Research Assistant Professor of Biomedical Engineering
Education
Biography
Dr. Longwei Liu is an Assistant Professor of Research at the Alfred E. Mann Department of Biomedical Engineering at USC Viterbi School of Engineering. My long-term research career goal is to develop tools to understand better how intracellular signaling mediates intercellular communications, with a specific interest in immune-tumor cell interactions. The current research focus of Dr. Liu is to develop tools to better understand and control intracellular signaling, with a specific interest in immune-tumor cell interactions. Specifically, he develops genetically-encoded biosensors based on FRET or single fluorescent protein using a directed evolution approach and apply these biosensors to visualize molecular signals in live cells with high spatiotemporal resolution. With the guidance of these new signaling insights, he also develop novel controllable CAR-T cells for efficient immune therapy targeting solid tumors. Dr. Liu obtained his PhD degree in Biomedical Engineering from Tsinghua University in 2018 and completed his postdoctoral training at the University of California, San Diego (UCSD) in 2022. Dr. Liu is the recipient of NIH K01 award, USC 2023 MHIRA award et.al.
Dr. Liu has published eight first-author papers in Nature Materials (2017), PNAS (2020), The FASEB J (2021), Nature Communications (2021), ACS Central Science (2023) et al., three co-corresponding papers in ACS Sensors (2021), EBMO J (2022), and Clin Transl Med (2022), as well as >10 co-author papers in Nature Reviews Bioengineering (2023), Nature Materials (2022), Biomaterials (2016, 2017) et al.
Research Summary
My training encompasses an interdisciplinary education and specialized training in areas of tissue engineering, cellular and molecular biology, and bioengineering, equipping me with the necessary breadth and depth of knowledge. In 2017, I made a pivotal discovery regarding the interaction between migratory liver endothelial cells and Hepatic stellate cells (HSCs) during early-stage fibrosis. By creating stage-mimicking in vitro fibrotic microinches (FμN) and in vivo mouse fibrosis models, my work reveals stage-specific angiogenesis-induced liver fibrogenesis via a previously uncharted mechanotransduction mechanism. Specifically, I discovered, for the first time, that migratory liver endothelial cells could directly activate Hepatic stellate cells (HSCs) through mechanotransduction via condensed collagen fibers in early-stage but not late-stage fibrosis, which offered precise intervention strategies targeting stage-specific disease progression and was verified in mouse models (Nature Materials, 2017, first author). This research has also been highlighted in Nature Materials 16, 1176–1177(2017), Nature Reviews Gastroenterology & Hepatology 15, 6 (2018), and Hepatology 69: 449-451(2019). Later, taking advantage of my expertise in genetic engineering as well as AFM-based manipulation of single cells, I systematically investigated the mechanical force-mediated myofibroblast–fibroblast crosstalk via the fibrous matrix, which we termed paratensile signaling. Such paratensile signaling enables instantaneous and long-range mechanotransduction via collagen fibers (less than 1 s and over 70 μm) to activate a single fibroblast, which is intracellularly mediated by DDR2 and integrin signaling pathways in a calcium-dependent manner (PNAS, 2020, first author). I further identified asporin, an ECM protein that may function as a collagen modulator to negatively modulate paratensile signaling as a mechanism to promote keloid (skin fibrosis) progression (The FASEB J.2021, first author).
My past postdoc training mainly focuses on using biosensors to understand complex cellular processes. With Dr. Wang, I established an approach integrating high-throughput FRET sorting and next-generation sequencing (FRET-Seq) to directly identify sensitive biosensors from large-scale libraries in mammalian cells, utilizing the novel design of self-activating FRET (saFRET) biosensor. So far, I have developed and optimized the FRET biosensors for Fyn and ZAP70 kinases that exhibit enhanced performance and enable the dynamic imaging of T-cell activation. By using the optimized ZAP70 saFRET biosensor as screening tool, I also identified an FDA-approved drug, sunitinib, that can be repurposed to inhibit ZAP70 activity and autoimmune-disease-related T-cell activation (Nature Communications, 2021, first author) and led to 2 U.S. patent applications. To facilitate the broader usage of this method, I posted a detailed protocol for this platform (Protocol Exchange 2021, first author). Throughout this research journey, I have compiled a comprehensive review of the current applications and limitations of FRET biosensors as well as envisioned future improvements for FRET biosensors (Frontiers in Bioengineering and Biotechnology, 2020, first author). Additionally, by collaborating with Dr. Shu Chien and Dr. Michael Berns's lab, we used FRET-biosensors to investigate the dynamic modes of Piezo1-mediated signaling and revealed a bimodal pattern of Piezo1-induced intracellular calcium signaling and its regulatory mechanisms (The EMBO Journal, 2022, co-corresponding author). Together with a master student, we developed a FRET biosensor capable of visualizing the dynamic H3K27me3 in single live cell during cancer cell development (ACS Sensors, 2021, co-corresponding author). Recently, I also systematic reviewed the current progress on CAR-T cell engineering for solid tumors (Clinical and Translational Medicine, 2022, corresponding author), remote control of CAR-T cells (Nature Reviews Bioengineering, 2023, second author) and advanced imaging tools for the imaging of T cells (Advanced Drug Delivery Reviews, 2023, under review, corresponding author).
Though I don’t have teaching obligations, I have gathered teaching experiences by serving as a guest lecturer for SCRM 525 (Tools and Techniques in Stem Cell Biology, USC, fall 2023), BE-230A Biochemistry (UCSD, fall 2022) and as a teaching assistant for Tissue Engineering (THU, 2 quarters) and Introduction to Biomedical Engineering (THU, 1 quarter).
