Bokai Zhu, Ph.D.

  • Assistant Professor
  • Department of Medicine
  • Division of Endocrinology and Metabolism, Aging Institute of UPMC

Education & Training

  • Ph.D.-Molecular Medicine Program, Penn State University, University Park, PA, 2012
  • B.S.-Biology, Peking University, China, 2006

Research Interest Summary

We are investigated the regulation and function of 12hr (circatidal) clock using mouse liver as a major organ.

Research Categories

Research Interests

Unveiling "Musica universalis" of the Cell: A Brief History of biological 12h Rhythms: Musica Universalis is an ancient philosophical concept that claims the movements of celestial bodies follow mathematical equations and resonate to produce an inaudible harmony of music, and the harmonious sounds that men make were mere an approximation of this larger harmony of the universe. Besides music, electromagnetic waves such as light and electronic signals also are presented as harmonic resonances. Despite the seemingly universal theme of harmonic resonance in various disciplines, it was not until very recently that the same harmonic resonance was discovered to also exist in biological systems. Intriguingly, contrary to the traditional belief that biological system is either at constant homeostasis (not rhythmic) or cycling with a single frequency, it is now appreciated that most biological systems have no homeostatic “set point”, but rather oscillate as composite rhythms consisting of a series of superimposed oscillations. These oscillations often cycle at different harmonics of the circadian rhythm (~24h), and among them the ~12h oscillations are found very prevalent. My lab is studying these 12h oscillations, with special interest in their evolutionary origin, regulation and functions in mammals, as well as their relationship with the 24h circadian rhythm.

Representative Publications

Antoulas, A.C., Zhu, B., Zhang, Q., York, B., O'Malley, B.W. and Dacso, C.C. A novel mathematical method for disclosing oscillations in gene transcription: a comparative study. PloS One (2018); 13(9): e0198503

Zhu, B., Dacso, C.C. and O'Malley, B.W. Unveiling “Musica Universalis” of the Cell: A brief history of biological 12h rhythms. Journal of Endocrine Society (2018); 2(7):727-752. DOI: 10.1210/js.2018-00113

Dasgupta, S., Rajapakshe, K., Zhu, B., Nikolai B.C., Yi, P., Putluri, N., Choi, J.M., Jung, S.Y., Coarfa, C., Westbrook, T.F., Zhang, X.H., Foulds, C.E., Tsai, S.Y., Tsai, M.J. and O’Malley, B.W. Glycolytic enzyme PFKFB4 activates oncogenic coactivator SRC-3 to drive breast tumorigenesis and metastasis. Nature (2018). DOI: 10.1038/s41586-018-0018-1

Gates, L.A., Shi, J., Rohira, A.D., Feng, Q., Zhu, B., Bedford, M.T., Sagum, C.A., Jung, S.Y., Qin, J., Tsai, M., Tsai, S.Y., Li, W., Foulds, C.E. and O’Malley, B.W. Acetylation on histone H3 lysine 9 mediates a switch from transcription initiation to elongation. Journal of Biological Chemistry (2017). DOI: 10.1074/jbc.M117.802074 

Zhu, B., Zhang, Q., Pan, Y., Mace, E.M., York, B., Antoulas, A.C., Dacso, C.C. and O'Malley, B.W. A cell-autonomous mammalian 12 hr clock coordinates metabolic and stress rhythms. Cell Metabolism (2017). 25(6):1305-1319.e9. DOI: 10.1016/j.cmet.2017.05.004 [Featured in “editors’ choice” highlight in the issue of Science :30 Jun 2017:]

[Featured in “editors’ choice” highlight in the issue of Science Translational Medicine :28 Jun 2017:]  

[Featured in the Scientist magazine:

Romere, C., Duerrschmid, C., Bournat, J., Constable, P., Jain, M., Xia, F., Saha, P.K., Del Solar, M., Zhu, B., York, B., Sarkar, P., Rendon, D.A., Gaber, M.W., LeMaire, S.A., Coselli, J.S., Milewicz, D.M., Sutton, R., Butte, N.F., Moore, D.D. and Chopra, A.R. Asprosin, a fasting-induced glucogenic protein hormone. Cell (2016). DOI: 10.1016/j.cell.2016.02.063   

Zhu, B., Gates, L.A., Stashi, E., Dagupta, S., Gonzalez, N., Dean, A., Dasco, C.C., York, B. and O’Malley, B.W. Co-activator-dependent oscillation of chromatin accessibility dictates circadian gene amplitude via REV-ERB loading. Molecular Cell (2015) Nov 20. DOI: 10.1016/j.molcel.2015.10.024

Fleet, T., Zheng, B., Lin, F., Zhu, B., Dagupta, S., Stashi, E., Tackett, B., Thevananther, S., Rajapakshe, K., Gonzalez, N., Dean, A., Mao, J., Malonvannaya, A., Qin, J., Coarfa, C., Demayo, F., Dasco, C.C., Foulds, C.E., O’Malley, B.W. and York, B. SRC-2 orchestrates polygenic inputs for fine-tuning glucose homeostasis. Proceedings of the National Academy of Sciences (2015) Oct 20. DOI: 10.1073/pnas.1519073112

Zhu, B., Ferry, C.H., Markell, L.M., Blazanin, N., Glick, A.B., Gonzalez, F.J. and Peters, J.M. The nuclear receptor PPARβ/δ promotes oncogene-induced cellular senescence through repression of endoplasmic reticulum stress. Journal of Biological Chemistry (2014) Jul 18;289(29):20102-19

Stashi, E., Lanz, R.B., Mao, J., Michailidis, G.., Zhu, B., Kettner, N., Putluri, N., Reineke, E.L., Reineke, L.C., Dasgupta, S., Dean, A., Stevenson, C.R., Sivasubramanian, N., Sreekumar, A., DeMayo, F., York, B., Loning, F. and O’Malley, B.W. SRC-2 is an essential co-activator for orchestrating metabolism and circadian rhythm. Cell Reports (2014) 6 (4): 633-645  

Full List of Publications

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