Professional Education

  • Doctor of Philosophy, Yale University (2010)

Stanford Advisors

All Publications

  • Transcriptome Dynamics of the Stomatal Lineage: Birth, Amplification, and Termination of a Self-Renewing Population DEVELOPMENTAL CELL Adrian, J., Chang, J., Ballenger, C. E., Bargmann, B. O., Alassimone, J., Davies, K. A., Lau, O. S., Matos, J. L., Hachez, C., Lanctot, A., Vaten, A., Birnbaum, K. D., Bergmann, D. C. 2015; 33 (1): 107-118


    Developmental transitions can be described in terms of morphology and the roles of individual genes, but also in terms of global transcriptional and epigenetic changes. Temporal dissections of transcriptome changes, however, are rare for intact, developing tissues. We used RNA sequencing and microarray platforms to quantify gene expression from labeled cells isolated by fluorescence-activated cell sorting to generate cell-type-specific transcriptomes during development of an adult stem-cell lineage in the Arabidopsis leaf. We show that regulatory modules in this early lineage link cell types that had previously been considered to be under separate control and provide evidence for recruitment of individual members of gene families for different developmental decisions. Because stomata are physiologically important and because stomatal lineage cells exhibit exemplary division, cell fate, and cell signaling behaviors, this dataset serves as a valuable resource for further investigations of fundamental developmental processes.

    View details for DOI 10.1016/j.devcel.2015.01.025

    View details for Web of Science ID 000352454200011

  • Direct roles of SPEECHLESS in the specification of stomatal self-renewing cells SCIENCE Lau, O. S., Davies, K. A., Chang, J., Adrian, J., Rowe, M. H., Ballenger, C. E., Bergmann, D. C. 2014; 345 (6204): 1605-1609
  • Irreversible fate commitment in the Arabidopsis stomatal lineage requires a FAMA and RETINOBLASTOMA-RELATED module. eLife Matos, J. L., Lau, O. S., Hachez, C., Cruz-Ramírez, A., Scheres, B., Bergmann, D. C. 2014; 3


    The presumed totipotency of plant cells leads to questions about how specific stem cell lineages and terminal fates could be established. In the Arabidopsis stomatal lineage, a transient self-renewing phase creates precursors that differentiate into one of two epidermal cell types, guard cells or pavement cells. We found that irreversible differentiation of guard cells involves RETINOBLASTOMA-RELATED (RBR) recruitment to regulatory regions of master regulators of stomatal initiation, facilitated through interaction with a terminal stomatal lineage transcription factor, FAMA. Disrupting physical interactions between FAMA and RBR preferentially reveals the role of RBR in enforcing fate commitment over its role in cell-cycle control in this developmental context. Analysis of the phenotypes linked to the modulation of FAMA and RBR sheds new light on the way iterative divisions and terminal differentiation are coordinately regulated in a plant stem-cell lineage.

    View details for DOI 10.7554/eLife.03271

    View details for PubMedID 25303364

  • Arabidopsis FHY3 and HY5 Positively Mediate Induction of COP1 Transcription in Response to Photomorphogenic UV-B Light PLANT CELL Huang, X., Ouyang, X., Yang, P., Lau, O. S., Li, G., Li, J., Chen, H., Deng, X. W. 2012; 24 (11): 4590-4606


    As sessile organisms, higher plants have evolved the capacity to sense and interpret diverse light signals to modulate their development. In Arabidopsis thaliana, low-intensity and long-wavelength UV-B light is perceived as an informational signal to mediate UV-B-induced photomorphogenesis. Here, we report that the multifunctional E3 ubiquitin ligase, CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1), a known key player in UV-B photomorphogenic responses, is also a UV-B-inducible gene. Two transcription factors, FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and ELONGATED HYPOCOTYL5 (HY5), directly bind to distinct regulatory elements within the COP1 promoter, which are essential for the induction of the COP1 gene mediated by photomorphogenic UV-B signaling. Absence of FHY3 results in impaired UV-B-induced hypocotyl growth and reduced tolerance against damaging UV-B. Thus, FHY3 positively regulates UV-B-induced photomorphogenesis by directly activating COP1 transcription, while HY5 promotes COP1 expression via a positive feedback loop. Furthermore, FHY3 and HY5 physically interact with each other, and this interaction is diminished by UV-B. Together, our findings reveal that COP1 gene expression in response to photomorphogenic UV-B is controlled by a combinatorial regulation of FHY3 and HY5, and this UV-B-specific working mode of FHY3 and HY5 is distinct from that in far-red light and circadian conditions.

