Liu Lab

Yuan Liu, PhD
Assistant Professor
Division of Pulmonary, Allergy, and Critical Care Medicine

Our lab is interested in small molecule therapeutic development targeting ubiquitin-dependent protein degradation in age-related diseases.

yul119@pitt.edu

Yuan Liu Lab

Lab Focus

Our laboratory focuses on understanding the regulation of proteostasis through the ubiquitin-proteasome and autophagy-lysosome systems. By targeting proteins with critical biological activities, including AMPK, TFEB, and PINK1, we have identified E3 ubiquitin ligases that modulate their protein stability through high throughput siRNA screening and proteomic analysis. We have also developed small molecule inhibitors that interfere with the ubiquitin-dependent protein degradation and prolong the protein half-life of these critical protein targets. These novel compounds have proven effective in various age-related animal models including metabolic disorder (NAFLD), neurodegeneration (PD) and dry AMD. As a joint effort with Toren Finkel, MD, PhD and Bill Chen, PhD, we are currently developing small molecule AMPK and TFEB potentiators for clinical trials.

What question I’d like to answer

Can we start a new era for small molecule therapeutics that target complex diseases by regulating protein networks?

Faculty Bio

Yuan received her master’s degree in Genetics and her PhD from Nagoya University. After completing her postdoctoral training at the California Institute of Technology, Yuan joined the faculty at the University of Pittsburgh, in the Division of Pulmonary, Allergy and Critical Care Medicine (PACCM) in 2015. She joined the Aging Institute in 2018. Yuan serves on multiple editorial boards and grant review study sessions. Yuan is the co-founder of pharmaceutical startup company Generian.

Selected Publications

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. Am J Physiol Cell Physiol. 2017 Nov 1;313(5):C584-C592. doi: 10.1152/ajpcell.00193.2017. Epub 2017 Oct 4. Erratum in: Am J Physiol Cell Physiol. 2019 Apr 1;316(4):C582. PMID: 28978524; PMCID: PMC5792167. (Corresponding author)

Liu Y, Lear TB, 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):e131834. doi: 10.1172/jci.insight.131834. PMID: 32493843; PMCID: PMC7308049.

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 Biol. 2020 May;32:101485. doi: 10.1016/j.redox.2020.101485. Epub 2020 Mar 4. PMID: 32171724; PMCID: PMC7068124. (Co-Corresponding author)

Liu Y, Jurczak MJ, Lear TB, 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 pAMPKα degradation and ameliorates insulin resistance. Nat Chem Biol. 2021 Mar;17(3):298-306. doi: 10.1038/s41589-020-00723-0. Epub 2021 Jan 25. PMID: 33495648. (Co-Corresponding author)

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. Nat Commun. 2021 Jun 23;12(1):3907. doi: 10.1038/s41467-021-24156-y. PMID: 34162861; PMCID: PMC8222394. (Co-Corresponding author)

Current Lab Members

Qing Cao, Graduate Student
Daniel Camarco, Research Associate