John Clark Lagarias

J. Clark Lagarias

Position Title
Distinguished Professor

Department of Molecular and Cellular Biology, College of Biological Sciences

31A Briggs Hall

Profile Introduction

Modern agriculture relies on crops that have been carefully tailored for environments by selective breeding. Phytochromes are attractive targets for crop improvement efforts aimed to enhance seed germination, seedling establishment, plant architecture and flowering time. The overall goal of this research is to understand the structural basis of both photosensory and regulatory functions of phytochromes from cyanobacteria to plants. Such basic knowledge will be leveraged for development of new strategies to alter the light responsiveness of agriculturally significant plant species. For example, our discovery of dominant photochemically uncoupled phytochrome alleles holds significant promise for crop improvement. Such plant-derived reagents may overcome environmental concerns while addressing the pressing need for increased food production on a finite amount of arable land needed to nourish the growing world population.

Research Interests

Molecular and Synthetic Photobiology

Research in my laboratory focuses on the phytochrome superfamily, light sensing biliproteins that are widespread in eukaryotes (plants, algae, fungi, oomycetes and diatoms) and prokaryotes (both photosynthetic and non-photosynthetic species). Phytochromes and cyanobacteriochromes are light-switches whose function depends on the light color. Plants, algae and cyanobacteria use these pigmented protein sensors to regulate photosynthesis-associated gene expression for optimum photosynthesis under the ambient light conditions and for regulation of growth, movement or reproduction to avoid suboptimal light conditions. Our studies utilize representative species from all lineages of oxygenic photosynthetic organisms, including cyanobacteria, green alga and plants. Mainly biochemical in nature, our research focuses on structure-function and molecular evolution of these optogenetic light sensors. Ongoing research seeks to leverage this knowledge for synthetic biological applications that seek to optimize yield and agronomic performance of photosynthetic species for food, fiber and energy production.

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Chemistry
  • Plant Biology

Specialties / Focus

  • Biochemistry
  • Cell and Developmental Biology
  • Environmental and Integrative Biology
  • Gene Regulation
  • Molecular Biology, Biochemistry and Genomics
  • Molecular Genetics
  • Molecular Microbiology
  • Organelle and Membrane Biology
  • Plant Molecular Biology
  • Signal Transduction
  • Structural Biology
  • Vision


  • MCB 120L Biochemistry Laboratory


  • 31 Briggs Hall
    • Marcus V. Moreno, BMCDB Graduate Student; Nathan Rockwell, Project Scientist; Wei Hu, Project Scientist; Manuel Mora and Farva Batool, Undergrads; Shelley Martin, SRA

Honors and Awards

  • 1999 Paul K. and Ruth R. Stumpf Professor of Plant Biochemistry
  • 2001 Elected to the National Academy of Sciences
  • 2010 Pollard Memorial Lecturer (Pennsylvania State University)
  • 2013 Halocarbon Corporation Lecturer (Cornell University)
  • 2016 Shang Fa-Yang Lecturer (Academia Sinica, Taipei Taiwan)
  • 2017 Elected Fellow of American Society of Plant Biologists

    Professional Societies

    • American Society of Plant Biologists
    • American Chemical Society


    • 1975 BA Botany and Chemistry University of California, Berkeley
    • 1979 PhD Chemistry University of California, Berkeley


    Kirpich J. S., Mix, L.T., Martin, S. S., Rockwell, N. C., Lagarias, J. C. and Larsen, D. S. (2018) Protonation heterogeneity modulates the ultrafast photocycle initiation dynamics of phytochrome Cph1. Journal of Physical Chemical Letters 9(12):3454-3462 PMID: 29874080

    Kirpich J. S., Chang, C. W., Madsen, D., Gottlieb, S. M., Martin, S. S., Rockwell, N. C., Lagarias, J. C. and Larsen, D. S. (2018) Noncanonical photodynamics of the orange/green cyanobacteriochrome power sensor NpF2164g7 from the PtxD phototaxis regulator of Nostoc punctiforme. Biochemistry 57(18):2636-2648. PMID: 29633829

    Blain-Hartung M., Rockwell, N. C., Moreno, M. V., Martin, S. S., Gan, F., Bryant, D. A. and Lagarias, J. C. (2018) Cyanobacteriochrome-based photoswitchable adenylyl cyclases (cPACs) for broad spectrum light regulation of cAMP levels in cells. Journal of Biological Chemistry 293(22):8473-8483 PMID: 29632072