    View details for DOI 10.1105/tpc.112.103994

    View details for Web of Science ID 000313272700023

    View details for PubMedID 23150635

  • Stomatal development: a plant's perspective on cell polarity, cell fate transitions and intercellular communication DEVELOPMENT Lau, O. S., Bergmann, D. C. 2012; 139 (20): 3683-3692


    The plant stomatal lineage manifests features common to many developmental contexts: precursor cells are chosen from an initially equivalent field of cells, undergo asymmetric and self-renewing divisions, communicate among themselves and respond to information from a distance. As we review here, the experimental accessibility of these epidermal lineages, particularly in Arabidopsis, has made stomata a conceptual and technical framework for the study of cell fate, stem cells, and cell polarity in plants.

    View details for DOI 10.1242/dev.080523

    View details for Web of Science ID 000308976300003

    View details for PubMedID 22991435

  • The photomorphogenic repressors COP1 and DET1: 20 years later TRENDS IN PLANT SCIENCE Lau, O. S., Deng, X. W. 2012; 17 (10): 584-593


    COP1 and DET1 are among the first repressors of photomorphogenesis to be identified, more than 20 years ago. Discovery of these repressors as conserved regulators of the ubiquitin-proteasome system has established protein degradation as a central theme in light signal transduction. COP1 is a RING E3 ubiquitin ligase that targets key regulators for degradation, and DET1 complexes with COP10 and DDB1, which is proposed to aid in COP1-mediated degradation. Recent studies have strengthened the role of COP1 as a major signaling center. DET1 is also emerging as a chromatin regulator in repressing gene expression. Here, we review current understanding on COP1 and DET1, with a focus on their role as part of two distinct, multimeric CUL4-based E3 ligases.

    View details for DOI 10.1016/j.tplants.2012.05.004

    View details for Web of Science ID 000310420300004

    View details for PubMedID 22705257

  • Interaction of Arabidopsis DET1 with CCA1 and LHY in Mediating Transcriptional Repression in the Plant Circadian Clock MOLECULAR CELL Lau, O. S., Huang, X., Charron, J., Lee, J., Li, G., Deng, X. W. 2011; 43 (5): 703-712


    The COP10-DET1-DDB1 (CDD) complex is an evolutionarily conserved protein complex discovered for its role in the repression of photomorphogenesis in Arabidopsis. It is important in many cellular and developmental processes in both plants and animals, but its molecular mode of action remains poorly understood. Here, we show that the CDD component DET1 possesses transcriptional repression activity and physically interacts with two closely related MYB transcription factors, CCA1 and LHY, which are core components of the plant circadian clock. DET1 associates with the promoter of CCA1/LHY target genes, such as TOC1, in a CCA1/LHY-dependent manner and is required for their repression, suggesting a recruitment of DET1 by the central oscillator components to regulate the clock. Our results reveal DET1 as a core transcriptional repression factor important for clock progression. Overall, the CDD complex may function as a transcriptional corepressor in diverse processes through direct interaction with distinct transcription factors.

    View details for DOI 10.1016/j.molcel.2011.07.013

    View details for Web of Science ID 000294593300006

    View details for PubMedID 21884973

  • Coordinated transcriptional regulation underlying the circadian clock in Arabidopsis NATURE CELL BIOLOGY Li, G., Siddiqui, H., Teng, Y., Lin, R., Wan, X., Li, J., Lau, O., Ouyang, X., Dai, M., Wan, J., Devlin, P. F., Deng, X. W., Wang, H. 2011; 13 (5): 616-U275


