Yixian
Zheng
Yixian Zheng is Director of the Department of Embryology. The Zheng Lab has a long-standing interest in cell division and cytoskeleton. In recent years, their findings have broadened their research using animal models to include the study of stem cells, genome organization, and lineage specification—how stem cells differentiate into their final cell forms.
Research
The Zheng Lab uses a wide range of tools and systems in their work, including genetics in model organisms, model organism development, cell culture, biochemistry, proteomics, and genomics. In recent years, their findings have broadened their research scope to include three research areas: 1) The mechanism of cell division. 2) The mechanism of genome organization in development, homeostasis, and aging. 3) The mechanism of endosymbiosis in cnidaria.
Current Topics
The way a progenitor cell partitions itself during cell division has a profound influence on the behavior and fate of its daughter cells. Understanding this partitioning requires us to study both the mechanism of equal chromosome segregation and the means a dividing cell segregates critical cell fate determinants into daughter cells. The mitotic spindle apparatus is one of the most complex cellular machines consisting of microtubules, microtubule-associated proteins (MAPs), and motors. The spindle also associates with many poorly defined proteins and membranes. Historically these spindle-associated materials are called the spindle matrix. The importance of the spindle matrix and the value of studying it have remained a subject of debate.
We have uncovered protein complexes called γ-tubulin ring complex (γTuRC) and γ-tubulin small complex (γTuSC) that mediate microtubule nucleation and organization in mitotic and interphase cells. Through the study of microtubule nucleation, we became fascinated by the more complex and dynamic behaviors of microtubules during mitotic spindle assembly. By using the powerful Xenopus egg extract, we and others have uncovered an important signaling pathway mediated by the nuclear small GTPase Ran that regulates multiple aspects of cell division. We show that RanGTPase also regulates the assembly of the spindle matrix containing lamin-B. Based on our studies, we propose that RanGTP and the spindle matrix promote both spindle assembly and orientation. Consistent with this, we show that the spindle matrix component lamin-B regulates spindle orientation in neural stem cells in the developing mouse brain. Lamin-B may do so in part by regulating centrosome positioning.
The complexity of the spindle matrix has made the study of its structure and function relationship very difficult, which contributes to the debate of its function and even existence. By studying another spindle matrix component BuGZ, which we discovered through proteomic analyses of the Xenopus spindle matrix, we show that protein phase separation/transition represents a biophysical property of the spindle matrix. The phase separation of BuGZ along spindle microtubules promotes spindle matrix assembly, which in turn facilitates spindle microtubule assembly by concentrating tubulin. This finding opens the door to further characterize the structure and function of the spindle matrix in cell division.
The nuclear lamina and chromatin-bound proteins are known to regulate genome organization in interphase cells, yet how cells in different lineages acquire and maintain their unique genome architecture has remained poorly understood. We use various tools in genetics, genomics (such as ChIP-seq, RNA-seq, single cell RNA-seq, and Hi-C), cell biology, and biochemistry to study how genomes obtain their organization in stem cells (including ES cells) and differentiated cells isolated from tissues. We also analyze whether such organization plays a role in lineage specification or terminal differentiation, how such organization is maintained in adulthood, and whether genome dis-organization leads to age-associated diseases. For example, our recent studies demonstrate that lamin-B (the major structural component of the nuclear lamina) is not required for early lineage specification during development, but it is essential for proper organogenesis. Aging-associated lamin-B reduction in Drosophila fat bodies (equivalent to human fat and liver) leads to system inflammation and gut hyperplasia. These and other published and ongoing studies in the lab are allowing us to dissect the role of genome organization in the context of development, tissue function, and aging.
Many cnidaria species, including Hydra, upside-down jellyfish, and hard and soft corals harbor algae for photosynthesis. The algae live inside coral cells in a specialized membrane compartment called symbiosome, which shares the photosynthetically fixed carbon with coral host cells, while host cells provide inorganic carbon for photosynthesis. The molecular pathways in cnidaria cells that orchestrate algal recognition, uptake, nutrient sharing, and maintenance remain poorly understood. We have built facilities to grow various cnidaria species and have begun to create model organisms to understand cnidaria endosymbiosis.
