By utilizing a state-of-the-art algorithm that can identify all superimposed oscillations in an unbiased manner, Dr Zhu's lab discovered a cell-autonomous mammalian 12h-clock that runs independently from the circadian clock to regulate 12h oscillations of gene expression and metabolism (Zhu et al., Cell Metabolism, 2017, Antoulas et al., PloS One, 2018, Zhu et al., JES, 2018). Genes under strong 12h-clock regulation in the liver are enriched in the whole central dogma information flow process (ranging from pre-mRNA splicing, polyadenylation, RNA decay, protein translation, translocation across ER membrane, protein folding and processing in the ER and protein transport from ER to Golgi) in an XBP1s-dependent manner. Cell-autonomous 12h rhythms of gene expression can be entrained by ER and metabolic stress cues in vitro. Intriguingly, the mammalian 12h transcriptome is also highly conserved in marine animals possessing a circatidal clock, therefore implying that mammalian 12h-clock may evolve from the ancient circatidal clock. Dr. Zhu's lab is currently investigating the regulation as well as the physiological/pathological functions of the 12h-clock, with an emphasis on its roles in maintaining hepatic metabolic homeostasis and preventing aging-associated diseases. A combination of state-of-the-art computational, biochemical, genetic, cellular, imaging and genomic approaches is currently utilized in the lab. For a detailed description of the research performed in Zhu lab, please visit http://www.bzhulab.com.
- BS, Peking University, 2006
- PhD, Pennsylvania State University, 2012
- Post-Doctoral Fellow, Baylor College of Medicine, 2017
Education & Training
Meng, H., Gonzalez, N., Lonard, D., Putluri N., Zhu, B., Dacso, C. C., York, B., O'Malley, B. W. XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis. Nature Communications. 2020
Zhu, B. Decoding the function and regulation of the mammalian 12h-clock. Journal of Molecular Cell Biology. 2020; Epub Ahead of Print
Pan, Y., Balance, H., Meng, H., Gonzalez, N., Kim, SM., Abdurehman, L., York, B., Chen, X., Schnytzer, Y., Levy, O., Dacso, C. C., McClung, C. A., O'Malley, B. W., Liu, S., Zhu, B. 12-h clock regulation of genetic information flow by XBP1s. PLoS Biology. 2020; 18(1)
Gao, Y., Chen, L., Han, Y., Wu F., Yang, W., Zhang, Z., Huo, T., Zhu, Y., Yu, C., Kim H., Lee M., Tang, Z., Philips, K., He, B., Jung, S.Y., Song, Y., Zhu, B., Xu, R., Feng, Q. Acetylation of histone H3K27 signals the transcriptional elongation for estrogen receptor alpha. Communications Biology. Communications Biology. 2020; 3(165)
Dasgupta S, Rajapakshe K, Zhu B, Nikolai BC, Yi P, Putluri N, Choi JM, Jung SY, Coarfa C, Westbrook TF, Zhang XH, Foulds CE, Tsai SY, Tsai MJ, O'Malley BW. Glycolytic enzyme PFKFB4 activates oncogenic coactivator SRC-3 to drive breast tumorigenesis and metastasis. Nature. 2018
Zhu B, Zhang Q, Pan Y, Mace EM, York B, Antoulas AC, Dacso CC, O'Malley BW. A cell-autonomous mammalian 12 hr clock coordinates metabolic and stress rhythms. Cell Metabolism. 2017; 25(6): 1305-1319.e9.
Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton R, Butte NF, Moore DD, Chopra AR. Asprosin, a fasting-induced glucogenic protein hormone. Cell. 2016; 165(3): 566-79.
Zhu B, Gates LA, Stashi E, Dagupta S, Gonzalez N, Dean A, Dacso CC, York B, O'Malley BW. Co-activator-dependent oscillation of chromatin accessibility dictates circadian gene amplitude via REV-ERB loading. Molecular Cell. 2015; 60(5): 769-783.
Fleet T, Zheng B, Lin F, Zhu B, Dagupta S, Stashi E, Tackett B, Thevananther S, Rajapkshe K, Gonzalez N, Dean A, Mao J, Malonvannaya A, Qin J, Coarfa C, Demayo F, Dacso CC, Foulds CE, O'Malley BW, York B. SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis. Proceedings of the National Academy of Sciences. 2015; 112(44): E6068-77.
Stashi E, Lanz RB, Mao J, Michailidis G, Zhu B, Kettner N, Putluri N, Reineke EL, Reineke LC, Dasgupta S, Dean A, Stevenson CR, Sivasubramanian N, Sreekumar A, DeMayo F, York B, Loning F, O'Malley BW. SRC-2 is an essential co-activator for orchestrating metabolism and circadian rhythm. Cell Reports. 2014; 6(4): 633-45.
- American Diabetes Association Junior Faculty Development Award, 2018-2022
- UPMC Competitive Medical Research Fund (CMRF) Research Award, 2019-2021
- Pittsburgh Liver Research Center Pilot Research Award, 2020-2021
- NIH Director's New Innovator Award, 2020-2025
