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Primary Faculty

Jian Liu, Ph.D.

Jian Liu, Ph.D.

website

The central theme of my research is to understand how mechanical actions feedback to biochemical pathways in cellular processes, and how such mechanochemical crosstalk among key cellular players governs spatial-temporal regulation and shapes cell functions. I confront these challenges by bringing together theoretical and computational studies, rooted in statistical mechanics, with a diversity of biological experiments. My current research interest spans three cellular processes – cell migration, membrane trafficking, and cell division.

 
Lab Members:
Selected Publications:
Wu ZH, Su MH, Tong CS, Wu M, Liu J. 2018. Membrane shape-mediated wave propagation of cortical protein dynamics. Nature Communications 9(1): 136.  
Wu ZH, Plotnikov S, Moalim A, Waterman C, Liu J. 2017. Two distinct actin networks mediate traction oscillations to confer focal adhesion mechanosensing. Biophysical Journal 112(4): 780-94
Dorn J, Zhang L, Maddox P, Liu J, Maddox A. 2016. A theoretical model of cytokinesis implicates feedback between membrane curvature and cytoskeletal organization in asymmetric cytokinetic furrowing. Molecular Biology of the Cell 27(8): 1286-99
Hu L, Vecchiarelli A, Mizuuchi K, Neuman K, Liu J. 2015. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system. PNAS 2015; 112(51): E7055-64.
Chen J, Liu J. 2014. Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint. Nature Communications 5(9): 4795.
Liu J, Sun YD, Drubin DG, Oster GF. 2009. The mechanochemistry of endocytosis. PLoS Biology 2009; 7(9): e1000204.
Liu J, Desai A, Onuchic JN, Hwa T. 2008. An integrated mechano-biochemical feedback mechanism describes chromosome motility from prometaphase to anaphase in mitosis. PNAS 2008; 105: 13752-13757.

Shigeki Watanabe, Ph.D.

Shigeki Watanabe, Ph.D.

website

Research topic: Cellular and molecular characterizations of rapid changes during synaptic plasticity

Research

Neurons communicate with each other through chemical signals that are released from one nerve terminal (pre-synapse) and received by another (post-synapse). Neurotransmission is fundamental to both mental and physical activities, and it is also essential for the initial wiring and reconfiguration of neural circuits throughout the lifetime of an organism. In addition, defects in neurotransmission play a causative role in neurological disorders. However, our understanding of the process is limited by three main factors: size, speed, and molecular complexity.

Lab Members:
Namesort descending Classification Email Phone
Chengxiu Zhang Research Technologist czhang21@jhmi.edu 410-955-2494
Grant Kusick Student gkusick1@jhmi.edu 410-955-2494
Kie Itoh, Ph.D. Research Technologist kito5@jhmi.edu 410-955-2494
Lauren Bules Student lbules1@jhu.edu 410-955-2494
Quan (Alfred) Gan, Ph.D. Postdoctoral Fellow qgan5@jhmi.edu 410-955-2494
Shuo Li Student sli54@jhu.edu 410-955-2494
Sumana Raychaudhuri, Ph.D. Postdoctoral Fellow sraycha1@jhmi.edu 410-955-2494
Tyler Ogunmowo Student togunmo1@jhmi.edu 410-955-2494
Yuta Imoto, Ph.D. Postdoctoral Fellow yimoto1@jhmi.edu 410-955-2494
Selected Publications:
Watanabe S. and Boucrot E. (2017) Fast and ultrafast endocytosis. Curr Opin Cell Biol. 5;47:64-71.
Topalidou I, Chen PA, Cooper K, Watanabe S, Jorgensen EM, Ailion M. (2017). The NCA-1 and NCA-2 Ion Channels Function Downstream of Gq and Rho To Regulate Locomotion in Caenorhabditis elegans. Genetics May;206(1):265-282.
Watanabe, S. (2015). Slow or fast? A tale of synaptic vesicle recycling. Science, 350, 46-7.
Watanabe, S., T. Trimbuch, M. Camacho-Pérez, B.R. Rost, B. Brokowski, B. Söhl-Kielczynski, A. Felies, M.W. Davis, C. Rosenmund, and E.M. Jorgensen. 2014. Clathrin regenerates synaptic vesicles from edosomes. Nature 515, p228-33,  DOI 10.1038/nature13846. PMCID: PMC4291189.
Watanabe, S., Q. Liu, M.W. Davis , N. Thomas, J. Richards, G. Hollopeter, M. Gu, N.B. Jorgensen and E.M. Jorgensen. 2013. Ultrafast endocytosis at the C. elegans neuromuscular junction.  eLife  2:e00723.  PMCID: PMC3762212.
Gu, M., Q. Liu, S. Watanabe, L. Sun, B. Grant, and E.M. Jorgensen. 2013. AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis. eLife 2, p00190.  PMCID: PMC3591783.
Shao, Z., Watanabe, S., Christensen, R., Jorgensen, E.M., and Colón-Ramos, D.A., (2013). Synapse location during growth depends on glia location, Cell 154, 337-350. PMCID: PMC3808971.
Watanabe, S., B. Rost., M. Camacho, M. W. Davis, B. Söhl-Kielczynski, A. Felies, C. Rosenmund and E.M. Jorgensen. 2013. Ultrafast endocytosis at mouse hippocampal synapses.  Nature. 504, 242-7.  doi: 10.1038/12809. PMCID: PMC3957339.
Watanabe, S., Richards, J., Hollopeter, G., Hobson, R.J., Davis, M.W., and Jorgensen, E.M. 2012. Nano-fEM: protein localization using correlative photo-activated localization microscopy and electron microscopy. Journal of Visual Experiments 3, e3995. doi: 10.3791/3995. PMCID: PMC3566706
Hobson, R.J., Q. Liu, S. Watanabe and E.M. Jorgensen. 2011. Complexin maintains vesicles in the primed state in C. elegans. Current Biology 21, p106-113. PMCID: PMC348763.
Watanabe, S., A. Punge , G. Hollopeter , K.I. Willig, R.J. Hobson  , M.W. Davis , S.W. Hell , and E.M. Jorgensen. 2011. Protein localization in electron micrographs using fluorescence nanoscopy.  Nature Methods 8, p80-84. PMCID: PMC3059187.
Oikonomou, G., Perens, E. A., Lu, Y., Watanabe, S., Jorgensen, E. M., and Shaham, S. (2011). Opposing activities of LIT-1/NLK and DAF-6/patched-related direct sensory compartment morphogenesis in C. elegans. PLoS Biol. 9, e1001121. PMCID: PMC3153439.
Ou, C.-Y., Poon, V. Y., Maeder, C. I., Watanabe, S., Lehrman, E. K., Fu, A. K. Y., Park, M., Fu, W.-Y., Jorgensen, E. M., Ip, N. Y., et al. (2010). Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components. Cell 141, 846–858. PMCID: PMC3168554.
Pellettieri, J., Fitzgerald, P., Watanabe, S., Mancuso, J., Green, D. R., and Sánchez Alvarado, A. (2010). Cell death and tissue remodeling in planarian regeneration. Dev. Biol. 338, 76–85. PMCID: PMC2835816.
Hammarlund, M., Palfreyman, M. T., Watanabe, S., Olsen, S., and Jorgensen, E. M. (2007). Open syntaxin docks synaptic vesicles. PLoS Biol. 5, e198. PMCID: PMC3048763.