    The circadian clock controls many metabolic, developmental and physiological processes in a time-of-day-specific manner in both plants and animals. The photoreceptors involved in the perception of light and entrainment of the circadian clock have been well characterized in plants. However, how light signals are transduced from the photoreceptors to the central circadian oscillator, and how the rhythmic expression pattern of a clock gene is generated and maintained by diurnal light signals remain unclear. Here, we show that in Arabidopsis thaliana, FHY3, FAR1 and HY5, three positive regulators of the phytochrome A signalling pathway, directly bind to the promoter of ELF4, a proposed component of the central oscillator, and activate its expression during the day, whereas the circadian-controlled CCA1 and LHY proteins directly suppress ELF4 expression periodically at dawn through physical interactions with these transcription-promoting factors. Our findings provide evidence that a set of light- and circadian-regulated transcription factors act directly and coordinately at the ELF4 promoter to regulate its cyclic expression, and establish a potential molecular link connecting the environmental light-dark cycle to the central oscillator.

    View details for DOI 10.1038/ncb2219

    View details for Web of Science ID 000290148700021

    View details for PubMedID 21499259

  • Production of the 42-kDa fragment of Plasmodium falciparum merozoite surface protein 1, a leading malaria vaccine antigen, in Arabidopsis thaliana seeds PLANT BIOTECHNOLOGY JOURNAL Lau, O. S., Ng, D. W., Chan, W. W., Chang, S. P., Sun, S. S. 2010; 8 (9): 994-1004


    Malaria is widely associated with poverty, and a low-cost vaccine against malaria is highly desirable for implementing comprehensive vaccination programmes in developing countries. Production of malaria antigens in plants is a promising approach, but its development has been hindered by poor expression of the antigens in plant cells. In the present study, we targeted plant seeds as a low-cost vaccine production platform and successfully expressed the Plasmodium falciparum 42-kDa fragment of merozoite surface protein 1 (MSP1??), a leading malaria vaccine candidate, at a high level in transgenic Arabidopsis seeds. We overcame hurdles of transcript and protein instabilities of MSP1?? in plants by synthesizing a plant-optimized MSP1?? cDNA and either targeting the recombinant protein to protein storage vacuoles or fusing it with a stable plant storage protein. An exceptional improvement in MSP1?? expression, from an undetectable level to 5% of total extractable protein, was achieved with these combined strategies. Importantly, the plant-derived MSP1?? maintains its natural antigenicity and can be recognized by immune sera from malaria-infected patients. Our results provide a strong basis for the development of a plant-based, low-cost malaria vaccine.

    View details for DOI 10.1111/j.1467-7652.2010.00526.x

    View details for Web of Science ID 000283983100005

    View details for PubMedID 20444208

  • Plant hormone signaling lightens up: integrators of light and hormones CURRENT OPINION IN PLANT BIOLOGY Lau, O. S., Deng, X. W. 2010; 13 (5): 571-577


    Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3-LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact.

    View details for DOI 10.1016/j.pbi.2010.07.001

    View details for Web of Science ID 000284658400014

    View details for PubMedID 20739215

  • Arabidopsis CULLIN4-Damaged DNA Binding Protein 1 Interacts with CONSTITUTIVELY PHOTOMORPHOGENIC1-SUPPRESSOR OF PHYA Complexes to Regulate Photomorphogenesis and Flowering Time PLANT CELL Chen, H., Huang, X., Gusmaroli, G., Terzaghi, W., Lau, O. S., Yanagawa, Y., Zhang, Y., Li, J., Lee, J., Zhu, D., Deng, X. W. 2010; 22 (1): 108-123


    CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) possesses E3 ligase activity and promotes degradation of key factors involved in the light regulation of plant development. The finding that CULLIN4 (CUL4)-Damaged DNA Binding Protein1 (DDB1) interacts with DDB1 binding WD40 (DWD) proteins to act as E3 ligases implied that CUL4-DDB1 may associate with COP1-SUPPRESSOR OF PHYA (SPA) protein complexes, since COP1 and SPAs are DWD proteins. Here, we demonstrate that CUL4-DDB1 physically associates with COP1-SPA complexes in vitro and in vivo, likely via direct interaction of DDB1 with COP1 and SPAs. The interactions between DDB1 and COP1, SPA1, and SPA3 were disrupted by mutations in the WDXR motifs of MBP-COP1, His-SPA1, and His-SPA3. CUL4 cosuppression mutants enhanced weak cop1 photomorphogenesis and flowered early under short days. Early flowering of short day-grown cul4 mutants correlated with increased FLOWERING LOCUS T transcript levels, whereas CONSTANS transcript levels were not altered. De-etiolated1 and COP1 can bind DDB1 and may work with CUL4-DDB1 in distinct complexes, but they mediate photomorphogenesis in concert. Thus, a series of CUL4-DDB1-COP1-SPA E3 ligase complexes may mediate the repression of photomorphogenesis and, possibly, of flowering time.

