by focusing on how timekeeping mechanisms and nuclear condensates work together to maintain protein homeostasis.
by focusing on how timekeeping mechanisms and nuclear condensates work together to maintain protein homeostasis.
Proteins are the building blocks of life, but keeping them healthy is a constant challenge for cells. The system that manages protein folding, repair, and clearance—called proteostasis—breaks down as we age, and this decline is a major driver of neurodegenerative diseases like Alzheimer’s.
In our lab, we recently discovered something surprising: proteostasis doesn’t run at a constant level, but instead follows a 12-hour rhythm, controlled by a unique biological clock that is separate from the circadian (24-hour) clock. This mammalian 12-hour oscillator helps cells anticipate stress and maintain balance in their protein environment.
Even more exciting, our newest research shows that nuclear speckles—liquid-like compartments inside the nucleus—play a central role in this process. We’ve found that nuclear speckles act as sensors of protein stress and can even be rejuvenated to restore protein health. By “resetting” these structures, we’ve been able to improve proteostasis and reduce toxic protein buildup in models of tauopathy, a devastating neurodegenerative disease.
For a brief introduction of our research, please check out the following videos and news coverage of our work.
4 minutes short video of our work
Bokai Zhu, Ph.D.
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. After that, he continued with his post-doctoral training with Dr. Bert W O’Malley at Baylor College of Medicine at Houston. 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 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.
Selective Honors
A postdoctoral position is currently available. Start date is immediate and flexible. Candidates should ideally have received a doctoral degree no more than 3 years before the start date. Researchers with a passion in systemic and quantitative chronobiology, cell biology, metabolism and endocrinology, molecular biology, gene regulation and epigenetics are welcome to apply.
Graduate Student
Dr. Zhu is affiliated with Integrative Systems Biology (ISB), Cell Biology and Molecular Physiology (CBMP), Molecular Genetics and Development Biology (MGDB), and joint CMU-Pitt Program in Computational Biology (CPCB) graduate programs. Several rotation projects are currently available for prospective students.
Research Technician(s)
Please apply here.
Please email your application to Bokai, including:
A cover letter describing your past training, research interests and career goals (optional)
A detailed CV
Contact information of three referees
Room 565, Bridgeside Point 1, 100 Technology Dr, Pittsburgh, PA, 15219
Email: BZHU@pitt.edu Phone:412-383-0447
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