Lab TabsOur Research Research Interests Research in my lab focuses on elucidating the signaling mechanisms underlying growth regulation and environmental adaptation. Plants have evolved high levels of developmental plasticity, which is crucial for growth and survival in highly variable environment. Underlying such developmental plasticity are complex cellular networks that integrate perception of environmental and endogenous signals with gene expression and cell differentiation programs. One goal of our research is to gain a comprehensive understanding of the regulatory systems, and we use a wide range of research approaches, including genetics, genomics, and proteomics to achieve this goal. We are particularly effective in analyzing protein-DNA binding, protein-protein interactions, and posttranslational modifications. We study both the model organism Arabidopsis and major crops such as rice, maize and sorghum. Our long-term goal is to develop effective strategies and tools for genetic improvement of plant productivity The BR signaling network BR is a major growth-promoting hormone that regulates a wide range of developmental and physiological processes, including seed germination, cell elongation, growth, flowering, light responses, photosynthesis, and stress tolerance. Deficiency in BR synthesis or signaling causes dramatic developmental defects, including dwarfism, male sterility, delayed flowering, reduced apical dominance, and development of light-grown morphology in the dark. In contrast, application of BR or increasing BR biosynthesis can enhance plant growth and biomass production. In maize, BR also regulates sex differentiation. Research on BR can potentially lead to means of increasing crop yield and help solve the food and energy problems of the world. BR is perceived by the cell-surface receptor kinase BRI1 (Figure 1), which contains an extracellular leucine-rich repeat domain, similar to the Toll-like receptors in animals, and a cytoplasmic serine/threonine kinase domain. BR binds to the extracellular domain of BRI1 to activate its kinase and initiate a signaling cascade leading to regulation of gene expression in the nucleus. This signaling cascade includes the BR-signaling kinases (BSKs), the PP1-like phosphatase BSU1, the GSK3-like kinase BIN2, and protein phosphatase 2A (PP2A), the phosphopeptide-binding 14-3-3 proteins, and the homologous transcription factors BZR1 and BZR2 (also named BES1). When BR level is low, BIN2 phosphorylates BZR1/BZR2 and phospho-BZR1/BZR2 lose DNA binding activity and are retained in the cytoplasm by the 14-3-3 proteins. When BR level is high, BRI1 phosphorylates BSKs/CDG1 kinases which in turn phosphorylate BSU1. BSU1 dephosphorylates BIN2 to inhibit its kinase activity and to increase its ubiquitination mediated by the KIB1 E3 ubiquitin ligase. As such, BR induces rapid accumulation of dephosphorylated BZR1 and BZR2/BES1 in the nucleus due to dephosphorylation by PP2A. BZR1 and BZR2 directly regulate the expression of thousands of target genes. Our work, together with that of a handful other labs, have established the BR signaling pathway as the best-understood receptor-kinase signaling pathway in plants. Figure 1) Signal crosstalk and Integration of pathways into networks We have further gained insight into the molecular mechanism for integration of BR with other major growth-regulation signals, including gibberellin (GA), auxin, light, temperature, pathogen signals, and nutrient signals. Using modern genomic approaches of RNA-Seq and ChIP-Seq, we have identified thousands of genes directly regulated by BZR1, the light-regulated transcription factor PIF4, and the auxin response factor 6 (ARF6). These genome-wide targets not only identify diverse cellular and developmental functions controlled by these signaling pathways, but also revealed extensive overlaps among the target genes these distinct transcription factors. We further discovered that these TFs directly interact with each other and also interact with the gibberellin (GA) signaling DELLA proteins. Our research has thus revealed a central growth-regulation (CGR) network that integrates multiple hormonal and developmental pathways for growth