ChE Seminar Series: A story of tau: Protein-protein interactions and cellular effects that lead to disease


9:35 am-10:30 am
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Trustee Professor of Chemical Engineering and Department Head
Carnegie Mellon University

Title:A story of tau: Protein-protein interactions and cellular effects that lead to disease

Abstract: Proteins are vital biomolecules that do most of the critical functions in the body, including structural roles, enzymatic activity, and regulation of metabolism. Tau proteins are present primarily in the brain, and function there to regulate the dynamics, stability and transport properties of cytoskeletal microtubules. Under pathological conditions, tau forms paired helical filaments (PHFs) that aggregate to form intracellular neurofibrillary tangles (NFT), which are one of the hallmarks of Alzheimer’s Disease (AD). In addition to AD, these tau NFTs occur in at least 26 other phenotypically distinct neurodegenerative diseases, termed tauopathies. For all neurodegeneration, tau transmission from across the brain occurs in a prion-like manner, exacerbating degeneration and worsening symptoms. However, the detail on the molecular and cellular contributions are still an area of active research, limiting current therapeutic success.

In this talk I will describe our studies on the effects of the tau protein itself on tau-tau interactions, as well as on tau-cell interactions, with a focus on determining the differences in wild-type (physiological) tau vs phosphorylated, aggregation-prone tau. We have employed several biophysical techniques to study the aggregation propensity of different tau isoforms, with a focus in particular on how phosphorylation effects aggregate formation. From a cellular perspective, we have also been studying tau uptake and find that there are several routes for tau protein to enter the cell, and the multiple extracellular binding partners mediate its internalization through distinct mechanisms. In addition to the differences in uptake behavior, protein properties also alter cellular pathway activation differently, such as pro-inflammatory responses. On-going studies are focused on in vivo studies and identifying potential sites for therapeutic intervention.

Bio: Anne Skaja Robinson became Head of Carnegie Mellon University’s Department of Chemical Engineering in 2018 and Trustee Professor of Chemical Engineering in 2019. Prior to her current appointment, she served as Chair of Chemical and Biomolecular Engineering and Boh Professor of Engineering at Tulane University. She started her academic career at the University of Delaware, where she ultimately became a Full Professor and Associate Chair in Chemical Engineering. Having received both her B.S. and M.S. in Chemical Engineering from Johns Hopkins University, and her Ph.D. in Chemical Engineering from the University of Illinois at Urbana-Champaign, Robinson has earned many honors, including a DuPont Young Professor Award, and a National Science Foundation Presidential Early Career Award for Science and Engineering. She is also a fellow of both the American Institute for Medical and Biological Engineering, and the American Institute of Chemical Engineers. Dr. Robinson’s research focuses on three primary areas of bioengineering: expression and characterization of integral membrane proteins, especially G-protein coupled receptors; understanding and controlling protein aggregation; and cellular mechanisms controlling protein quality and human disease.

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