Rong Li, Ph.D.

Rong Li, Ph.D.

website

The goal of our research is to understand how eukaryotic cells polarize, divide, move, and vary their genomes to adapt to the changing environment.  We strive for integrated analyses on the systems level that combines whole-cell quantitative observation and mathematical modeling with cutting-edge molecular genetics approaches.

Research

Dysfunction of cellular mechanisms maintaining proteostasis leads to accumulation of misfolded proteins and their aggregates, which often results in debilitating human diseases, such as neurodegenerative diseases (ND). Interestingly, those diseases are also frequently coupled with mitochondrial defects. Although proteostasis and mitochondria are individually studied intensively in the context of ND, the relationship between those two are poorly understood.

Lab Members:
Namesort descending Classification Email Phone
Akshay Narkar Student anarkar1@jhu.edu 443-287-7667
Albert Liu Student aliu53@jhmi.edu 443-287-7667
Alexis Tomaszewski Student atomasz3@jhmi.edu 443-287-7667
Arthur Wang Student ywang401@jhmi.edu 443-287-7667
Blake Johnson Student bjohn134@jhmi.edu 443-287-7667
Devin Mair Student dmair1@jhmi.edu 443-287-7667
Dina Youngblood Administrative Coordinator dyoungb2@jhmi.edu 410-614-7864
Gordon Sun Student gsun13@jhmi.edu 443-287-7667
Haiyang Wang, Ph.D. Postdoctoral Fellow hwang168@jhmi.edu 443-287-7667
Hung-Ji Tsai, Ph.D. Postdoctoral Fellow hjtsai@jhmi.edu 443-287-7667
Jin Zhu, Ph.D. Postdoctoral Fellow jzhu51@jhmi.edu 443-287-7667
Josh McNamara Student mcnamara@jhmi.edu 443-287-7667
Linhao Ruan Student lruan1@jhmi.edu 443-287-7667
Molly Gordon Student mgordo34@jhmi.edu 443-287-7667
Sree Ramachandran Sr. Laboratory Manager sramach5@jhu.edu 443-287-7667
Xi Zhang, Ph.D. Postdoctoral Fellow xzhan141@jhu.edu 443-287-7667
Xing Duan, Ph.D. Postdoctoral Fellow xduan10@jhmi.edu 443-287-7667
Yi Dong Student yi@jhmi.edu 443-287-7667
Selected Publications:
Paul P, Ramachandran S, Xia S, Unruh JR, Conkright-Fincham J, Li R. 2019. Dopamine receptor antagonists as potential therapeutic agents for ADPKD. PLoS One. 2019 May 6;14(5):e0216220. doi: 10.1371/journal.pone.0216220. eCollection 2019  
Tsai H-J, Nelliat AR, Choudhury MI, Kucharavy A, Bradford WD, Cook ME, Kim J, Mair DB, Sun SX, Schatz MC & Li R. 2019. Hypo-osmotic-like stress underlies general cellular defects of aneuploidyNature (2019) https://doi.org/10.1038/s41586-019-1187-2.  
McDonald NALind ALSmith SELi RGould KL. Nanoscale architecture of the Schizosaccharomyces pombecontractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.  
Jin Zhu, Hung-Ji Tsai, Molly R. Gordon, Rong Li. Cellular Stress Associated with Aneuploidy; Dev Cell. 2018 Feb 26;44(4):420-431. doi: 10.1016/j.devcel.2018.02.002.  
Linhao Ruan, Xi Zhang, Rong Li. Recent insights into the cellular and molecular determinants of aging. J Cell Sci. 2018 Feb 2; 131(3). pii: jcs210831. doi: 10.1242/jcs.210831
Pushpendra Singh, Rong Li. Emerging roles for sphingolipids in cellular aging. Curr Genet. 2017 Dec 19. doi: 10.1007/s00294-017-0799-z.   
Mulla WA, Seidel CW, Zhu J, Tsai HJ, Smith SE, Singh P, Bradford WD, McCroskey S, Nelliat AR, Conkright J, Peak A, Malanowski KE, Perera AG, Li R. 2017. Aneuploidy as a cause of impaired chromatin silencing and mating-type specification in budding yeast. Elife. 2017 Aug 25; 6. pii: e27991. doi: 10.7554/eLife.27991.
McDonald NALind ALSmith SELi RGould KL. 2017.  Nanoscale architecture of the Schizosaccharomyces pombe contractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.
Anderson KL, Page C, Swift MF, Suraneni P, Janssen MEW, Pollard TD, Li R, Volkmann N, Hanein D. 2017. Nano-scale actin-network characterization of fibroblast cells lacking functional Arp23 complex. Journal of structural biology, 197 (3) 312-321.
McDonald NALind ALSmith SELi RGould KL. Nanoscale architecture of the Schizosaccharomyces pombecontractile ring. Elife. 2017 Sep 15; 6. pii: e28865. doi: 10.7554/eLife.28865.
Ruan L, Zhou C, Jin E, Kucharavy A, Zhang Y, Wen Z, Florens L, Li R. 2017. Cytosolic proteostasis through importing of misfolded proteins into mitochondriaNature; Mar 16; 543, 443–446; doi:10.1038/nature21695
Potapova TA, Seidel CW, Box AC, Rancati G, Li R. 2016. Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53. Mol Biol Cell. 2016 Oct 15;27(20):3065-3084. Epub 2016 Aug 24.