    Lim S., Yu, Q., Gottlieb, S. M., Chang, C.-W., Rockwell, N. C., Martin, S. S., Madsen, D., Lagarias, J. C., Larsen, D. S. and Ames, J. B. (2018) Correlating structural and photochemical heterogeneity in cyanobacteriochrome NpR6012g4. Proceedings of the National Academy of Sciences (USA) 115(17), 4387-4392 PMID: 29632180

    Wittkopp, T.M., Schmollinger, S., Saroussi, S., Hu, W., Zhang, W., Fan, Q., Gallaher, S.D., Leonard, M.T., Soubeyrand, E., Basset, G.J., Merchant, S.S., Grossman, A.R., Duanmu, D. and Lagarias, J.C. (2017) Bilin-dependent photoacclimation in Chlamydomonas reinhardtii. Plant Cell 29(11), 2711-2726. PMID:29084873

    Blain-Hartung, M., Rockwell, N.C. and Lagarias, J.C. (2017) Light-regulated synthesis of cyclic-di-GMP by a bidomain construct of the cyanobacteriochrome Tlr0924 (SesA) without stable dimerization. Biochemistry 56(46), 6145-6154. PMID: 29072834

    Rockwell, N.C. and Lagarias, J.C. (2017) Ferredoxin-dependent bilin reductases in eukaryotic algae: ubiquity and diversity. Journal of Plant Physiology 217, 57-67. PMID: 28641882

    Baloban, M., Shcherbakova, D.M., Pletnev, S., Pletnev, V.Z., Lagarias, J.C., and Verkhusha, V.V. (2017) Designing brighter near-infrared fluorescent proteins: insights from structural and biochemical studies. Chemical Science 8, 4546-4557. PMID: 28936332

    Rockwell, N.C. and Lagarias, J.C. (2017) Phytochrome diversification in cyanobacteria and eukaryotic algae. Current Opinion in Plant Biology 37, 87-89. PMID: 28445833

    Duanmu, D., Rockwell, N.C., & Lagarias, J.C. (2017) Algal light sensing and photoacclimation in aquatic environments. Plant Cell and Environment 40(11):2558–2570. PMID: 28245058

    Rockwell, N.C., Martin, S.S., and Lagarias, J.C. (2017) There and back again: Loss and reacquisition of two-Cys photocycles in cyanobacteriochromes, Photochemistry and Photobiology 93, 741-754. PMID: 28055111

    Rockwell, N.C., Martin, S.S., Li, F.-W., Mathews, S., and Lagarias, J.C. (2017) The phycocyanobilin chromophore of streptophyte algal phytochromes is synthesized by HY2. New Phytologist 214, 1145-1157. PMID:28106912

    Hu, W. and Lagarias, J.C. (2017) A tightly regulated genetic selection system with signaling-active alleles of phytochrome B. Plant Physiology 173, 366-375. PMID: 27881727

    Fushimi, K., Rockwell, N.C., Enomoto, G., Win, N.-N., Martin, S.S., Gan, F., Bryant, D.A., Ikeuchi, M., Lagarias, J.C., and Narikawa, R. (2016) Cyanobacteriochrome photoreceptors lacking the canonical Cys residue. Biochemistry 55(50), 6981-6995. PMID: 27935696

    Rockwell, N.C., Martin, S.S., and Lagarias, J.C. (2016) Identification of cyanobacteriochromes detecting far-red light. Biochemistry 55(28), 3907-3919

    Chang, C.W., Gottlieb, S.M., Rockwell, N.C., Martin, S.S., Lagarias, J.C., and Larsen, D.S. (2016) Tracking the secondary photodynamics of the green/red cyanobacteriochrome RcaE from Fremyella diplosiphon. Chemical Physics Letters 644, 225-230

    Lim, S., Yu, Q., Rockwell, N.C., Martin, S.S., Lagarias, J.C., and Ames, J.B. (2016) 1H, 13C, and 15N chemical shift assignments of cyanobacteriochrome NpR6012g4 in the green-absorbing photoproduct state. Biomolecular NMR Assignments 10(1), 157-161

