Sheen Lab Research Areas

Sheen Lab Research Summary

My laboratory has conducted research in five areas of plant biology. Research experiences in diverse signaling pathways have facilitated and enhanced new discoveries in biological principles.

1. Nutrient signaling: Glucose and nitrate are central to plant growth and development, but the molecular and cellular mechanisms of nutrient signaling have remained enigmatic for decades. We provided the first evidence for distinct HXK1 glucose sensor functions in both growth promotion and repression, which are uncoupled from glucose metabolism. We also discovered the plant glucose-TOR signaling network in reprogramming the transcriptome and activating meristems, which supply all new cells and organs in post-embryonic development. Our studies laid the foundation and continue to lead the research on distinct HXK1 glucose-sensor and glucose-TOR signaling networks. Recent discoveries reveal a surprising role of the nutrient-coupled Ca2+-signaling and Ca2+ sensor protein kinase function in integrating transcriptome and metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture. Our findings on signaling mechanisms mediated by the evolutionarily conserved HXK1 glucose sensor, TOR, and CPKs will illuminate future research on HXK, mTOR and CaMK signaling, central to plant production in agriculture and human health and diseases.

a. Moore, B., et al., Sheen, J. (2003). Role of the Arabidopsis glucose sensor HXK1 in nutrient, light and hormonal signaling. Science 300: 332-336. PMID: 12690200

b. Cho, Y.H., Yoo, S.D., Sheen, J. (2006). Regulatory functions of nuclear hexokinase1 complex in glucose signaling. Cell 127: 579-589. PMID: 17081979

c. Xiong, Y., McCormack, M., Li, L., Hall, Q., Xiang, C.B., and Sheen, J. (2013). Glucose-TOR signaling reprograms the transcriptome and activates meristems. Nature 496: 181-186. PMC4140196

d. Liu, K.H., Niu, Y., et al., Sheen, J. (2017). Discovery of nitrate-CPK-NLP signaling in central nutrient-growth networks. Nature 545: 311-316. PMID: 28489820.


Sheen, J. 2014. Master regulators in plant glucose signaling networks. J. Plant Biol 57:67-79.

Li L., Sheen, J. 2016. Dynamic and diverse sugar signaling. Curr Opin Plant Biol 33:116-125.

2. Hormone & peptide signaling: Plant chemical and peptide hormones exert central roles in plant growth and development. However, the discoveries on the molecular and cellular mechanisms of hormone sensing and signaling have been hindered by genetic redundancy and mutant embryo lethality. We pioneered integrated functional genomic screens and conditional genetic-genomic analyses that have generated seminal discoveries on the key regulatory circuitries in the auxin, cytokinin, ethylene and ABA signaling networks, and have uncovered their complex interplays and links to peptide hormone signaling. Our findings provide new concepts on signaling circuitry, hormone crosstalk, and stem cell regulation, which are key to all biological systems.

a. Hwang, I. and Sheen, J. (2001). Two-component circuitry in Arabidopsis cytokinin signal transduction. Nature 413: 383-389. PMID: 11574878

b. Müller, B. and Sheen, J. (2008). Cytokinin and auxin interplay in stem cell specification during early embryogenesis. Nature 453:1094-1097. PMCID: PMC2601652.

c. Yoo, S.D., Cho, Y.H., Tena, G., Xiong, Y., and Sheen, J. (2008). Dual control of nuclear EIN3 by bifurcate MAPK cascades in C2H4 signalling. Nature 451: 789-795. PMCID: PMC3488589

d. Lee H, Chah OK, Sheen J. (2011). Stem-cell-triggered immunity through CLV3p-FLS2 signaling. Nature 473: 376-379. PMCID: PMC3098311


Hwang, I., Sheen, J. Müller, B. 2012. Cytokinin signaling networks. Annu Rev Plant Biology 63: 353-380

Lee, H., Chah, O.K., Plotnikov, J., Sheen, J. 2012. Stem Cell Signaling in Immunity and Development. CSHL Symposium on Quantitative Biology. doi:10.1101/sqb.2012.77.014837

3. Energy-stress signaling: Plants constantly need to respond and adapt to stresses and a changing environment in order to survive and thrive in a sessile life style. For decades, prevailing models focused on stress-specific signaling pathways in plants. We discovered that evolutionarily conserved CPKs and MAPKs play pivotal roles in integrating signaling pathways stimulated by diverse stresses, and their manipulations enhance plant tolerance to multiple stresses. We also uncovered the intertwined energy-stress signaling network regulated by the Arabidopsis energy sensor kinases KIN10/11, the ortholog of yeast SNF1 and human AMPK. Our seminal findings on the unprecedented actions of KIN10/11 in transcription reprogramming and signaling networks will enhance research and applications based on the central role of plant SnRK1 and human AMPK as a key integrator of metabolism homeostasis, autophagy, immunity and aging.

a. Sheen, J. (1996). Specific Ca2+-dependent protein kinase in stress signal transduction. Science 274: 1900-1902. PMID: 8943201

b. Kovtun, Y., Chiu, W.-L. Zeng, W., and Sheen, J. (1998). Suppression of auxin signal transduction by a MAPK cascade in higher plants. Nature 395: 716-720. PMID: 9790195

c. Kovtun, Y., Chiu, W.-L. Tena, G., and Sheen, J. (2000). Functional analysis of oxidative stress-activated MAPK cascade in plants. Proc Natl Acad Sci USA 97: 2940-2945. PMCID: PMC16034

d. Baena-Gonzalez, E., Rolland, F., Thevelein, J.M. and Sheen, J. (2007). A central integrator of transcription networks in plant stress and energy signaling. Nature 448: 938-943. PMID: 17671505


Baena-González, E. and Sheen, J. 2008. Convergent energy and stress signaling. Trends in Plant Science 13: 474-481.