Wang PS, Chou FS, Ramachandran S, Xia S, Chen HY, Guo F, Suraneni P, Maher B,  Li R. 2016. Crucial Roles of the Arp2/3 Complex during Mammalian Corticogenesis.  Development 2016; Aug 1 143(15): 2741-2752
Swaney KF, Li R. Function and regulation of the Arp2/3 complex during cell migration in diverse environments. Curr Opin Cell Biol. 2016 May 7;42:63-72.
P Vargas, P Maiuri, M Bretou,  P Sáez, P Pierobon, M Maurin, M Chabaud, D Lankar, D Obino, E Terriac, M Raab, H R Thiam,  HR2, T Brocker, S M Kitchen-Goosen, A Alberts, P Sunareni, S  Xia, R Li , R Voituriez, M Piel, A M Lennon-Duménil. Innate Control of Actin Nucleation Determines Two Distinct Migration Behaviours In Dendritic Cells. Nat Cell Bio.  doi: 10.1038/ncb3284.  2015 Dec 7. [Epub ahead of print]
Potapova TA, Unruh JR, Box AC, Bradford WD, Seidel CW, Slaughter BD, Sivagnanam S, Wu Y, Li RKaryotyping human and mouse cells using probes from single-sorted chromosomes and open source software. Biotechniques. 2015 Dec 1;59(6):335-46. doi: 10.2144/000114362. eCollection 2015.
Zhu J, Heinecke D, Mulla W, Bradford WD, Rubinstein B, Box A, Haug JS and Li R.  Single-cell based quantitative assay of chromosome transmission fidelity. G3. 2015;5:1043-56
Chen G, Mulla WA, Kucharavy A, Tsai HJ, Rubinstein B, Conkright J, McCroskey S, Bradford WD, Weems L, Haug JS, Seidel CW, Berman J, Li R. Targeting the Adaptability of Heterogeneous Aneuploids. Cell. 2015;160:771-784. 
Suraneni P, Fogelson B, Rubinstein B, Noguera P, Volkmann N, Hanein D, Mogilner A, Li R. A Mechanism of Leading Edge Protrusion in the absence of Arp2/3 Complex. Mol Biol Cell. 2015;26:901-12. 
Zhou C, Slaughter BD, Unruh JR, Guo F, Yu Z, Mickey K, Narkar A, Ross RT, McClain M, Li R. Organelle-based aggregation and retention of damaged proteins in asymmetrically dividing cells. Cell. 2014;159:530-542.   
Smith SE, Rubinstein B, Mendes Pinto I, Slaughter BD, Unruh JR, Li R. Independence of symmetry breaking on Bem1-mediated autocatalytic activation of Cdc42.  J Cell Biol. 2013;202:1091-1106. 
Li R. The art of choreographing asymmetric cell division. Dev Cell. 2013;25:439-450. 
Yi K, Rubinstein B, Unruh JR, Guo F, Slaughter BD, Li R. Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes. J Cell Biol. 2013;200:567-576. 
Li R, Albertini DF. The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte. Nat Rev Mol Cell Biol.2013;14:141-152. 
Slaughter BD, Unruh JR, Das A, Smith SE, Rubinstein B, Li R. Non-uniform membrane diffusion enables steady-state cell polarization via vesicular trafficking. Nat Commun. 2013;4:1380. 
Pinto IM, Rubinstein B, Kucharavy A, Unruh J, Li R. Actin Depolymerization Drives Actomyosin Ring Contraction during Budding Yeast Cytokinesis. Dev Cell. 2012;22:1247-1260. 
Chen G, Bradford WD, Seidel CW, Li R. Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy. Nature. 2012;482:246-250. 
Das A, Slaughter BD, Unruh JR, Bradford WD, Alexander R, Rubinstein B, Li R. Flippase-mediated phospholipid asymmetry promotes fast Cdc42 recycling in dynamic maintenance of cell polarity. Nat Cell Biol. 2012;14:304-310. 
Suraneni P, Rubinstein B, Unruh JR, Durnin M, Hanein D, Li R. The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration. J Cell Biol. 2012;197:239-251. 
Zhu J, Pavelka N, Bradford WD, Rancati G, Li R. Karyotypic Determinants of Chromosome Instability in Aneuploid Budding Yeast. PLoS Genet. 2012;8:e1002719. 
Zhou C, Slaughter BD, Unruh JR, Eldakak A, Rubinstein B, Li R. Motility and segregation of hsp104-associated protein aggregates in budding yeast. Cell. 2011;147:1186-1196. 
Yi K, Unruh JR, Deng M, Slaughter BD, Rubinstein B, Li R. Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes. Nat Cell Biol. 2011;13:1252-1258. 
Gao JT, Guimera R, Li H, Pinto IM, Sales-Pardo M, Wai SC, Rubinstein B, Li R. Modular coherence of protein dynamics in yeast cell polarity system. Proc Natl Acad Sci U S A. 2011;108:7647-7652. 
Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature. 2010;468:321-325. 
Xia S, Li X, Johnson T, Seidel C, Wallace DP, Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 2010;137:1075-1084. 
Slaughter BD, Das A, Schwartz JW, Rubinstein B, Li R. Dual modes of cdc42 recycling fine-tune polarized morphogenesis. Dev Cell. 2009;17:823-835.   
Rancati G, Pavelka N, Fleharty B, Noll A, Trimble R, Walton K, Perera A, Staehling-Hampton K, Seidel CW, Li R. Aneuploidy Underlies Rapid Adaptive Evolution of Yeast Cells Deprived of a Conserved Cytokinesis Motor. Cell. 2008;135:879-893.  