    Yu, Q., Lim, S., Rockwell, N.C., Martin, S.S., Lagarias, J.C., and Ames, J.B. (2016) 1H, 13C, and 15N chemical shift assignments of cyanobacteriochrome NpR6012g4 in the red-absorbing dark state. Biomolecular NMR Assignments 10(1), 139-142

    Jones MA, Hu W, Litthauer S, Lagarias JC and Harmer SL (2015) A constitutively active allele of phytochrome B maintains circadian robustness in in the absence of light and photosynthetic inputs. Plant Physiology 169(1), 814-825

    Berlin S, Carroll EC, Newman ZL, Okada HO, Quinn CM, Kallman B, Rockwell NC, Martin SS, Lagarias JC and Isacoff EY (2015) Photoactivatable Genetically-Encoded Calcium Indicators for Targeted Neuronal Imaging. Nature Methods 12(9), 852-858

    Rockwell NC, Martin SS, Lim S, Lagarias JC and Ames JB (2015) Characterization of red/green cyanobacteriochrome NpR6012g4 by solution NMR spectroscopy: A hydrophobic pocket for the C15-E,anti chromophore in the photoproduct. Biochemistry, 54(24), 3772-3783

    Rockwell NC, Martin SS, Lim S, Lagarias JC and Ames JB (2015) Characterization of red/green cyanobacteriochrome NpR6012g4 by solution NMR spectroscopy: A protonated bilin chromophore in both photostates. Biochemistry 54(16), 2581-2600

    Rockwell NC, Martin SS, and Lagarias JC (2015) Identification of DXCF cyanobacteriochrome lineages with predictable photocycles. Photochemical and Photobiological Sciences 14(5), 929-941.

    Gottlieb SM, Kim PW, Chang C-W, Hanke S, Hayer R, Rockwell NC, Martin SS, Lagarias JC and Larsen DS  (2015) Conservation and diversity in the primary forward photodynamics of red/green cyanobacteriochromes. Biochemistry 54(4), 1028-1042 

    Rockwell NC, Martin SS, Gan F, Bryant DA, and Lagarias JC (2015) NpR3784 is the prototype for a distinctive group of red/green cyanobacteriochromes using alternative Phe residues for photoproduct tuning. Photochemical and Photobiological Sciences 14(2), 258 - 269

    Rockwell NC, Lagarias JC and Bhattacharya D (2014) Primary endosymbiosis and the evolution of light and oxygen sensing in photosynthetic eukaryotes. Frontiers of Ecology and Evolution 2, doi:10.3389/fevo.2014.00066

    Duanmu* D, Bachy* C, Sudek S, Wong C-H, Jimenez V, Rockwell NC, Martin SS, Ngan CY, Reistetter E, van Baren MJ, Price DC, Wei C-L, Reyes-Prieto A, Lagarias JC and Worden AZ (2014) Marine algae and land plants share conserved phytochrome signaling systems. Proceedings of the National Academy of Sciences (USA) 111(44), 5827–15832 (*co-first authors)

    Gan F, Zhang S, Rockwell NC, Martin SS, Lagarias JC and Bryant DA (2014) Extensive remodeling of a cyanobacterial photosynthetic apparatus in far-red light. Science 345(6202), 1312-1317

    Chen*, A, Li*, C, Hu*, W, Lau, MY, Lin, H, Rockwell, NC, Martin, SS, Jernstedt, JA Lagarias, JC and Dubcovsky, J (2014) PHYTOCHROME C plays a major role in the acceleration of wheat flowering under long day photoperiod. Proceedings of the National Academy of Sciences (USA) 111(28), 10037-10044 (*co-first authors)

    Rockwell NC, Duanmu D, Martin SS. Bachy C, Price DC, Bhattacharya D, Worden AZ and Lagarias JC Eukaryotic Algal Phytochromes Span the Visible Spectrum (2014) Proceedings of the National Academy of Sciences (USA) 111(10), 3871-3876

    Lim S, Rockwell, NC, Martin, SS, Dallas, JL, Lagarias, JC and Ames, JB (2014) Photoconversion changes bilin chromophore conjugation and protein secondary structure in the violet/orange cyanobacteriochrome NpF2164g3. Photochemical and Photobiological Sciences 13(6), 951-962

    Rockwell, NC, Martin, SS, Gulevich, AG and Lagarias, JC (2014) Conserved phenylalanine residues are required for blue shifting of cyanobacteriochrome photoproducts, Biochemistry 53(19), 3118-3130

    Kim, PW, Rockwell, NC, Martin, SS, Lagarias, JC and Larsen, DS (2014) Dynamic inhomogeneity in the cyanobacterial phytochrome Cph1. Biochemistry 53(17), 2818-2826.

