Medical Engineering Distinguished Seminar, Amy Herr

Oncoprotein isoforms and fragments are implicated in cancer drug resistance mechanisms. HER2 and Estrogen Receptor (ER) proteoforms are two important examples in breast cancer. While proteoforms are of substantial interest, the immunoassay reigns as the de facto standard for direct measurement of protein targets in single cells (i.e., flow cytometry, mass cytometry/CyTOF, immunofluorescence). Yet, immunoassays typically lack the selectivity needed to distinguish proteoforms.

To bridge this gap, we have introduced a suite of ‘electrophoretic cytometry' tools – built on microfluidic principles – designed to increase target selectivity beyond simple immunoassays using immunoblot assay designs. Enhanced selectivity is essential for targets that lack high quality immunoreagents – as is the case for the vast majority of proteoforms. Immunoblots concatenate an upstream electrophoretic separation (equilibrium or non-equilibrium) to a downstream immunoassay to report two physicochemical properties for the targets of interest.

In fundamental engineering and design, I will discuss how the physics and chemistry accessible in microsystems allows both the "scale-down" of immunoblotting to single cells and the "scale-up" to concurrent analyses of large numbers of cells. Precision control of fluids and materials transport (primarily diffusion-driven) integrates sophisticated sample preparation – the unsung hero of measurement science.

I will illustrate the power of precision, sensitive assays using case studies of single cancer-cell analysis to show how microfluidic design strategies seamlessly integrate sample preparation and handling steps with quantitative bioanalytical assays in a compact format. Through a handful of examples, I will share how precision molecular measurement capabilities are advancing detection of not just presence/absence of protein targets, but more refined understanding of the expression stoichiometry of proteoforms of interest.

Taken together, we view microfluidic design strategies as key to advancing protein measurement performance needed to address unmet gaps in quantitative biology and precision medicine.

Biography: Amy E. Herr received a BS degree in Engineering & Applied Science from the California Institute of Technology and MS and PhD degrees in Mechanical Engineering from Stanford University, where she was an NSF Graduate Research Fellow. She is currently Professor of Bioengineering at the University of California, Berkeley and a Chan Zuckerberg Biohub Investigator. Until 2020, she held a 5-year appointment as the Lester John & Lynne Dewar Lloyd Distinguished Professor. Prior to joining UC Berkeley, she was a staff member in the Biosystems Research Group at Sandia National Laboratories (Livermore, CA). Her research interests include bioinstrumentation innovation to advance quantitation in the biosciences & biomedicine, in particular the study and application of electrokinetic phenomena in single-cell and sub-cellular analyses. Her pedagogical interests are in bioengineering design and transport. Professor Herr is an elected Fellow of the American Institute of Medical and Biological Engineering (AIMBE) and an elected member of the National Academy of Inventors (2017). She serves on the National Advisory Board for Biomedical Imaging and Bioengineering at NIH (NIBIB; 2020-23) and for the US Defense Advanced Research Projects Agency (DARPA) Biotechnology Office (BTO; 2020-23). She has served as a standing member of the NIH Nanotechnology Study Section (2013-2019) and was one of 13 US faculty appointed to the DARPA's Defense Sciences Study Group (DSSG; 2018-2019). Professor Herr is Vice President of the Board of the Chemical & Biological Microsystems Society (CBMS; which oversees the microTAS conferences), and has served as Co-Chair of the 2020 EMBL Microfluidics Conference, Co-Chair of the 2021 International Conference on Miniaturized Systems for Chemistry & Life Sciences (microTAS), and Chaired (2009) and Vicechaired (2007) the Gordon Research Conference (GRC) on the Physics & Chemistry of Microfluidics. Professor Herr was CoDirector of the Cold Spring Harbor Laboratory's Single Cell Analysis summer course (2015, 2016), and is an Instructor in that course (2015-2021). At UC Berkeley, she serves as Faculty Director of both the Bakar Fellows Program (2016-present) and the Bakar BioEnginuity Hub for the Vice Chancellor for Research. She was the Department of Bioengineering's ViceChair for Engineering Engagement (2016-2020). She has been recognized as a: Sciex Microscale Separations Innovation Medalist (2018), Visionary Awardee by the City of Berkeley (2017; one of three), Chan Zuckerberg Biohub Investigator (2017-2022), 2016 Mid-Career Achievement Award from the American Electrophoresis Society (AES), 2015 Georges Guiochon Faculty Fellow from HPLC (inaugural), 2012 Young Innovator Award from Analytical Chemistry/CBMS, 2011 NSF CAREER award, 2010 NIH New Innovator Award, 2010 Alfred P. Sloan Research Fellowship in chemistry, 2010 New Investigator Award in Analytical Chemistry from Eli Lilly & Co., 2009 Defense Advanced Research Projects Agency (DARPA) Young Faculty Award, 2009 Hellman Family Faculty Fund Award from UC Berkeley, 2008 Regents' Junior Faculty Fellowship from the University of California, and held the Mary Shepard B. Upson Visiting Professorship at Cornell University. To support the international technical community, she actively serves on the technical organizing committees of international conferences and created the Women in Microfluidics list to aid other conference organizers in highlighting stellar female researchers from around the globe (microfluidics.berkeley.edu). In teaching and mentoring, Professor Herr has been honored as the 2019 Outstanding Postdoctoral Advisor Award from UC Berkeley, the 2012 Ellen Weaver Award from the Association for Women in Science (AWIS), the 2012 Outstanding Instructor Award in Bioengineering (Bioengineering Honor Society student vote) and a 2007 Outstanding Mentor Award from Sandia National Laboratories. She is faculty advisor to the UC Berkeley chapter of the Society of Women Engineers (SWE) and the Graduate Women in Engineering (GWE), as well as assisted with establishing the UC Berkeley chapter of the National Science Policy Group (NSPG). https://herrlab.berkeley.edu/