Department of Biological Sciences
601A Mellon Institute
Education & Professional Experience
Ph.D.: McGill University
Assistant Professor, Carnegie Mellon University
Postdoctoral Fellow, Dartmouth College
Postdoctoral Fellow, Princeton University
Postdoctoral Fellow, University of Pennsylvania
The phase transition process of liquid-liquid demixing organizes proteins and RNAs into liquid compartments in cells. We study how this process promotes cellular functions in healthy cells and how misregulation of it leads to cancer. Building on this, we engineer synthetic organelles by taking inspiration from cells and develop therapeutic strategies by targeting phase transition in cancer cells.
Investigate functional significance of phase transition in cells
We developed optogenetic tools to manipulate phase transition in live cells so we could observe the functional consequences. We focus on telomere DNA synthesis in cancer cells, a biochemical reaction that all cancer cells rely on for immortality. We demonstrated that condensation of liquid droplets on telomeres of telomerase-free cancer cells clusters telomeres to provide templates required for homology-directed DNA synthesis. We ask how the nucleation process is regulated, how the components are recruited , how the material properties are controlled and how they contribute to telomere DNA synthesis and cancer cell growth.
Engineer synthetic organelles
Using a bottom-up approach to construct liquid organelles will advance our understanding of liquid condensation in cells and inspire new applications exploiting phase transition. With advanced biophysical characterizations such as microrheologyand fluorescence correlation spectroscopy, we investigate how the material properties and chemical composition of liquid organelles are defined and how they affect biochemistry within.
Control phase transition for cancer therapy
We demonstrated that liquid condensation contributes to telomere elongation in telomerase-free cancer cells by clustering telomeres to provide templates required for homology-directed telomere DNA synthesis which cancer cells rely on for immortality. We set out to develop cancer therapies to inhibit telomere synthesis by combining experimental and theoretical approaches to manipulate phase behavior.
R. Zhao, D. M. Chenoweth, H. Zhang, Chemical dimerization-induced protein condensates on telomeres, Journal of Visualized Experiments, e62173 (2021)
G-Y Chen, F Renda, H. Zhang, A. Gokden, D. Z. Wu, D. M. Chenoweth, A. Khodjakov, M. A. Lampson, Tension promotes kinetochore-microtubule release by Aurora B kinase, Journal of Cell Biology (2021)
Huaiying Zhang, The glassiness of hardening protein droplets, Science (2020)
Huaiying Zhang, Rongwei Zhao, Jason Tones, Michel Liu, Robert Dilley, David M. Chenoweth, Roger A. Greenberg, and Michael A. Lampson, Nuclear body phase separation drives telomere clustering in ALT cancer cells, Molecular Biology of the Cell (2020)
Reversible control of protein localization in living cells using a photocaged-photocleavable chemical dimerizer, Journal of the American Chemical Society (2018)
H. Zhang, D. M. Chenoweth, and M. A. Lampson, Optogenetic control of mitosis with photocagedchemical dimerizers, Methods in Cell Biology – Mitosis & Meiosis (2018)
H. Zhang*, C. Aonbangkhen*, E Tarasovetc, E. R. Ballister, D. M. Chenoweth, M. A. Lampson. (*equal contribution), Optogenetic control of kinetochore function, Nature Chemical Biology (2017)
N. Taylor, S. Elbaum-Garfinkle, N. Vaidya, H. Zhang, H. A. Stone, C. P. Brangwynne, Biophysical characterization of organelle-based RNA/protein liquid phases using microfluidics, Soft Matter (2016)
H. Zhang, S. Elbaum-Garfinkle, E. M. Langdon, N. Taylor, P. Occhipinti, A. A. Bridges, C. P. Brangwynne, and A. S. Gladfelter, RNA controls polyQ protein phase transitions, Molecular Cell (2015)
Y. Wu, H. Zhang, E. E. Grifin, Coupling between cytoplasmic concentration gradients through local control of protein mobility in the Caenorhabditis elegans zygote, Molecular Biology of the Cell (2015)
C. A. Anderson, S. Roberts*, H. Zhang*, C. M. Kelly, A. Kendall, C. Lee, J. Gerstenberger, A. B. Koenig, R. Kabeche, and A. S. Gladfelter. (*equal contribution), Ploidy variation in multinucleate cells changes under stress, Molecular Biology of the Cell (2015)
A. A. Bridges, H. Zhang, S. Mehta, P. Occhipinti, T. Tani, A. S. Gladfelter, Septin assemblies form by diffusion-driven annealing on membranes, Proceedings of the National Academy of Sciences (2014)
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