Zhu Lab

Bokai Zhu, PhD
Assistant Professor of Medicine
Division of Endocrinology and Metabolism

The Zhu lab is studying the role of dynamic proteostasis in the regulation of metabolism and aging, with a focus on the 12h ultradian clock.

Zhu Lab

Lab Focus

My laboratory’s interest is in the biology of the 12-hour ultradian clock. In addition to the circadian rhythms (rhythms with a period of ~24h), biological rhythms with a period of ~12h also exist. We recently discovered a cell-autonomous mammalian 12h-clock that runs independently from the circadian clock to regulate 12h oscillations of gene expression and metabolism. We are currently investigating the regulation as well as the physiological/pathological functions of the 12h-clock, using a combination of computational, biochemical, genetic, cellular, imaging and genomic approaches.

What question I’d like to answer

What is the regulation and function of the mammalian 12h clock in age and metabolic related diseases?

For more information: https://www.bzhulab.com/

Faculty Bio

A native of Beijing, China, Bokai received his B.S. degree from Peking University, China and received his Ph.D. at the Pennsylvania State University with Dr. Jeffrey Peters, working on the function of peroxisome proliferator-activated receptor β/δ in skin tumorigenesis. After that, he continued with his post-doctoral training with Dr. Bert W O’Malley at Baylor College of Medicine at Houston, working on the elucidation of regulatory mechanisms and functions of biological rhythms. He was later promoted to the instructor position as a junior faculty at Baylor. During his tenure at Baylor College of Medicine, his research focused on investigating the molecular mechanisms of circadian rhythms regulation and the cross-talk between circadian rhythms and hepatic cellular metabolism. Recently, he uncovered a novel mammalian 12h-clock clock that runs independently from the circadian rhythm to coordinate cellular stress response with metabolism. He joined the Aging Institute at Pittsburgh School of Medicine in September, 2018.

Read more: Department of Medicine Faculty Profile

Selected Publications

Dr. Zhu’s NIH Bibliography

Rinsky M, Weizman E, Ben-Asher HW, Eyal G, Zhu B, Levy O. Temporal gene expression patterns in the coral Euphyllia paradivisa reveal the complexity of biological clocks in the cnidarian-algal symbiosis. Sci Adv. 2022 Sep 16;8(37):eabo6467. doi: 10.1126/sciadv.abo6467. Epub 2022 Sep 16. PMID: 36112690.

Zhu B. Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle. Physiology (Bethesda). 2022 Sep 1;37(5):0. doi: 10.1152/physiol.00003.2022. Epub 2022 Jun 6. PMID: 35658626; PMCID: PMC9394779.

Asher G, Zhu B. Beyond circadian rhythms: emerging roles of ultradian rhythms in control of liver functions. Hepatology. 2022 May 19. doi: 10.1002/hep.32580. Epub ahead of print. PMID: 35591797.

Meng H, Gonzales NM, Jung SY, Lu Y, Putluri N, Zhu B, Dacso CC, Lonard DM, O’Malley BW. Defining the mammalian coactivation of hepatic 12-h clock and lipid metabolism. Cell Rep. 2022 Mar 8;38(10):110491. doi: 10.1016/j.celrep.2022.110491. PMID: 35263593; PMCID: PMC8958721.

Dion W, Ballance H, Lee J, Pan Y, Irfan S, Edwards C, Sun M, Zhang J, Zhang X, Liu S, Zhu B. Four-dimensional nuclear speckle phase separation dynamics regulate proteostasis. Sci Adv. 2022 Jan 7;8(1):eabl4150. doi: 10.1126/sciadv.abl4150. Epub 2022 Jan 5. PMID: 34985945; PMCID: PMC8730402.

Ballance H, Zhu B. Revealing the hidden reality of the mammalian 12-h ultradian rhythms. Cell Mol Life Sci. 2021 Apr;78(7):3127-3140. doi: 10.1007/s00018-020-03730-5. Epub 2021 Jan 15. PMID: 33449146; PMCID: PMC8407301.

Meng H, Gonzales NM, Lonard DM, Putluri N, Zhu B, Dacso CC, York B, O’Malley BW. XBP1 links the 12-hour clock to NAFLD and regulation of membrane fluidity and lipid homeostasis. Nat Commun. 2020 Dec 4;11(1):6215. doi: 10.1038/s41467-020-20028-z. PMID: 33277471; PMCID: PMC7718229.

Pan Y, Ballance H, Meng H, Gonzalez N, Kim SM, Abdurehman L, York B, Chen X, Schnytzer Y, Levy O, Dacso CC, McClung CA, O’Malley BW, Liu S, Zhu B. 12-h clock regulation of genetic information flow by XBP1s. PLoS Biol. 2020 Jan 14;18(1):e3000580. doi: 10.1371/journal.pbio.3000580. PMID: 31935211; PMCID: PMC6959563.

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 Metab. 2017 Jun 6;25(6):1305-1319.e9. doi: 10.1016/j.cmet.2017.05.004. PMID: 28591634; PMCID: PMC5526350.

Zhu B, Gates LA, Stashi E, Dasgupta S, Gonzales N, Dean A, Dacso CC, York B, O’Malley BW. Coactivator-Dependent Oscillation of Chromatin Accessibility Dictates Circadian Gene Amplitude via REV-ERB Loading. Mol Cell. 2015 Dec 3;60(5):769-783. doi: 10.1016/j.molcel.2015.10.024. Epub 2015 Nov 21. PMID: 26611104; PMCID: PMC4671835.

Current Lab Members

William Dion, Graduate Student
Syeda Kubra, Postdoctoral Associate
Aishwarya Ponna, Undergraduate Student
Michelle Sun, Research Specialist
Daniella Santucci, Undergraduate Student

Megan Ye, BS, Laboratory Research Technician
Bugra Zengin, MD, Visiting Scholar

Research Support