Katherine (Kathy) Wilson, Ph.D.

Katherine (Kathy) Wilson, Ph.D.

website

Within each human cell is a NUCLEUS, 'mothership' of the human genome and still the least-understood cellular structure. Chromosomes are enclosed by the nuclear envelope (NE) and communicate with the cytoplasm through Nuclear Pore Complexes (NPCs). The inner and outer membranes of the NE are mechanically connected by SUN-domain proteins and nesprins, which form LINC (links the nucleoskeleton and cytoskeleton) complexes. LINC complexes are anchored to nuclear intermediate filament (nuclear ‘lamina’) networks.

Research

The cell nucleus surrounds, organizes and mechanically protects the genome. Lamin filament networks and nuclear membrane proteins support and influence most activities in the nucleus, with central and dynamic roles in customizing the 3D spatial organization of individual chromosomes needed for tissue-specific gene silencing. The functions and regulation of nuclear ‘lamina’ networks are an open frontier in biology.

Selected Publications:
Dharmaraj T and Wilson KL. (2017). How chromosomes unite. Nature 551:568-569.
Florwick A, Dharmaraj T, Jurgens J, Valle D, Wilson KL. 2017.  LMNA sequences of 60,706 unrelated individuals reveal 132 novel missense variants in A-type lamins and suggest a link between variant p.G602S and Type 2 Diabetes.  Jun 15;8:79. doi: 10.3389/fgene.2017.00079. eCollection 2017.
Sonnenberg A and Wilson KL (2016). Preface. Methods Enzymol. 569:xix-xx. [Co-Editor]
Berk JM and Wilson KL. (2016). Simple separation of functionally distinct populations of lamin-binding proteins. Methods Enzymol. 569:101-114.
Mojica SA, Hovis KM, Frieman MB, Tran B, Hsia RC, Ravel J, Jenkins-Houk C, Wilson KL, Bavoil PM (2015) SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors. Molecular Biology of the Cell 26:1918-1934.
Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Gronning-Wang LM, Carlson CR, Wilson KL (2014) The molecular basis of emerin-emerin and emerin-BAF interactions. J. Cell Science 127:3956-3969. 
Bar DZ, Davidovich M, Lamm AT, Zer H, Wilson KL and Gruenbaum Y (2014) BAF-1 mobility is regulated by environmental stresses. Molecular Biology of the Cell 25:1127-36. PMC3967975
Berk JM, Tifft KE and Wilson KL. (2013) The nuclear envelope LEM-domain protein emerin. Nucleus 4:1-17. 
Berk JM, Maitra S, Dawdy AW, Shabanowitz J, Hunt DJ and Wilson KL. (2013) O-GlcNAc regulates emerin binding to BAF in a chromatin- and lamin B-enriched ‘niche’. J. Biological Chemistry 288:30192-209.
Simon DN and Wilson KL. (2013) Partners and posttranslational modifications of nuclear lamins. Chromosoma 122:13-31. 
Wozniak M, Baker BM, Chen C and Wilson KL. (2013) Emerin-binding transcription factor Lmo7 is regulated by association with p130Cas at focal adhesions. PeerJ e134
Simon DN, Domaradzki T, Hofmann WA and Wilson KL. (2013) Lamin A tail modification by SUMO1 is disrupted by familial partial lipodystrophy-causing mutations. Molecular Biology of the Cell 24:342-50.
Barkan R, Zahand AJ, Sarabi K, Lamm AT, Feinstein N, Haithcock E, Wilson KL, Liu J and Gruenbaum Y. (2012) Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function and mitosis. Molecular Biology of the Cell 23:543-552. 
Gjerstorff MF, Rösner HI, Pedersen CB, Greve KB, Schmidt S, Wilson KL, Mollenhauer J, Besir H, Poulsen FM, Møllegaard NE and Ditzel HJ. (2012) GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL). PloS One 7:e45819.
Simon DN and Wilson KL. (2011) The nucleoskeleton as a dynamic genome-associated ‘network of networks.’ Nature Reviews Mol. Cell. Biol. 12:695-708.
Montes de Oca RM, Andreassen PR and Wilson KL. (2011) Barrier to Autointegration Factor influences specific histone modifications. Nucleus 2:580-590. 
Wilson KL and Dawson SC. (2011) Functional evolution of nuclear structure. J Cell Biology 195:171-181.
Wilson KL and Berk JM. (2010) The nuclear envelope at a glance. J Cell Science 123:1973-1978. 
Simon DN, Zastrow MS, Wilson KL. (2010) Direct actin binding to A- and B-type lamin tails and actin filament bundling by the lamin A tail. Nucleus 1:264-272. 
Tifft KE, Bradbury KA and Wilson KL. (2009) Tyrosine phosphorylation of nuclear membrane protein emerin by Src, Abl and other kinases. J Cell Science 122:3780-3790. 
Montes de Oca R, Shoemaker CJ, Gucek M, Cole RN and Wilson KL. (2009) Barrier to Autointegration Factor proteome reveals chromatin-regulatory partners. PLoS One e7050. 
Holaska JM and Wilson KL. (2007) An emerin ‘proteome’: purification of distinct emerin-containing complexes from HeLa cells suggests molecular basis for diverse roles including gene regulation, mRNA splicing, signaling, mechanosensing and nuclear architecture. Biochemistry 46, 8897-908. 
Margalit A, Neufeld E, Feinstein N, Wilson KL, Podbilewicz B and Gruenbaum Y (2007).  Barrier to autointegration factor (BAF) blocks premature cell fusion and maintains adult muscle integrity in C. elegans. J Cell Biology 178:661-673. 
Zastrow MS, Flaherty DB, Benian GM and Wilson KL (2006). Nuclear titin interacts with A- and B-type lamins in vitro and in vivo. J. Cell Science 119:239-249.
Montes de Oca R, Lee KK and Wilson KL (2006). Binding of barrier-to-autointegration factor (BAF) to histone H3 and selected linker histones including H1.1.  J Biological Chemistry 280:42252-62

Hiromi Sesaki, Ph.D.

Hiromi Sesaki, Ph.D.

website

Research Topic:  Mitochondrial Dynamics and Phospholipid Metabolism

Research

Mitochondria play crucial roles in diverse cellular and physiological processes such as energy production, metabolism, intracellular signaling, cell death, development, and immune response. In these functions, mitochondria serve as a bioenergetic power plant and a dynamic signaling hub. It has become increasingly clear that these mitochondrial functions are important for human health, and defects in these processes lead to pathological consequences such as metabolic diseases, cancer, autoimmune diseases, and neurodegenerative diseases.

