Dr. Chen’s primary research interest includes the study of the molecular mechanisms that control inflammation and cell proliferation via protein ubiquitination. . Specifically, over the last five years, his lab have successfully cloned over 300 novel ubiquitin E3 ligases, of which he has subsequently determined many substrates. These works have been published in top-tier journals related to protein ubiquitination—including Nature Immunology, Nature Medicine, Cell Reports and Science Translational Medicine, Journal of Experimental Medicine and JCI. His second area of research interest is small molecule drug design. In the past three years, he has submitted 10 provisional patents related to novel anti-inflammatory and autophagy activating compounds. In addition, he have successfully designed and synthesized a novel series of first-in-class small molecule FBXO3 protein inhibitors. One of his lead compounds, BC-1261, has passed preclinical PK/toxicity studies and was approved for IND in February 2019. This compound is currently on track for a Phase I trial in November 2019. Recently, he has also designed a novel series of potent, selective PDE4, HECTD2, StamBP, Fbxo7, Fbxo48, FIEL1, DCAF7 inhibitors that exhibit excellent activities in vivo. His long-term goal is to develop a new class of therapeutics that combat inflammatory diseases by focusing on novel mechanisms. Please visit (http://www.drugdiscoverycenter.org/) for Dr. Chen’s detailed work.
- BS, Chemistry, Wuhan University, 2003
- PhD, Biochemistry, University of Iowa, 2008
- Post-doctoral Fellow, University of Iowa, 2009
Education & Training
Lear TB, McKelvey AC, Evankovich J, Rajbhandari S, Coon TA, Dunn SR, Londino JD, McVerry BJ, Zhang Y, Valenzi E, Burton C, Gordon R, Gingras S, Lockwood K, Jurczak MJ, Lafyatis R, Shlomchik MJ, Liu Y, Chen BB. Kiaa0317 regulates pulmonary inflammation through socs2 degradation. JCI Insight. 2019; in press
Evankovich J, Lear T, Baldwin C, Chen Y, White V, Villandre J, Londino J, Liu Y, McVerry B, Kitsios GD, Mallampalli RK, Chen BB. Toll-Like Receptor 8 Stability is Regulated by Ring Finger 216 in response to circulating MicroRNAs. Am J Respir Cell Mol Biol. 2019; Aug 6: doi:10.1165/rcmb.2018-0373OC.
Evankovich, J, Lear, T, McKelvey, A, Dunn, S, Londino, J, Liu, Y, Chen, BB, Mallampalli, RK. Receptor for Advanced Glycation End Products is Targeted by Fbxo10 for Ubiquitination and Degradation. FASEB J. 2017; Sep;31(9): 3894-3903.
Bednash, JS, Weathington, NM, Londino, J, Rojas, M, Gulick, DL, Fort, R, Han, S, McKelvey, AC, Chen, BB, Mallampalli, RK. Therapeutic Targeting of the Deubiquitinase STAMBP Reduces Inflammation by Destabilizing the NALP7 Inflammasome. Nature Communication. 2017; 8: 15203.
McKelvey, AC, Lear, T, Dunn, SR, Evankovich, J, Londino, JD, Bednash, JS, Zhang, Y, McVerry, BJ, Liu, Y, Chen, BB. RING Finger E3 Ligase PPP1R11 Regulates TLR2 Signaling and Innate Immunity. eLife. 2016; Nov2;5: e18496.
Lear T, McKelvey AC, Rajbhandari S, Coon TA, Connelly W, Zhao J, Dunn SR, Liu Y, Zhang Y, Kass DJ, Chen BB. Ubiquitin E3 Ligase FIEL1 Regulates Fibrotic Lung Injury through SUMO-E3 Ligase PIAS4. J Exp Med. 2016; May 30;213(6): 1029-46.
Zou, C, Li, J, Xiong, S, Chen, Y, Wu, Q, Weathington, NM, Han, SY, Snavely, C, Chen, BB, Mallampalli, RK. Mortality factor 4 like 1 (Morf4l1) protein mediates epithelial cell death in experimental pneumonia. Sci Trans Med. 2015; Oct 28;7(311): 311ra171.
Coon, TA, McKelvey, AC, Lear, T, Rajbhandari, S, Dunn, RS, Connelly, W, Zhao, J, Han, S, Liu, Y, McVerry, BJ, Zhang, Y, Chen, BB. The proinflammatory role of HECTD2 in innate immunity and experimental lung injury. Sci Trans Med. 2015; Jul8;7(295): 295ra109.
Coon, TA, McKelvey, AC, Weathington, NM, Birru, RL, Lear, T, Leikauf, GD, Chen, BB. Novel PDE4 Inhibitors Derived From Chinese Medicine Forsythia. PLOS ONE. 2014; Dec 30;9(12): e115937.
Chen, BB, Coon, TA, Glasser, JR, Zou, C, Ellis, B, Das, T, McKelvey, AC, Rajbhandari, S, Lear, T, Kamga, C, Shiva, S, Li, C, Pilewski, JM, Callio, J, Chu, CT, Ray, A, Ray, P, Tyurina, YY, Kagan, VE, Mallampalli, RK. E3 ligase subunit Fbxo15 and PINK1 kinase regulate cardiolipin synthase 1 stability and mitochondrial function in pneumonia. Cell Reports. 2014; Apr 24; 7(2): 476-87.
- Pittsburgh International Lung Conference Peer Award, 2012
- Pitt Innovator Award, 2014
- Munich/Pittsburgh International Lung Conference Investigator Award, 2015
- NHLBI Emerging Investigator Award (R35), 2018
- University of Pittsburgh PACCM Outstanding Mentor Award, 2019
Title: Hemostasis and Vascular Biology Research Institute - Chen
Role: Co-Investigator
Funding Agency: Institute for Transfusion Medicine
Start Year: 2013
End Year: 2028