regulation in plants (Figure 2). The CGR network also integrates additional signals such as temperature, sugar, the circadian clock. Figure 2) Genomic and Proteomic Analysis of Signaling networks To gain a comprehensive understanding of the growth regulation networks requires combinations of genetics with genomic and proteomic approaches. Modern genomic approaches, such as expression profiling and chromatin-immunoprecipitation followed by sequencing (RNA-Seq and ChIP-Seq), are powerful in identifying all target genes of a signaling pathway and revealing relationships between signaling pathways. Using these approaches, we have identified thousands of genes directly regulated by BZR1. These BZR1 target genes represent diverse cellular and developmental functions controlled by BR signaling. The BR targets include over a hundred transcription factors as well as components of other signaling pathways, such as the light, gibberellin (GA) and auxin (IAA) pathways. Similar analyses of the transcription factors controlled by light and auxin, namely PIF4 and ARF6, have revealed extensive overlaps among their target genes, which revealed a central growth-regulation network (CGN) that integrates multiple hormonal and developmental pathways for growth regulation in plants (Figure 2). Proteomics is a powerful approach for studying signal transduction. Using proteomics, we have successfully identified key components of the BR pathway such as BSKs, PP2A, TOPLESS, and many other proteins that we are still characterizing. We continue to use advanced proteomic approaches to study signal transduction mechanisms in the model plant Arabidopsis and crops such as rice, maize and rye. These studies are expanding the posttranslational modification networks that integrate BR signal with other signaling pathways. Our studies using genetic, genomic, and proteomic approaches have yielded a detailed understanding of how BR signal is transduced from the cell surface receptor kinase to nuclear transcription factors and how this BR pathway integrates and crosstalks with other signaling pathways in specific developmental contexts. Our current research focuses on the mechanisms of signal integration and the evolutionary comparison of the signaling networks in different plant species. Examples of ongoing research projects include: (1) proteomic identification and functional study of proteins that interact with known BR-signaling proteins; (2) functional study of BZR1 target genes; (3) BR regulation of stem cell dynamics in the meristems; (4) crosstalk between BR signaling pathway and other receptor kinase pathways; (5) proteomic and genomic studies of other signaling pathways in Arabidopsis and the BR pathway in maize.' Figure 3) Recent review papers Chaiwanon J, Wang W, Zhu JY, Oh E, Wang ZY. (2016) Information Integration and Communication in Plant Growth Regulation. Cell 164(6):1257-68.Wang W, Bai MY, Wang ZY. (2014). The brassinosteroid signaling network – a paradigm of signal integration. Curr. Opin. Plant Biol. 21:147–153 .Wang W and Wang ZY. (2014). At the intersection of plant growth and immunity. Cell Host Microbe 15, 400–402.Zhu JY, Sae-Seaw J, Wang ZY. (2013). Brassinosteroid signalling. Development. 140, 1615-1620.Wang ZY, Bai MY, Oh E, Zhu JY (2012). Brassinosteroid signaling network and regulation of photomorphogenesis. Annu. Rev. Genet. 46:701-724.Kim TW and Wang ZY. (2010) Brassinosteroid signal transduction from receptor kinases to transcription factors. Annu. Rev. Plant Biol.61, 681-704. Lab PI Zhiyong Wang Acting Director & Senior Staff Scientist Plant BiologyCarnegie Institution for Science firstname.lastname@example.org 650-739-4205 Office: 260 Panama StreetStanford, CA 94305, US  ProfileBioI am interested in how a plant cell transduces signals to induce desired responses and integrates diverse information into coherent and optimal decisions to optimize its chance of survival and to maximize its potential of growth. I need to do the same for my new job and I hope I can be as smart as a plant cell. AffiliationCarnegie Affiliation: DPB EmployeesDPB Affiliation: DPB FacultyOperational Division: DPB AdministrationLabs: Wang Lab Lab Members Kanako Bessho-Uehara (Postdoctoral Associate ) Yang Bi (Postdoctoral Associate) Veder Garcia (Postdoctoral Associate)Veder is interested in the molecular mechanisms that regulate plant growth. His current research project uses molecular, genetic, and proteomic approaches to understand hormone regulation of protein-trafficking in plants with the ultimate goal to increase plant biomass production. Yuchun Hsiao (Fellow)I am interested in receptor kinase function in salt signaling pathway and how the BR-auxin circuitry regulates root growth and development. Chuan-Chih Hsu (Postdoctoral Associate)I am from Taichung City, Taiwan. I obtained a BS in Agricultural Chemistry from National Taiwan University in Taipei City, Taiwan in June 2007. I then decided to study analytical chemistry so I spent two years to complete a MS in Chemistry at National Taiwan University with Dr. Yu-Ju Chen as my advisor in June 2009. I then moved to West Lafayette in Auguest 2012, and I joined Dr. Andy Tao's lab and spent time designing novel (phospho)proteomic strategies toward comprehensive phosphoproteomic analysis. I recieved my PhD degree in Biochemistry from Purdue University in September 2017, and I joined Dr. Wang's lab as a postdoc in June 2018. I am interested in the development of novel mass spectrometry(MS)-based approaches that faciliate systematically analysis of plant signal transduction and proteome perturbation in response to extracellular stimuli. I believe that MS is a cutting-edge technique to identify all the proteins involved in various biological processes and to illustrate their functional mechanisms in plant cells. My current research project focuses on the study of phosphorylation events in plants under environmental stresses. In my spare time, I enjoy jogging, watching movie, and listening to classical music. Tae-Wuk Kim (Postdoctoral Associate) Weimin Ni (Postdoctoral Associate) Chan Ho Park ( Fellow) Frej Tulin (Fellow)I am interested in how plants coordinate cell growth and division. Brassinosteroid (BR) hormones are known for their growth-promoting activity, but also help regulate cell division in certain tissues. I am exploring mechanistic links between BR signaling and cell division, using Arabidopsis and the alga Chlamydomonas as models. I received a M.S. from KTH in Stockholm, Sweden, and a Ph.D. from the Rockefeller University. I like running and ping pong. XueLian Yang (Visiting Investigator)Functional study of brassinosteroid regulated phospho-proteins. Zhenzhen Zhang (Postdoctoral Fellow)I am interested in mechanisms of plant growth regulated by sugar and brassinosteroid signaling. Jiaying Zhu (Senior Researcher )My research interest is to uncover the molecular mechanisms underlying developmental plasticity and plant growth regulation by plant hormones and environmental signals including light and temperature. Former Lab Members and Current Affiliation Postdoc/Graduate Students: Shouling Xu, Director of Proteomics at the Carnegie Institution for Science Wenfei Wang, Professor, Fujian Agriculture and Forestry University Xuelian Yang, Associate Professor, Fujian Agriculture and Forestry University Sunita Patil, Stanford University Eunkyoo Oh, Korea Por Sae-Seaw, Lecturer, Chulalongkorn U., Thailand Mingyi Bai, Professor, Shandong University, China Min Fan, Assistant Professor, Shandong University, China Tae-Wuk Kim, Assistant Professor, Hanyang U. Korea Yu Sun, Professor, Hebei Normal University, China Wenqiang Tang, Professor, Hebei Normal University, China Zhiping Deng, Group leader, Zhejiang Academy of Agricultural Sciences, China Junxian He, Assistant Professor, the Chinese University of Hong Kong Srinivas Gampala, Dow Agrosciences, USA Soo-Hwan Kim, Professor, Yonsei University, Korea Ying Sun, Professor, Hebei Normal University, China Joshua Gendron, Assistant Professor, Yale University, USA Visiting Scholars/Students/Technishia: Man Ao Ying Sun, Professor, Hebei Normal University, China Ruiju Wang, 2007-2009 Postdoc, Hebei Normal U. China Yaqi Hao, 2008-2011 Research Associate, Shannxi Normal U. China Jianxiu Shang 2009-2011 Research Associate, Hebei Normal U. China Hongjuan Yang, 2009-2010 Graduate program director, IB, CAS Rafael Augusto, 2010-2011 Univers. Federal