Peptide Imaging Agents Specific for Tau Aggregates
Alzheimer’s disease (AD) is linked to proteins that misbehave and stick together into protein particles that are toxic to brain cells. Early detection of this dreaded disease requires the generation of imaging molecules that can enter the brain and selectively tag the toxic protein particles in different parts of the brain. We aim to use an innovative design and evolution method for generating imaging probes specific for particles of one of the most harmful Alzheimer’s proteins (tau). We will use these novel probes to image toxic tau protein particles in the brains of mice used as models of AD, with the long-term goal of translating this technology to humans for early and accurate disease detection.
As the first step of our investigation, we will generate small probes that recognize different forms of tau protein aggregates. Our approach is to use a small and stable scaffold that will be mutated to generate large libraries of variants with sequence differences in the binding loops. We will introduce different functional groups (amino acids) at several sites in the binding loops that have a wide range of properties, including amino acids with positive and negative charge as well as those with hydrophobic (water hating) or hydrophilic (water loving) groups. Next, we will use high-throughput screening methods to sort these large libraries in order to select rare variants (ie, the “needles in the haystack”) that selectively recognize toxic forms of the tau protein that are associated with Alzheimer’s disease (AD). Finally, we will evaluate these novel probes as imaging agents for detecting toxic tau protein particles in the brains of mice used as models of AD. Our long-term goal is to translate this technology to humans for early and accurate detection of Alzheimer’s disease.
About the Researcher
Peter Tessier, PhD, is the Albert M. Mattocks Professor of Pharmaceutical Sciences and Chemical Engineering in the Departments of Chemical Engineering and Pharmaceutical Sciences (equal appointments), and a member of the Biointerfaces Institute, at the University of Michigan in Ann Arbor, MI. He received his B.S. degree in chemical engineering from the University of Maine (1998, co-valedictorian), and his PhD in chemical engineering from the University of Delaware (2003, NASA Graduate Fellow). Tessier performed his postdoctoral studies at the Whitehead Institute for Biomedical Research at MIT (2003-2007, American Cancer Society Fellow). Tessier started his independent career as an assistant professor in the Department of Chemical & Biological Engineering at Rensselaer Polytechnic Institute in 2007, and he was an endowed full professor (Richard Baruch, MD, Career Development Professor of Chemical & Biological Engineering) prior to his move to the University of Michigan in 2017. Tessier’s research focuses on designing, optimizing, characterizing and formulating a class of large therapeutic proteins (antibodies) that hold great potential for detecting and treating human disorders ranging from cancer to Alzheimer’s disease. He has received a number of awards in recognition of his pioneering work, including a Humboldt Fellowship for Experienced Researchers (2014-15), a Young Scientist Award from the World Economic Forum (2014), a Biochemical Engineering Journal Young Investigator Award (2016), a Young Investigator Award from the Biochemical Technology division of the American Chemical Society (2015), a Pew Scholar Award in Biomedical Sciences (2010-14), a National Science Foundation CAREER Award (2010-15), a Rensselaer Early Career Award (2012), and Rensselaer School of Engineering Research (2012) and Teaching (2013) Awards.
My passion is to develop technologies that improve human health. Several members of my family have Alzheimer’s disease (AD), and my love for them motivates me each day. My lab seeks to perform high risk/high return research related to diagnosing and treating AD. The financial support from the BrightFocus Foundation enables us to conduct research that would move the needle in terms of Alzheimer’s diagnosis if successful, but this research is too risky to be funded by conventional funding agencies. We are extremely grateful to the donors of the BrightFocus Foundation that make our research possible. You (the donors) motivate us to do our very best each day to improve the future for Alzheimer’s patients.
First published on: November 8, 2017
Last modified on: May 6, 2020