Lab Members:
Namesort descending Classification Email Phone
Daisuke Murata, Ph.D. Postdoctoral Fellow dmurata1@jhmi.edu 410-502-6842
Kenta Arai, Ph.D. Postdoctoral Fellow karai1@jhmi.edu 410-502-6842
Tatsuya Yamada, Ph.D. Postdoctoral Fellow tyamada6@jhmi.edu 410-502-6842
Yoshihiro Adachi, Ph.D. Postdoctoral Fellow yadachi1@jhmi.edu 410-502-6842
Selected Publications:
Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A, Kato T, Araki Y, Huganir RL, Dawson TM, Yanagawa T, Okamoto K, Iijima M and Sesaki H. (2018). Mitochondrial stasis reveals p62-mediated ubiquitination in parkin-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metabolism. In press.  
Igarashi, A., Itoh, K., Yamada, T., Adachi, Y., kato, T., Murata, D., Sesaki, H., and Iijima, M. (2018).  Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility. J. Biol. Chem. Accepted.  
Nemani N, Carvalho E, Tomar D, Dong Z, Ketschek A, Breves SL, Jaña F, Worth AM, Heffler J, Palaniappan P, Tripathi A, Subbiah R, Riitano MF, Seelam A, Manfred T, Itoh K, Meng S, Sesaki H, Craigen WJ, Rajan S, Shanmughapriya S, Caplan J, Prosser BL, Gill DL, Stathopulos PB, Gallo G, Chan DC, Mishra P, Madesh M. 2018. MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. Cell Rep. 2018 Apr 24;23(4):1005-1019.  
Kwon D, Sesaki H, Kang SJ. 2018. Intracellular calcium is a rheostat for the STING signaling pathway. Biochem Biophys Res Commun. 2018 Jun 2;500(2):497-503. doi: 10.1016/j.bbrc.2018.04.117. Epub 2018 Apr 21.  
Jouroukhin Y, Kageyama Y, Misheneva V, Shevelkin A, Andrabi S, Prandovszky E, Yolken RH, Dawson VL, Dawson TM, Aja S, Sesaki H, Pletnikov MV. 2018. DISC1 regulates lactate metabolism in astrocytes: implications for psychiatric disorders. Transl Psychiatry. 2018 Apr 12;8(1):76. doi: 10.1038/s41398-018-0123-9.  
Roy S, Esmaeilniakooshkghazi A, Patnaik S, Wang Y, George SP, Ahrorov A, Hou JK, Herron AJ, Sesaki H, Khurana S. 2018. Villin-1 and Gelsolin Regulate Changes in Actin Dynamics That Affect Cell Survival Signaling Pathways and Intestinal Inflammation Gastroenterology. 2018 Apr;154(5):1405-1420  
Gajendiran P, Vega LI, Itoh K, Sesaki H, Vakili MR, Lavasanifar A, Hong K, Mezey E, Ganapathy-Kanniappan S. 2018. Elevated mitochondrial activity distinguishes fibrogenic hepatic stellate cells and sensitizes for selective inhibition by mitotropic doxorubicin. J Cell Mol Med. 2018 Apr;22(4):2210-2219. doi: 10.1111/jcmm.13501. Epub 2018 Feb 4.  
Perry HM, Huang L, Wilson RJ, Bajwa A, Sesaki H, Yan Z, Rosin DL, Kashatus DF, Okusa MD. 2018. Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI. J Am Soc Nephrol. 2018 Jan;29(1):194-206  
Kameoka S, Adachi Y, Okamoto K, Iijima M, Sesaki H. 2017. Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics. Trends Cell Biol. [Epub ahead of print].
Gerber S, Charif M, Chevrollier A, Chaumette T, Angebault C, Kane MS, Paris A, Alban J, Quiles M, Delettre C, Bonneau D, Procaccio V, Amati-Bonneau P, Reynier P, Leruez S, Calmon R, Boddaert N, Funalot B, Rio M, Bouccara D, Meunier I, Sesaki H, Kaplan J, Hamel CP, Rozet JM, Lenaers G. 2017. Mutations in DNM1L, as in OPA1, result indominant optic atrophy despite opposite effectson mitochondrial fusion and fission. Brain. 140(10):2586-2596. 
Adachi Y, Itoh K, Iijima M, Sesaki H. 2017. Assay to measure interactions between purified Drp1 and synthetic liposomes. Bio-Protocol. Vol 7, Iss 9.
Santoro A, Campolo M, Liu C, Sesaki H, Meli R, Liu ZW, Kim JD, Diano S. 2017. DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons. Cell Metab. 25(3):647-660.  
Bordt EA, Clerc P, Roelofs BA, Saladino AJ, Tretter L, Adam-Vizi V, Cherok E, Khalil A, Yadava N, Ge SX, Francis TC, Kennedy NW, Picton LK, Kumar T, Uppuluri S, Miller AM, Itoh K, Karbowski M, Sesaki H, Hill RB, Polster BM. 2017. The putative Drp1 inhibitor mdivi-1 Is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species. Dev Cell. 2017;40(6):583-594.
Adachi Y, Iijima M, Sesaki H. An unstructured loop that is critical for interactions of the stalk domain of Drp1 with saturated phosphatidic acid.  2017 Jun 23:1-8. doi: 10.1080/21541248.2017.1321614. [Epub ahead of print]
Pereira R, Tadinada SM, Zasadny FM, Oliveira K, Pires KM, Olvera A, Jeffers J, Souvenir R, Mcglauflin R, Seei A, Funari T, Sesaki H, Potthoff MJ, Adams CM, Anderson EJ, Abel ED. 2017. OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance.  2017 Jun 12. pii: e201696179. doi: 10.15252/embj.201696179. [Epub ahead of print]
Cho B, Cho HM, Jo MY, Kim HD, Song M, Moon C, Kim H, Kim K, Sesaki H, Rhyu IJ, Kim H. Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division.  2017 Jun 9;8:15754. doi: 10.1038/ncomms15754.  
Yamada T, Adachi Y, Yanagawa T, Iijima M, Sesaki H. 2017. p62/sequestosome-1 knockout delays neurodegeneration induced by Drp1 loss. Neurochem Int. 2017 May 18. pii: S0197-0186(17)30189-4. doi: 10.1016/j.neuint.2017.05.012. [Epub ahead of print]
Rohani A, Moore JH, Kashatus JA, Sesaki H, Kashatus DF, Swami NS. Label-Free Quantification of Intracellular Mitochondrial Dynamics Using Dielectrophoresis. Anal Chem. 2017 Jun 6;89(11):5757-5764. doi: 10.1021/acs.analchem.6b04666. Epub 2017 May 15
Rogers MA, Maldonado N, Hutcheson JD, Goettsch C, Goto S, Yamada I, Faits T, Sesaki H, Aikawa M, Aikawa E. 2017. Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress. Circ Res. 121(3):220-233.  
Yang J-M,  Schiapparelli P,  Nguyen H-N, Igarashi A, Zhang Q, Abbadi S, Amzel LM, Sesaki H, Quinones-Hinojosa A and Iijima M. 2017. Characterization of PTEN mutations in brain cancer reveals that PTEN mono-ubiquitination promotes protein stability and nuclear localization. Oncogene. Jun 29;36(26):3673-3685. doi: 10.1038/onc.2016.493. Epub 2017 Mar 6.
Yang X, Wang H, Ni HM, Xiong A, Wang Z, Sesaki H, Ding WX, Yang L. 2017. Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice. Redox Biol. 12:264-273
Salka K, Bhuvanendran S, Wilson K, Bozidis P, Mehta M, Rainey K, Sesaki H, Patterson GH, Jaiswal JK, Colberg-Poley AM. 2017. Superresolution imaging identifies that conventional trafficking pathways are not essential for endoplasmic reticulum to outer mitochondrial membrane protein Transport. Sci Rep. 7 (1):16.
Kwon D, Park E, Sesaki H, Kang SJ. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) suppresses STING-mediated DNA sensing pathway through inducing mitochondrial fission. 2017. Biochem Biophys Res Commun. 493(1):737-743
Yamada T, Adachi Y, Fukaya M, Iijima M, Sesaki H. 2016. Drp1 deficiency leads to Rip3-mediated necroptotic neurodegeneration. Am J Pathol. 186(11):2798-2802.
Manczak M, Kandimalla R, Fry D, Sesaki H, Reddy PH. 2016. Protective Effects of Reduced Dynamin-related Protein 1 Against Amyloid Beta-induced Mitochondrial Dysfunction and Synaptic Damage in Alzheimer's Disease. Hum Mol Genet. 25(23):5148-5166.
Kandimalla R, Manczak M, Fry D, Suneetha Y, Sesaki H, Reddy PH. 2016. Reduced Dynamin-related Protein 1 Protects Against Phosphorylated Tau-induced Mitochondrial Dysfunction and Synaptic Damage in Alzheimer's Disease. Hum Mol Genet. 25(22):4881-4897.