do Rio Grande do Sul. Brazil Hak-Soo Lee 2010-2011 Student, Yonsei U. Korea Yang Bai, 2010-2012 Student, Northeast U. China Shuolei Bu, 2011-2013 Student, Hebei Normal U. China Jiangshu Liu, 2007-2009 Postdoc, U. Toronto, Canada Min Yuan, 2008-2010 Assistant Professor, Hebei Sci Tech U. China Tian Li, 2007-2009 Lecturer, Lanzhou U. China Peng Xu, 2009-2010 Postdoc, Peking U. China Hui Yang, 2008-2010 Professor, Lanzhou Institute of Biology, China Zhiguang Zhao, 2008-2009 Professor, Lanzhou University, China Tonglin Mao, 2008-2009 Associate Professor, China Agriculture U. Shengwei Zhu, 2009-2010 Group Leader, Institute of Botany, CAS, China Shuolei Bu 2010-2014 Visiting graduate student from China Chuangqi Wei, 2012-2015 Visiting graduate student from China Lauro Bücker Neto, 2012-2014 Visiting graduate student from Brazil Shengwei Zhang 2014-2015 Visiting scholar from China Undergraduate or high school students (send Zhiyong your contact if your name is missing):Catherine Qing Sun, UCSF Medical School; Joyce Xue, UC Berkeley; Jemma Taylor, University of Warwick, UK; Emily Luise Hulme, Stanford University; Andrew Ma, Cal Tech; Denial Li, UCSD. PublicationsSelected Publications (see full publication list at: https://scholar.google.com/citations?user=DSbbGNIAAAAJ&hl=en&oi=ao) Reviews: Chaiwanon J, Wang W, Zhu JY, Oh E, Wang ZY. (2016) Information Integration and Communication in Plant Growth Regulation. Cell 164(6):1257-68. Wang W, Bai MY, Wang ZY.(2014). The brassinosteroid signaling network – a paradigm of signal integration. Curr. Opin. Plant Biol. 21:147–153. Zhu JY, Sae-Seaw J, Wang ZY (2013). Brassinosteroid signalling. Development 140, 1615-1620. Wang ZY, Bai MY, Oh E, Zhu JY (2012). Brassinosteroid signaling network and regulation of photomorphogenesis. Annu. Rev. Genet. 46:701-724. Kim TW and Wang ZY. (2010) Brassinosteroid signal transduction from receptor kinases to transcription factors. Annu. Rev. Plant Biol. 61, 681-704. Research articles Tian Y, Fan M, Qin Z, Lv H, Wang M, Zhang Z, Zhou W, Zhao N, Li X, Han C, Ding Z, Wang W, Wang ZY, Bai MY. (2018). Hydrogen peroxide positively regulates brassinosteroid signaling through oxidation of the BRASSINAZOLE-RESISTANT1 transcription factor. Nat Communication14;9(1):1063. Zhu J-Y, Li Y, Cao D, Yang H, Oh E, Bi Y, Zhu S, Wang Z-Y (2017) The F-box protein KIB1 mediates brassinosteroid-induced inactivation and degradation of GSK3-like kinases in Arabidopsis. Mol Cell 66(5):648-657. Xu SL, Chalkley RJ, Maynard JC, Wang W, Ni W, Jiang X, Shin K,Cheng L, Savage D, Hühmer AFR, Burlingame AL, Wang Z-Y. (2017) Proteomic Analysis Reveals O-GlcNAc Modification on Proteins with Key Regulatory Functions in Arabidopsis. PNAS 114(8):E1536-E1543. Zhu JY, Oh E, Wang T, Wang ZY. (2016) TOC1-PIF4 interaction mediates the circadian gating of thermoresponsive growth in Arabidopsis. Nat Communication 7:13692. Zhang Z, Zhu JY, Roh J, Marchive C, Kim SK, Meyer C, Sun Y, Wang W, Wang ZY.(2016). TOR Signaling Promotes Accumulation of BZR1 to Balance Growth with Carbon Availability in Arabidopsis. Curr Biol. 26:1854-60. Chaiwanon J and Wang ZY. (2015) Spatiotemporal brassinosteroid signaling and antagonism with auxin pattern stem cell dynamics in Arabidopsis roots. Current Biology 25(8):1031-42. Ni WM, Xu SL, Tepperman JM, Stanley DJ, Maltby DA, Gross JD, Burlingame AL, Wang ZY and Quail PH(2014). A mutually assured destruction mechanism attenuates light signaling in Arabidopsis. Science 344, 1160-1164. Oh E, Zhu JY, Bai MY, and Wang ZY. (2014). A central transcription module regulates cell elongation and development by integrating major environmental and hormonal signals in Arabidopsis. eLife:e03031. Oh E, Zhu JY, Ryu H, Hwang I, Wang ZY. (2014). TOPLESS mediates brassinosteroid-induced transcriptional repression through interaction with BZR1. Nature Communications18;5:4140. Fan M, Bai MY, Kim JG, Wang T, Oh E, Chen L, Park CH, Son SH, Kim SK, Mudgett MB, Wang ZY. (2014). The bHLH transcription factor HBI1 mediates the trade-off between growth and pathogen-associated molecular pattern-triggered immunity in Arabidopsis. Plant Cell 26, 828-841. Gendron JM, Liu JS, Fan M, Bai MY, Wenkel S, Springer PS, Barton MK, Wang