Boudsocq, M., Sheen, J. 2013. CDPKs in immune and stress signaling. Trends in Plant Science 18: 30-40

4. Innate immune signaling: Plants, animals and humans use analogous innate immune signaling networks to distinguish self from non-self and launch effective protection against diverse and omnipresent microbial threats. The convergent regulatory pathways mediating immune signaling from diverse sensors were hidden from conventional genetic screens due to functional redundancy and lethality. We pioneered targeted functional genomic screens to discover the central roles of specific MAPK cascades and CPKs in plant innate immune signaling networks, which respond to diverse microbial signals/proteases and plant-derived “damage” signals, secreted antimicrobial peptides, as well as diverse pathogenic effectors. We also revealed the molecular mechanisms underlying bacterial type III virulent effectors targeting plant immune co-receptors to block the action of distinct plant immune sensors. Genetic manipulations of the convergent MAPK and CPK signaling pathways enhanced resistance to broad-spectrum pathogens in plant species and crops, not previously achievable. Our discovery that the key innate immune signaling pathways mediated by PTI and ETI can be uncoupled by differential temperature environment highlights the distinct strategies that plant integrate physiological status with environmental conditions in key decision making for survival.

a. Asai, T., Tena, G., et al., and Sheen, J. (2002). MAP kinase signaling cascade in Arabidopsis innate immunity. Nature 415: 977-983. PMID: 11875555

b. He, P., Shan, L., et al. Sheen, J. (2006). Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity. Cell 125: 563-575.

c. Boudsocq, M., et al., Sheen, J. (2010). Differential innate immune signaling via Ca2+ sensor protein kinases. Nature 464: 418-422. PMCID: PMC2841715.

d. Cheng, Z., Li, J.F., et al., Sheen, J., Ausubel, F.M. (2015). Pathogen-secreted proteases activate a novel plant immune pathway. Nature 521: 213-216. PMID: 25731164; PMCID: PMC4433409.


Tena, G., Boudsocq, M. and Sheen, J. 2011. Protein kinase signaling networks in plant innate immunity Curr. Opin. Plant Biol. 14:519-529

Boudsocq, M., Sheen, J. 2013. CDPKs in immune and stress signaling. Trends in Plant Science 18: 30-40

5. Experimental method innovation: To facilitate the use of plants as powerful and fascinating systems for fundamental discoveries in biology, we enjoy and are passionate about developing new methodologies and technologies, e.g., establish powerful and versatile plant cell-based assays for targeted functional genomic screens of signaling regulators; pioneer the application of codon-optimized synthetic GFP in plants; invent protein-based artificial microRNA screens for highly effective gene silencing; and establish versatile plant codon-optimized-Cas9 and gRNA screens in diverse plant cells. We freely share detailed protocols via our website.

a. Chiu, W.-L., Niwa, Y, Zeng, W, Hirano, T., Kobayashi, H, & Sheen, J. (1996) Engineered GFP as a vital reporter in plants. Curr Biol 6: 325-330. PMID: 8805250

b. Yoo, S.D., Cho, Y.H., and Sheen, J. 2007. Arabidopsis mesophyll protoplasts: A versatile cell system for transient gene expression analysis. Nature Prot 2: 1565-1575

c. Li, J.F., Chung, H.S., Niu, Y., Bush, J., McCormack, M., & Sheen, J. (2013). Comprehensive protein-based artificial microRNA screens for effective gene silencing in plants. Plant Cell 25: 1507-1522. PMCID: PMC3694689.

d. Li, J.F., et al. & Sheen, J. (2013). Multiplex and homologous recombination-mediated plant genome editing via guide RNA/Cas9. Nature Biotech 31: 688-691. PMID: 23929339; PMC4078740.

e. Wu, H.Y., Liu, K.H., Wang, Y.-C., Wu, J.F., Chiu, W.L., Chen, C.Y., Wu, S.H., Sheen, J., Lai, E.-M. 2014. AGROBEST: an efficient Agrobacterium-mediated transient expression method for versatile gene function analysis in Arabidopsis seedlings. Plant Meth. 10: 1- 16.

f. Li, Z., Zhang, D., Xiong, X., Yan, B., Xie, W., Sheen, J., Li, J.F. 2017. A potent Cas9- derived gene activator for plant and mammalian cells. Nature Plants 3: 930-936