Kojima R, Kajiura S, Sesaki H, Endo T, Tamura Y. 2016. Identification of multi-copy suppressors for ER-mitochondria tethering proteins in Saccharomyces cerevisiae. FEBS Lett. 2016; Epub ahead of print.  
Yamada T, Adachi Y, Fukaya M, Iijima M, Sesaki H. Drp1 deficiency leads to Rip3-mediated necroptotic neurodegeneration. Am J Pathol. 2016; Epub ahead of print
Adachi Y, Itoh K, Yamada T, Cerveny KL, Suzuki TL, Macdonald P, Frohman MA, Ramachandran R, Iijima M, Sesaki H. Coincident phosphatidic acid interaction restrains Drp1 in mitochondrial division. Mol Cell. 2016;63:1034-43.
Xiong ZM, Choi J, Wang K, Zhang H, Tariq Z, Wu D, Ko E, LaDana, C, Sesaki H, Cao K. Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria. Aging Cell. 2016;15:279-290  
Zhang L, Trushin S, Christensen TA, Bachmeier BV, Gateno B, Schroeder A, Yao J, Itoh K, Sesaki H, Poon WW, Gylys KH, Patterson ER, Parisi JE, Diaz Brinton R, Salisbury JL, Trushina E. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease. Sci Rep. 2016;6:18725
Senoo H, Cai H, Wang Y, Sesaki H, Iijima M. The novel racE binding protein GflB sharpens ras activity at the leading edge of migrating cells. Mol Biol Cell. 2016;27(10):1596-605.
Roy M, Itoh K, Iijima M, Sesaki H. Parkin suppresses Drp1-independent mitochondrial division. Biochem Biophys Res Commun. 2016;475(3):283-8.
Khacho M, Clark A, Svoboda DS, Azzi J, MacLaurin JG, Meghaizel C, Sesaki H, Lagace DC, Germain M, Harper M-E, Park DS, Slack RS. 2016. Mitochondrial dynamics impact stem cell identity and fate decisions by regulating a nuclear transcriptional program. Cell Stem Cell. 19(2):232-47.  
Buck MD, O'Sullivan D, Klein Geltink RI, Curtis JD, Chang CH, Sanin DE, Qiu J, Kretz O, Braas D, van der Windt GJ, Chen Q, Huang SC, O'Neill CM, Edelson BT, Pearce EJ, Sesaki H, Huber TB, Rambold AS, Pearce EL. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 2016;Epub ahead of print
Klionsky DJ et al. (~ 2000 authors). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12:1-222
Yamada T, Adachi Y, Iijima M, Sesaki H. Making a division apparatus on mitochondria. Trends Biochem Sci. 2016;41:209-210
Senoo H, Sesaki H, Iijima M. A GPCR handles bacterial sensing in chemotaxis and phagocytosis. Dev Cell. 2016;36:354-356.
Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, Berg-Alonso L, Kageyama Y, Serre V, Moore D, Verschueren A, Rouzier A, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklingerm V. Reply: High prevalence of CHCHD10 mutations in patients with frontotemporal dementia from China. Brain. 2016;Epub ahead of print
Genin EC, Plutino M, Bannwarth S, Villa E, Cisneros-Barroso E, Roy M, Ortega-Vila B, Fragaki K, Lespinasse F, Pinero-Martos E, Augé G, Moore D, Burté F, Lacas-Gervais S, Kageyama Y, Itoh K, Yu-Wai-Man P, Sesaki H, Ricci JE, Vives-Bauza C, Paquis-Flucklinger V. CHCHD10 mutations promote loss of mitochondrial cristae junctions with impaired mitochondrial genome maintenance and inhibition of apoptosis. EMBO Mol Med. 2015;8:58-72
Roy, M., Reddy, P.H., Iijima, M., and Sesaki, H. (2015). Mitochondrial division and fusion in metabolism. Curr. Opin. Cell Biol. 33:111-118
Serasinghe, M.N., Weider, S.Y., Renault, T.T., Elkholi, R., Asciolla, J.J., Yao, J.L., Jabado, O., Hoehn, K., Kageyama, Y., Sesaki, H., and Chipuk, J.E. (2015). Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol. Cell. 57: 521-536.
Li, S., Xu, S., Roelofs, B.A., Boyman, L., Lederer, J.W., Sesaki, H., and Karbowski, M. (2015). Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission. J. Cell Biol. 208: 109-123. 
Kageyama, Y., Hoshijima, M., Seo, K., Bedja, D., Sysa-Shah, P., Andrabi, S., Chen, W., Höke, A., Dawson, V.L., Dawson, T.M., Gabrielson, K., Kass, D.A., Iijima, M., and Sesaki, H. (2014). Parkin-independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain. EMBO J. 33: 2798-2813.
Berthet, A., Margolis, E.B., Zhang, J., Hsieh, I., Zhang, J., Hnasko, T.S., Ahmad, J., Edwards, R.H., Sesaki, H., Huang, E.J., and Nakamura K. (2014). Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons. J. Neurosci. 34: 14304-14317.
Zhang, Q., Tamura, Y., Roy, M., Adachi, Y., and Iijima, M., and Sesaki, H. (2014). Biogenesis and roles of phospholipids in mitochondrial fusion, division and mitophagy. Cell Mol. Life Sci. 71: 3767-3778.
Itoh, K., Tamura, Y., Iijima, M., and Sesaki H. (2013). Effects of Fcj1-Mos1 and mitochondrial division on aggregation of mitochondrial DNA nucleoids and organelle morphology. Mol. Biol. Cell. 24: 1842-1851
Tamura, Y., Harada, Y., Nishikawa, S., Yamano, K., Megumi, K., Shiota, T., Kuroda, T., Kuge, O., Sesaki, H., Imai, K., Tomii, K., and Endo, T. (2013). Tam41 is a novel CDP-diacylglycerol synthase for cardiolipin biosynthesis in mitochondria. Cell Metabolism. 17: 709-18.
Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T.W., Reddy, P.H., Iijima, M. and Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. J. Cell Biol. 197(4):535-51.
Tamura, Y., Onguka, O., Itoh, K., Endo, T., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Phosphatidylethanolamine biosynthesis in mitochondria: phosphatidylserine (PS) trafficking is independent of a PS decarboxylase and intermembrane space proteins, Ups1p and Ups2p.  J. Biol. Chem. 287:43961-43971
Tamura, Y., Onguka, O., Aiken Hobbs, A.E., Jensen, R.E., Iijima, M., Claypool, S.M., and Sesaki, H. (2012). Role for two conserved intermembrane space proteins, Ups1p and Up2p, in intra-mitochondrial phospholipid trafficking. J. Biol. Chem. 287(19):15205-15218.
Tamura, Y., Itoh, K. and Sesaki, H. (2011). SnapShot: Mitochondrial dynamics. Cell. 145:1158-11581e
Zhang, Z., Wakabayashi, N., Wakabayashi, J., Tamura, Y., Song, W.-J., Sereda, S., Clerc, P., Polster, B.M., Aja, S.M., Pletnikov, M.V., Kensler, T.W., Shirihai, O.S.,., Iijima, M., Hussain, M., and Sesaki, H. (2011). The Dynamin-related GTPase Opa1 is required for glucose-stimulated ATP production in pancreatic beta cells. Mol. Biol. Cell. 22: 2235-2245. 
Tamura, Y., Iijima, M., and Sesaki, H. Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation. EMBO J. (2010). 29: 2875-2887.
Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., Kensler, T.W., Iijima, M., and Sesaki, H. (2009). The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 186: 805-816
Tamura, Y., Endo, T., , Iijima, M. and Sesaki, H. (2009). Ups1p and Ups2p antagonistically regulate cardiolipin metabolism in mitochondria. J. Cell Biol. 185: 1029-1045
Cerveny, K.L., Studer, S.L., Jensen, R.E., and Sesaki, H. (2007). Yeast mitochondrial division and distribution requires the cortical Num1 protein. Developmental Cell. 12: 363-375.
Sesaki, H. Dunn, C.D., Iijima, M., Shepard, K.A., Yaffe, M.P., Machamer, C.E., and Jensen, R.E. (2006). Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1p. J. Cell Biol. 173: 651-658. 
Sesaki, H. and Jensen, R.E. (2001). UGO1 encodes an outer membrane protein required for mitochondrial fusion. J Cell Biol. 152:1123-34. 
Sesaki, H. and Jensen, R.E. (1999). Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 147: 699-706. 