Lab Members
Graduate Students
Timeline
CV
- 1980 – 1984 | B.S. in Genetics, Sichuan University, Sichuan, China.
- 1987 – 1992 | Ph.D. in Molecular Genetics, The Ohio State University, Columbus, OH (Advisor: Berl Oakley).
- 1992 – 1996 | Postdoctoral Fellow, University of California, San Francisco, CA (Advisors: Bruce Alberts and Tim Mitchison).
- 1984 – 1986 | Lecturer, Southwestern Agricultural University, Sichuan, China.
- 1996 – Present | Staff Member/Investigator, Department of Embryology, Carnegie Institution for Science, Baltimore, MD.
- 1996 – Present | Adjunct Assistant Professor, Associate Professor (2002), Professor (2007), Department of Biology, Johns Hopkins University.
- 2000 – 2012 | Adjunct Assistant Professor, Associate Professor (2002), Professor (2007), Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine.
- 2000 – 2012 | HHMI Investigator, Howard Hughes Medical Institute.
- 2016 – 2017 | Acting Director, Dept. of Embryology, Carnegie Institution for Science.
- 2017 – Present | Director, Dept. of Embryology, Carnegie Institution for Science.
- 2018 – 2018 | Interim Co-President, Carnegie Institution for Science.
- 1997 – 2001 | PEW Scholar Award (Awarded by PEW Charitable Trusts).
- 1997 – Present | NIH R01 and R21 Research Grants.
- 1999 | Women in Cell Biology Award (Junior) (Awarded by the American Society for Cell Biology).
- 2000 – 2012 | HHMI Investigator, Howard Hughes Medical Institute.
- 10/2006 | Douglas D. McGregor Research Keynote Speaker, Cornell University
- 07/2007 | Keynote Speaker, Gordon Conference - Motile & Contractile Systems.
- 2008 | National Associate of the National Research Council, the National Academies of Sciences (An honorary lifetime appointment for extraordinary service to the National Research Council of the National Academies of Sciences).
- 2012 – 2016 | Senior Scholar in Aging, Ellison Medical Foundation.
- 2017 | Fellow, American Society for Cell Biology (ASCB).
- 2020 – 2025 | Investigator, Gordon and Betty Moore Foundation (Symbiosis in Aquatic Systems).
- 2022 – Present | Member, R35 awards to early career investigators, Center for Scientific Review, NIH.
- 2013 – 2020 | Member, NCSD Study Section (Nuclear and Cytoplasmic Structure/Function and Dynamics), Center for Scientific Review, NIH.
- 2016 – 2019 | Chair, International Affairs Committee, American Society of Cell Biology.
- 2018 – 2021 | Member, Wellcome Trust Interview Panel (for Grant Funding).
- 2013 – Present | National Scientific Advisory Council (NSAC); American Federation for Aging Research (AFAR).
- 2011 – 2013 | Council Member, the Council of American Society for Cell Biology (ASCB).
- 2011 – 2013 | Member, International Affairs Committee, American Society for Cell Biology.
- 2007 – 2008 | Member, Program Committee, American Society for Cell Biology.
- 2005 – 2007 | Study Section NDT (Nuclear Dynamics and Transport), Center for Scientific Review (CSR), NIH.
- 2003 – 2004 | Study Section CDF4 (Cell Development and Function 4), Center for Scientific Review (CSR), NIH.
- 1999 – 2006 | Member, Woman in Cell Biology Committee, American Society for Cell Biology.
- 2001 – 2004 | Member of Organizing Committee, The Chinese-American Frontiers of Science, a special program of the US National Academy of Sciences.
- 2000 – 2002 | Prostate Cancer CBY2 Review Group, Department of Defense, United States.
- 2002 | Review Committee for Northwestern University School of Medicine
- Department of Cell Biology.
- 2001 | Review committee for International Scholar’s Program, Howard Hughes Medical Institute.
- 2001 | Chair, Local Arrangements Committee, 41st Annual Meeting, The American Society for Cell Biology, December 8-12, 2001, DC.