    Hirose Y, Rockwell NC, Martin SS, Narikawa R, Inomata K, Lagarias JC and Ikeuchi M (2013) Green/red cyanobacteriochromes regulate complementary chromatic acclimation via a protochromic photocycle, Proceedings of the National Academy of Sciences (USA) 110(13), 4974-4979

    Duanmu D, Casero D, Dent RM, Gallaher S, Yang W, Rockwell NC, Martin SS, Pellegrini M, Niyogi KK, Merchant SS, Grossman AR and Lagarias JC Retrograde bilin signaling enables Chlamydomonas greening and phototrophic survival. (2013) Proceedings of the National Academy of Sciences (USA) 110, 3621-3626

    Hu W, Franklin KA, Sharrock RA, Jones MA, Harmer SL and Lagarias JC (2013) Unanticipated regulatory roles for Arabidopsis phytochromes revealed by null mutant analysis. Proceedings of the National Academy of Sciences (USA) 110, 1542-1547

    Kim PW, Rockwell NC, Freer LH, Chang CW, Martin SS, Lagarias JC and Larsen DS (2013) Unraveling the primary isomerization dynamics in cyanobacterial phytochrome Cph1 with multi-pulse manipulations. Journal of Physical Chemistry Letters 4, 2605-2609

    Gottlieb SM, Kim PW, Rockwell NC, Hirose Y, Ikeuchi M, Lagarias JC and Larsen DS (2013). Primary photodynamics of the green/red-absorbing photoswitching regulator of the chromatic adaptation E domain from Fremyella diplosiphon. Biochemistry 52, 8198-8208

    Rockwell NC, Martin SS and Lagarias JC (2012) Red/green cyanobacteriochromes: sensors of color and power. Biochemistry 51(48), 9667-9677

    Park E, Park J, Kim J, Nagatani A, Lagarias JC and Choi G (2012) Phytochrome inhibits binding of phytochrome-interacting factors to their target promoters. Plant Journal 72(4), 537-546

    Kim PW, Pan J, Rockwell NC, Chang C-W, Taylor KC, Lagarias JC and Larsen DS (2012) Ultrafast E to Z photoisomerization dynamics of phytochrome Cph1, Chemical Physics Letters 549, 86-92

    Rockwell NC, Martin SS, Gulevich AG and Lagarias JC (2012) Phycoviolobilin formation and spectral tuning in DXCF cyanobacteriochromes, Biochemistry 51(7), 1449-1463

    Rockwell NC, Martin SS, Feoktistova K and Lagarias JC (2011) J.C. Diverse two-cysteine photocycles in phytochromes and cyanobacteriochromes Proceedings of the National Academy of Sciences (USA) 108(29), 11854-11859

    Song J-Y, Cho HS, Cho J-I, Jeon JS, Lagarias JC and Park Y-I (2011) A near ultraviolet cyanobacteriochrome signaling system elicits negative phototaxis in the cyanobacterium Synechocystis sp. PCC 6803. Proceedings of the National Academy of Sciences (USA) 108(26), 10780-10785

    Shang, L, Rockwell, NC, Martin SS and Lagarias, JC (2010) Biliverdin amides reveal roles for propionate side chains in bilin reductase recognition and in holophytochrome assembly and photoconversion. Biochemistry 49(29), 6070-6082

    Rockwell, NC and Lagarias, JC (2010) A brief history of phytochromes. ChemPhysChem 11(6), 1172-1180

    Kohler, AC, Gae, DD, Richley, MA, Stoll, S, Gunn, A, Lim, S, Martin, SS, Doukov, TI, Britt, RD, Ames, JB, Lagarias, JC and Fisher, AJ (2010) Structural basis for hydration dynamics in radical stabilization of bilin reductase mutants. Biochemistry 49(29), 6206-6218