    View details for DOI 10.1105/tpc.109.065490

    View details for Web of Science ID 000275926100011

    View details for PubMedID 20061554

  • Plant seeds as bioreactors for recombinant protein production BIOTECHNOLOGY ADVANCES Lau, O. S., Sun, S. S. 2009; 27 (6): 1015-1022


    Plants are attractive expression systems for the economic production of recombinant proteins. Among the different plant-based systems, plant seed is the leading platform and holds several advantages such as high protein yields and stable storage of target proteins. Significant advances in using seeds as bioreactors have occurred in the past decade, which include the first commercialized plant-derived recombinant protein. Here we review the current progress on seeds as bioreactors, with focus on the different food crops as production platforms and comprehensive strategies in optimizing recombinant protein production in seeds.

    View details for DOI 10.1016/j.biotechadv.2009.05.005

    View details for Web of Science ID 000271554200030

    View details for PubMedID 19460423

  • Effect of Arabidopsis COP10 ubiquitin E2 enhancement activity across E2 families and functional conservation among its canonical homologues BIOCHEMICAL JOURNAL Lau, O. S., Deng, X. W. 2009; 418: 683-690


    Arabidopsis thaliana COP10 (constitutive photomorphogenic 10) is a UEV [Ub (ubiquitin)-conjugating enzyme (E2) variant protein] that is required for repression of seedling photomorphogenesis in darkness. COP10 forms a complex {the CDD complex [COP10-DET1 (de-etiolated 1)-DDB1 (DNA damage binding protein 1) complex]} with DET1 and DDB1a in vivo and can enhance the activity of Ub-conjugating enzyme (E2) in vitro. To investigate whether COP10 might act as a general regulator of E2s, we tested the specificity of COP10 E2 enhancement activity across E2 families of Arabidopsis. We found that COP10 is capable of enhancing members of four E2 subgroups significantly, while having a milder effect on another. Surprisingly, we found that close canonical E2 homologues of COP10, such as UbcH5a (human ubiquitin-conjugating enzyme 5), are also capable of enhancing E2s. Furthermore, we detected direct interactions between COP10 and three of the enhanced E2s, hinting at a possible mechanism for the enhancements. The present study suggests that some E2s, including the generic Ubc4/5p families involved in many processes, might possess dual activities: the formation of the classic E2-Ub thiol ester and the previously unknown E2 enhancement activity. Therefore COP10, despite being a catalytically inactive E2, might still enhance a variety of E2s and regulate numerous aspects of plant development.

    View details for DOI 10.1042/BJ20081943

    View details for Web of Science ID 000264145300020

    View details for PubMedID 19061479

  • Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2 ubiquitin-conjugating enzymes MOLECULAR AND CELLULAR BIOLOGY Pick, E., Lau, O., Tsuge, T., Menon, S., Tong, Y., Dohmae, N., Plafker, S. M., Deng, X. W., Wei, N. 2007; 27 (13): 4708-4719