ZY (2012). Brassinosteroids regulate organ boundary formation in the shoot apical meristem of Arabidopsis. Proc Natl Acad Sci USA 109, 21152-21157. Bai MY, Fan M, Oh E, Wang ZY(2012) A triple-HLH/bHLH Cascade Controls Cell Elongation Downstream of Multiple Hormonal and Environmental Signaling Pathways in Arabidopsis. Plant Cell 24:4917-4929 Oh E, Zhu JY, Wang ZY. (2012). Interaction between BZR1 and PIF4 integrates brassinosteroid and environmental responses. Nature Cell Biol.14, 802-809. Bai MY, Shang JX, Oh E, Fan M, Bai Y, Zentella R, Sun TP, Wang ZY. (2012). Brassinosteroid, gibberellin, and phytochrome impinge on a common transcription module in Arabidopsis. Nature Cell Biol.14, 810-819. Kim TW, Michniewicz M, Bergmann DC, Wang ZY. (2012). Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway. Nature 482, 419-422. Hao Y, Oh E, Choi G, Liang Z, Wang ZY. (2012). Interactions between HLH and bHLH Factors Modulate Light-Regulated Plant Development. Mol. Plant 5, 688-697. Kim TW, Guan S, Burlingame AL, Wang ZY. (2011). The CDG1 Kinase Mediates Brassinosteroid Signal Transduction from BRI1 Receptor Kinase to BSU1 Phosphatase and GSK3-like Kinase BIN2. Mol. Cell 43, 561-571.PMCID: PMC3206214 Tang W, Yuan M, Wang R, Yang Y, Wang C, Oses-Prieto JA, Kim TW, Zhou HW, Deng Z, Gampala SS, Gendron JM, Jonassen EM, Lillo C, DeLong A, Burlingame AL, Sun Y, Wang ZY. (2011). PP2A activates brassinosteroid-responsive gene expression and plant growth by dephosphorylating BZR1. Nature Cell Biol.13:124-131. PMCID: PMC3077550 Sun Y, Fan XY, Cao DM, Tang W, He K, Zhu JY, He JX, Bai MY, Zhu S, Oh E, Patil S, Kim TW, Ji H, Wong WH, Rhee SY, Wang ZY. (2010). Integration of brassinosteroid signal transduction with the transcription network for plant growth regulation in Arabidopsis. Dev. Cell 19, 756-777. PMCID: PMC3018842. Luo XM, Lin WH, Zhu S, Zhu JY, Sun Y, Fan XY, Cheng M, Hao Y, Oh E, Tian M, Liu L, Zhang M, Xie Q, Chong K, Wang ZY. (2010). Integration of light- and brassinosteroid-signaling pathways by a GATA transcription factor in Arabidopsis. Dev Cell 19: 872-883. Kim TW, Guan S, Sun Y, Deng Z, Tang W, Shang JX, Sun Y, Burlingame AL, Wang ZY. (2009) Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors. Nature Cell Biol. 11, 1254-1262. Tang W, Kim TW, Oses-PrietoJA,Sun Y, Deng Z, Zhu S, Wang R, Burlingame AL, Wang ZY (2008). BSKs mediate signal transduction from the receptor kinase BRI1 in Arabidopsis. Science 321, 557-560. Gampala SS, Kim TW, He JX, Tang W, Deng Z, Bai MY, Guan S, Lalonde S, Sun Y, Gendron JM, Chen H, Shibagaki N, Ferl RJ, Ehrhardt D, Chong K, Burlingame AL, Wang ZY. (2007). An essential role for 14-3-3 proteins in brassinosteroid signal transduction in Arabidopsis.Dev. Cell 13, 177-189. Bai MY, Zhang LY, Gampala SS, Zhu SW, Song WY, Chong K, Wang ZY. (2007). Functions of OsBZR1 and 14-3-3 proteins in brassinosteroid signaling in rice. Proc.Natl. Acad. Sci. USA 104, 13939-13844. He JX, Gendron JM, Sun Y, Gampala SS, Gendron N, Sun CQ, Wang ZY (2005). BZR1 is a transcriptional repressor with dual roles in brassinosteroid homeostasis and growth responses. Science 307(5715): 1634-1638. Wang ZY, Nakano T, Gendron J, He J, Chen M, Vafeados D, Yang Y, Fujioka S, Yoshida S, Asami T, Chory J(2002). Nuclear-localized BZR1 mediates brassinosteroid-induced growth and feedback suppression of brassinosteroid biosynthesis. Dev. Cell 2(4): 505-513. Wang ZY, Seto H, Fujioka S, Yoshida S, Chory J. (2001) BRI1 is a critical component of a plasma membrane receptor for plant steroids. Nature 410(6826): 380-382. He Z, Wang ZY, Li J, Zhu Q, Lamb C, Ronald P, Chory J. (2000) Perception of brassinosteroids by the extracellular domain of the receptor kinase BRI1. Science 288(5475): 2360-2363. Weigel D, Ahn JH, Blázquez MA, Borevitz JO, Christensen SK, Fankhauser C, Ferrándiz C, Kardailsky I, Malancharuvil EJ, Neff MM, Nguyen JT, Sato S, Wang ZY, Xia Y, Dixon RA, Harrison MJ, Lamb CJ, Yanofsky MF, Chory J. (2000). Activation tagging in Arabidopsis. Plant Physiology 122(4): 1003-1013. Wang ZY, Tobin EM (1998) Constitutive expression of the CIRCADIAN CLOCK ASSOCIATED 1(CCA1) gene disrupts circadian rhythms and suppresses its own expression. Cell 93(7): 1207-1217.