The ubiquitin proteasome system (UPS) is a complex, hierarchical, and regulated cellular system that dominates selective protein degradation to modulate the abundance and activity of proteins in the cell. The majority of mammalian proteins are controlled by the UPS through the ATP-dependent enzymatic cascade, including the ubiquitin activating enzyme (E1), the ubiquitin conjugating enzyme (E2), and the ubiquitin ligase (E3). Dr. Liu has a long-standing research interest in UPS, especially ubiquitin ligase E3s. Liu Laboratory focuses on understanding the regulatory mechanisms of ubiquitin-mediated protein degradation and developing small molecule therapeutics to treat lung inflammatory injury and age-associated disorders. Through targeting the ubiquitin E3s, Dr. Liu has developed a series of small molecule activators of AMPK, TFEB, NAMPT to boost metabolism, autophagy, and NAD+ production, respectively, which proves potent in animals. These projects and new chemical entities have been licensed to biopharmaceutical companies for commercial development to treat age-related diseases and they are currently ready for clinical trials. The ongoing projects mainly concentrate on developing small molecule transcription factor degraders to treat malignancies.
- MS, Huazhong University of Science and Technology, 2007
- PhD, Nagoya University, 2010
Education & Training
Liu, Y., Lear, T., Iannone, O., Shiva, S., Corey, C., Rajbhandari, S., Jerome, J., Chen, BB., Mallampalli, RK. The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin. Journal of Biological Chemistry. 2015; May 8;290(19): 11843-52.
Lear, T., Dunn, SR., McKelvey, AC., Mir, A., Evankovich, J., Chen, BB., Liu, Y. RING finger protein 113A Regulates C-X-C Chemokine Receptor Type 4 Stability and Signaling. American Journal of Physiology-Cell Physiology. 2017; Nov 1;313(5): C584-C592.
Tong, Y., Lear, TB., Evankovich, J., Chen, Y., Londino, JD., Myerburg, MM., Zhang, Y., Popescu, ID., McDyer, JF., McVerry, BJ., Lockwood, KC., Jurczak, MJ, Liu, Y., Chen, BB. The RNFT2/IL-3Ra axis regulates IL-3 signaling and innate immunity. JCI Insight. 2020; Feb 13;5(3)
Chen, Y., Evankovich, JW., Lear, TB., Tuncer, F., Kennerdell, JR., Camarco, DP., Shishido, MS., Liu, Y., Chen, BB. A small molecule NRF2 activator BC-1901S ameliorates inflammation through DCAF1/NRF2 axis. Redox Biology. 2020; May;32:101485
Liu, Y., Lear, T., Verma, M., Wang, KZ., Otero, PA., McKelvey, AC., Dunn, SR., Steer, E., Bateman, NW., Wu, C., Jiang, Y., Weathington, NM., Rojas, M., Chu, CT., Chen, BB., Mallampalli, RK. Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1. JCI Insight. 2020; Jun 4;5(11)
Liu, Y., Jurczak, MJ., Lear, T., Lin, B., Larsen, MB., Kennerdell, JR., Chen, Y., Huckestein, BR., Nguyen, MK., Tuncer, F., Jiang, Y., Monga, SP., O’Donnell, CP., Finkel, T., Chen, BB., Mallampalli, RK. A Fbxo48 inhibitor prevents pAMPKa degradation and ameliorates insulin resistance. Nature Chemical Biology. 2021; Mar;17(3): 298-306.
Chen, Y., Lear, TB., Evankovich, JW., Larsen, MB., Lin, B., Alfaras, I., Kennerdell, JR., Salminen, L., Camarco, DP., Lockwood, KC., Tuncer, F., Liu, J., Myerburg, MM., McDyer, JF., Liu, Y., Finkel, T., Chen, BB. A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry. Nature Communications. 2021; Jun 23;12(1): 3907.
Lear, TB., Chen, BB., Liu, Y. COVID-19 Therapeutics: Challenges and Opportunities. Lung Biology and Pathophysiology (1st ed.). 2024; Chapter 11. Zhao, Y. (Ed.). CRC Press.
- Patent: Novel anti-neoplastic and anti-inflammatory DCN1 inhibitor (US 62/300,451)
- Patent: Composition and methods for treating cancer and inflammatory diseases (US 62/325,842)
- Patent: Small molecule Ampk activators (US 62/404,592)
- Patent: Chemical inhibition of the E3 Ligase subunit Fbxo7 confers neuroprotection and anti-inflammatory activity by stabilizing mitochondria (US 62/527,492)
- PITT Innovator Award, 2019
- PITT Innovator Award, 2023