    DET1 (de-etiolated 1) is an essential negative regulator of plant light responses, and it is a component of the Arabidopsis thaliana CDD complex containing DDB1 and COP10 ubiquitin E2 variant. Human DET1 has recently been isolated as one of the DDB1- and Cul4A-associated factors, along with an array of WD40-containing substrate receptors of the Cul4A-DDB1 ubiquitin ligase. However, DET1 differs from conventional substrate receptors of cullin E3 ligases in both biochemical behavior and activity. Here we report that mammalian DET1 forms stable DDD-E2 complexes, consisting of DDB1, DDA1 (DET1, DDB1 associated 1), and a member of the UBE2E group of canonical ubiquitin-conjugating enzymes. DDD-E2 complexes interact with multiple ubiquitin E3 ligases. We show that the E2 component cannot maintain the ubiquitin thioester linkage once bound to the DDD core, rendering mammalian DDD-E2 equivalent to the Arabidopsis CDD complex. While free UBE2E-3 is active and able to enhance UbcH5/Cul4A activity, the DDD core specifically inhibits Cul4A-dependent polyubiquitin chain assembly in vitro. Overexpression of DET1 inhibits UV-induced CDT1 degradation in cultured cells. These findings demonstrate that the conserved DET1 complex modulates Cul4A functions by a novel mechanism.

    View details for DOI 10.1128/MCB.02432-06

    View details for Web of Science ID 000247569200010

    View details for PubMedID 17452440

  • Light-regulated transcriptional networks in higher plants NATURE REVIEWS GENETICS Jiao, Y., Lau, O. S., Deng, X. W. 2007; 8 (3): 217-230


    Plants have evolved complex and sophisticated transcriptional networks that mediate developmental changes in response to light. These light-regulated processes include seedling photomorphogenesis, seed germination and the shade-avoidance and photoperiod responses. Understanding the components and hierarchical structure of the transcriptional networks that are activated during these processes has long been of great interest to plant scientists. Traditional genetic and molecular approaches have proved powerful in identifying key regulatory factors and their positions within these networks. Recent genomic studies have further revealed that light induces massive reprogramming of the plant transcriptome, and that the early light-responsive genes are enriched in transcription factors. These combined approaches provide new insights into light-regulated transcriptional networks.

    View details for DOI 10.1038/nrg2049

    View details for Web of Science ID 000244274400015

    View details for PubMedID 17304247

  • Characterization of the ubiquitin E2 enzyme variant gene family in Arabidopsis JOURNAL OF INTEGRATIVE PLANT BIOLOGY Zhang, Y., Wen, P., Lau, O., Deng, X. 2007; 49 (1): 120-126
  • Genome analysis and functional characterization of the E2 and RING-type E3 ligase ubiquitination enzymes of Arabidopsis PLANT PHYSIOLOGY Kraft, E., Stone, S. L., Ma, L. G., Su, N., Gao, Y., Lau, O. S., Deng, X. W., Callis, J. 2005; 139 (4): 1597-1611


    Attachment of ubiquitin to substrate proteins is catalyzed by the three enzymes E1, E2 (ubiquitin conjugating [UBC]), and E3 (ubiquitin ligase). Forty-one functional proteins with a UBC domain and active-site cysteine are predicted in the Arabidopsis (Arabidopsis thaliana) genome, which includes four that are predicted or shown to function with ubiquitin-like proteins. Only nine were previously characterized biochemically as ubiquitin E2s. We obtained soluble protein for 22 of the 28 uncharacterized UBCs after expression in Escherichia coli and demonstrated that 16 function as ubiquitin E2s. Twelve, plus three previously characterized ubiquitin E2s, were also tested for the ability to catalyze ubiquitination in vitro in the presence of one of 65 really interesting new gene (RING) E3 ligases. UBC22, UBC19-20, and UBC1-6 had variable levels of E3-independent activity. Six UBCs were inactive with all RINGs tested. Closely related UBC8, 10, 11, and 28 were active with the largest number of RING E3s and with all RING types. Expression analysis was performed to determine whether E2s or E3s were expressed in specific organs or under specific environmental conditions. Closely related E2s show unique patterns of expression and most express ubiquitously. Some RING E3s are also ubiquitously expressed; however, others show organ-specific expression. Of all the organs tested, RING mRNAs are most abundant in floral organs. This study demonstrates that E2 diversity includes examples with broad and narrow specificity toward RINGs, and that most ubiquitin E2s are broadly expressed with each having a unique spatial and developmental pattern of expression.

    View details for DOI 10.1104/pp.105.067983

    View details for Web of Science ID 000233903600005

    View details for PubMedID 16339806