineering department, Alyssa Sheih’s research interests involve addressing current medical problems through new diagnostic methods and therapeutics.  Her passion for this area led her to Professor Hong Shen’s lab in the Chemical Engineering department, as a 2008 UW Amgen Scholar.  Since then, Alyssa has been studying the design of drug delivery systems and their interactions with the immune system.  Currently, she is excited for the opportunity to study cell-based therapy for neurodegenerative disease, with the funding of the Levinson scholarship.  After graduation, Alyssa plans on pursuing a Ph.D. degree in Bioengineering with a research focus on immunology.

Mentor: Hong Shen, Chemical Engineering

Project Title: Engineering T Cells for Brain Imaging and Therapeutics

Abstract: According to the Alzheimer's Association, every 70 seconds, someone in America develops Alzheimer's disease. Beta-amyloid peptides are believed to be the main cause of this disease, forming plaques between nerve cells and triggering inflammation. By destroying brain cells, Alzheimer's causes severe problems with memory, thinking, and behavior. Currently, diagnostic capabilities for this disease are limited with physicians utilizing neurological exams and brain imaging. Because early diagnosis of Alzheimer's disease and clinical evaluation of therapeutics is important, there is a need for an accurate diagnostic tool for Alzheimer's disease. Here we propose using a contrast agent for brain imaging that can bind to beta-amyloid peptides, allowing for the detection of Alzheimer's disease. Previously, non-cellular vehicles such as nanoparticles have been used to deliver contrast agents to the brain, by targeting receptors on the blood brain barrier to achieve transport. However, other types of cells also express these receptors, resulting in nonspecific targeting of the brain. These particles can be immunogenic and are vulnerable to clearance by our immune system. Here we propose another solution by using T lymphocytes, which are immune cells capable of crossing the blood brain barrier and localizing near sites of inflammation in the brain. These cells will serve as vehicles modified to carry a contrast agent along with antibodies specific for beta-amyloid peptides. Initially, a proof of concept study will be completed to show that the surface of T cells can be modified to carry a fluorescent label and an antibody for ovalbumin, a more available protein that will serve as a substitute for beta-amyloid peptides in these experiments. This surface modification procedure will be optimized to maximize the binding capability of T cells without compromising its functionality. This project presents one of the first steps towards developing an accurate diagnostic tool for Alzheimer's disease.