Douglas Robinson, Ph.D.

Douglas Robinson, Ph.D.

website

Research Summary

Lab Members:
Namesort descending Classification Email Phone
Amanda Balaban, Ph.D. Postdoctoral Fellow abalaba1@jhu.edu 410-502-4905
Brian Woolums Student bwoolum1@jhu.edu 410-502-3249
Eleana Parajón Student eparajo1@jhu.edu 410-502-4905
Jennifer Nguyen Student jnguye27@jhmi.edu 410-502-4905
Kathleen DiNapoli Student kdinapo1@jhmi.edu 410-502-4905
Laura Murphy Administrative Coordinator lmurph36@jhmi.edu 410-502-4905
Ly Nguyen Student lynguyen1402@jhmi.edu 410-502-4905
Priyanka Kothari Student pkothar6@jhmi.edu 410-502-4905
Shantel Angstadt Student sangsta1@jhmi.edu 410-502-4905
Yinan Liu Student ylin234@jhmi.edu 410-502-4905
Research Associates and Staff:
Name Position title Email Phone
Alexandra Surcel, Ph.D. Research Associate asurcel1@jhmi.edu 410-502-4905
Selected Publications:
Schiffhauer ES, Ren Y, Iglesias V, Kothari P, Iglesias PA, Robinson DN. 2019. Myosin IIB assembly-state determines myosin IIB mechanosensitive dynamics. J. Cell Biol. In press.  
Kothari P, Srivastava V, Aggarwal V, Tchernyshyov I, Van Eyk J, Ha T, and Robinson DN. 2019. Contractility kits promote assembly of the mechanoresponsive cytoskeletal network. J. Cell Sci. 2019; 132(2): 1-12.  
Liu Y and Robinson D. 2018. Recent advances in cytokinesis: Understanding the molecular underpinnings. F1000Research 2018; 7(F1000 Faculty Rev): 1849.  
Thomas DG, Robinson DN. 2017. The fifth sense: Mechanosensory regulation of alpha-actinin-4 and its relevance for cancer metastasis. Sem. Cell Dev. Biol. 2017; 71: 68-74.
Nishida K, Brune KA, Putcha N, Mandke P, O’Neal WK, Shade D, Srivastava V, Wang M, An SS, Drummond MB, Hansel NN, Robinson DN, Sidhaye V.  2017. Cigarette smoke disrupts monolayer integrity by altering epithelial cell-cell adhesion and cortical tension. Am. J. Physiol. – Lung Cell Mol. Physiol. 2017; 313(3): L581-L591.
Miao C, Schiffhauer ES, Okeke E, Robinson DN, Luo T. 2017. Parallel compression is a fast, low-cost assay for the high throughput screening of mechanosensory cytoskeletal proteins in cells. ACS Appl. Mater. Interfaces 2017; 9(34): 28168-28179. ACS Appl. Mater. Interfaces 2017; 9(34): 28168-28179
Duan R, Kim JH, Shilagardi K, Schiffhauer E, Son S, Lee D, Li S, Thomas C, Luo T, Fletcher DA, Robinson DN, Chen EH. Spectrin is mechanoresponsive protein shaping the architecture of intercellular invasion. bioRxiv; DOI: 10.1101/154831  
Surcel A, Schiffhauer ES, Thomas D, Zhu Q, DiNapoli K, Herbig M, Otto O, Guck J, Jaffee E, Iglesias P, Anders R, Robinson DN. Harnessing the adaptive potential of mechanoresponsive proteins to overwhelm pancreatic cancer dissemination and invasion. bioRxiv 190553; doi: https://doi.org/10.1101/190553. 2017
Hamann JC, Surcel A, Chen R, Teragawa C, Albeck JG, Robinson DN, Overholtzer M. Entosis is induced by glucose starvation. Cell Reports. 20(1): 201-210. 2017
Schiffhauer E, Robinson DN. 2017. Mechanochemical signaling directs cell shape change. Biophys. J. 112: 207-214. (Featured article)
Kothari P, Schiffhauer E, Robinson DN. Cytokinesis from nanometers to micrometers and microseconds to minutes. 2017. Methods Cell Biol. 137:307-322.
Ibo M, Srivastava V, Robinson DN, Gagnon Z. Cell blebbing in confined microfluidic environments. PLoS One 2016; 11(10): e0163866.
Bai H, Zhu Q, Surcel A, Luo T, Ren Y, Guan B, Liu Y, Wu N, Joseph NE, Wang T-L, Zhang N, Pan D, Alpini G, Robinson DN, Anders RA. Yes-Associated Protein impacts adherens junction assembly through regulating actin cytoskeleton organization. Am. J. Physiol. – Gastrointest. Liver Phys. 2016; In press.
Srivastava V, Iglesias PA, Robinson DN*. 2016. Cytokinesis: Robust cell shape regulation. Semin. Cell Dev. Biol. 2016; 53:39-44.
Schiffhauer ES, Luo T, Mohan K, Srivastava V, Qian X, Griffis E, Iglesias PA, Robinson DN*. Mechanoaccumulative elements of the mammalian actin cytoskeleton. Curr. Biol. 2016; 26: 1473-1479.
Mackenzie ACL, Kyle DD, McGinnis LA, Lee HJ, Aidana N, Robinson DN, Evans JP. Cortical mechanics and myosin-II abnormalities associated with post-ovulatory aging:  Implications for functional defects in aged eggs. Mol. Hum. Reprod. 2016; 22(6):397-409.
Christianson MS, Gerolstein AL, Lee HJ, Monseur BC, Robinson DN, Evans JP. Effects of inhibition of Ubiquitin C-Terminal Hydrolase L1 (UCH-L1) on sperm incorporation and cortical tension in mouse eggs. Mol. Reprod. Dev. 2016; 83(3): 188-189.
Kim JH, Ren Y, Ng WP, Li S, Son S, Kee Y-S, Zhang S, Zhang G, Fletcher DA, Robinson DN, Chen EH. Mechanical tension drives cell membrane fusion. Dev. Cell 2015; 561-573. 
Srivastava V, Robinson DN. Mechanical stress and network structure drive protein dynamics during cytokinesis. Curr. Biol. 2015; 25(5): 663-670. 
Surcel A, Ng W-P, West-Foyle H, Zhu Q, Ren Y, Avery L, Krenc AK, Meyers D, Rock RS, Anders RA, Freel Meyers C, Robinson DN*. Pharmacological activation of myosin II paralogs to correct cell mechanics defects. Proc. Natl. Acad. Sci. USA 2015; 112(5): 1428-1433. 
Ren Y, West-Foyle H, Surcel A, Miller C, Robinson DN. Genetic suppression of a phosphomimic myosin II identifies system-level factors promoting myosin II cleavage furrow accumulation. Mol. Biol. Cell. 2014; 25: 4150-4165.
Sun Q, Luo T, Ren Y, Shirasawa S, Sasazuki T, Cibas ES, Hodgson L, Robinson DN, Overholtzer M. Competition between human cells by entosis. Cell Res. 2014; 24: 1299-1310.
Luo T, Mohan K, Iglesias PA, Robinson DN. Molecular mechanisms of cellular mechanosensing. Nat. Mater. 2013; 12: 1064-1071.
Kee YS, Ren Y, Dorfman D, Iijima M, Firtel RA, Iglesias PA, Robinson DN. A mechanosensory system governs myosin II accumulation in dividing cells. Mol. Biol. Cell 2012; 23(8): 1510-1523.
Poirier CC, Ng WP, Robinson DN, Iglesias PA. Deconvolution of the cellular force-generating subsystems that govern cytokinesis furrow ingression. PLoS Comp. Biol. 2012; 8(4): e1002467. 
Dickinson D, Robinson DN, Nelson WJ, Weis WI. α-catenin and IQGAP regulate myosin localization to control epithelial tube morphogenesis in Dictyostelium. Dev. Cell 2012; 23: 533-546.
Luo T, Mohan K, Srivastava V, Ren Y, Iglesias PA, Robinson DN. Understanding the cooperative interactions between myosin II and actin crosslinkers mediated by actin filaments during mechanosensation. Biophys. J. 2012; 102(2): 238-247. 
Zhou Q, Kee Y-S, Poirier CC, Jelinek C, Osborne J, Divi S, Surcel A, Tran ME, Eggert US, Müller-Taubenberger A, Iglesias PA, Cotter RJ, Robinson DN. 14-3-3 coordinates microtubules, Rac, and myosin II to control cell mechanics and cytokinesis. Curr. Biol. 2010; 20:1881-1889.
Larson SM, Lee HJ, Hung P-h, Matthews LM, Robinson DN, Evans JP. Cortical mechanics and meiosis II completion in mammalian oocytes are mediated by myosin-II and ezrin-radixin-moesin (ERM) proteins. Mol. Biol. Cell 2010; 21:3182-3192.
Ren Y, Effler JC, Norstrom M, Luo T, Firtel RA, Iglesias PA, Rock, RS, Robinson DN. Mechanosensing through cooperative interactions between myosin-II and the actin crosslinker cortexillin-I. Curr. Biol. 2009; 19(17):1421-1428.
Reichl EM, Ren Y, Morphew MK, Delannoy M, Effler JC, Girard KD, Divi S, Iglesias PA, Kuo SC, Robinson DN.* 2008. Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics. Curr. Biol. 18: 471-480. PMCID: PMC2361134
Effler JC, Kee Y-S, Berk JM, Tran MN, Iglesias PA, Robinson DN.* Mitosis-specific mechanosensing and contractile protein redistribution control cell shape. Curr. Biol. 2006; 16(19):1962-1967. PMCID: PMC2474462
Zhang W., Robinson DN.* Balance of actively generated contractile and resistive forces controls cytokinesis dynamics. Proc. Natl. Acad. Sci. USA 2005; 102(20):7186-7191. PMCID: PMC1129136
Robinson DN*, Spudich JA. Dynacortin, a genetic link between equatorial contractility and global shape control discovered by library complementation of a Dictyostelium cytokinesis mutant. J. Cell Biol. 2000; 150(4):823-838. PMCID: PMC2175282

Susan Michaelis, Ph.D.

Susan Michaelis, Ph.D.

website

Research Topic : Progeria and lamin A processing by the ZMPSTE24 protease; ERAD and cytosolic protein quality control; yeast and mammalian cell biology.

Research

As human longevity increases, understanding the mechanisms that drive aging becomes ever more critical. We study the premature aging disorder Hutchinson Gilford Progeria Syndrome to gain molecular insights into aging, focusing on the nuclear scaffold protein lamin A and its proteolytic processing enzyme ZMPSTE24, since mutations in either can cause progeria.

Lab Members:
Namesort descending Classification Email Phone
Kaitlin Wood Student kwood34@jhmi.edu 410-955-7274
Kamsi Odinammadu Student kodinam1@jhmi.edu 410-955-8286
Otto Mossberg Student otto.mossberg@jhmi.edu 410-955-7274
Research Associates and Staff:
Name Position title Email Phone
Khurts Shilagardi, Ph.D. Research Associate skhurts1@jhmi.edu 410-955-7274
Eric Spear, Ph.D. Research Associate espear3@jhmi.edu 410-955-8286
Selected Publications:
Spear E. D,. Hsu E.-T., Nie L., Carpenter E.P., Hrycyna C.A., and Michaelis S. (2018). ZMPSTE24 Missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or  protein stability.  Disease Models and Mechanism (Under revision)  
Worman, H. J. and Michaelis, S. (2018). Permanently Farnesylated Prelamin A, Progeria and Atherosclerosis.  Circulation (In Press)  
Preston G. M., Guerriero C. J., Metzger M.B., Michaelis S. and Brodsky J.L. 2018. Substrate insolubility dictates Hsp104-dependent endoplasmic reticulum associated degradation.  Mol. Cell 70:242-253 
Ast, T., Michaelis, S., Schuldiner, M.  (2016) The protease Ste24 clears clogged translocons.  Cell 164:103-114
Maurer, M.J., Spear, E.D., Yu, A.T., Lee, E.J., Shahzad, S, and Michaelis, S.  (2016)  Degradation signals for ubiquitin-proteasome dependent cytosolic protein quality control (CytoQC) in yeast. G3:Genes, Genomes, Genetics 6:1853-66, PMC4938640.
Mehmood S., Marcoux J., Gault J., Quigley A., Michaelis S., Young S.G. Carpenter, E.P. and Robinson C.V.  Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24. Nature Chem. 8:1152-1158. PMC 512 3592
Kane, M. S., Linsday, M. E., Judge, D. P., Barrowman, J., Ap Rys, C., Simonson, L., Dietz, H.C., Michaelis, S. (2013) LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. American Journal of Medical Genetics A 161:1599-1611 PMCID: PMC3740161
Snider J., Hanif A., Lee M. E., Jin K., Yu A. R., Graham C., Chuk M., Damjanovic D., Wierzbicka M., Tang P., Balderes D., Wong V., Jessulat, M., Darowski, K.D. San Luis, BJ., Shevelev, I. Sturley S. L., Boone C., Greenblatt J. F., Zhang Z., Paumi C. M., Babu M., Park H.-O., Michaelis S., and I. Stagljar. (2013) Mapping the functional yeast ABC interactome. Nature Chem. Biol. 9:565-72 PMID: 23831759
Michaelis, S. and Hrycyna, C.A. (2013) A protease for the ages. Science 339:1529-30. PMID: 23539586
Barrowman, J., and Michaelis, S. (2013) The Ste24p Protease. In “Handbook of Proteolytic Enzymes,3nd Edition” (N. Rawlings, and G. S. Salvesen, eds.) Academic Press, Oxford, pp.668-676
Michaelis, S. and Hrycyna, C.A. (2013) A protease for the ages. Science 339:1529-30
Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rys, C., Simonson, L., Dietz, H.C., Michaelis, S. (2013) LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. American Journal of Medical Genetics, Part A (In Press).
Michaelis, S. and Barrowman, J. Biogenesis of the Saccharomyces cerevisiae pheromome a-factor; from yeast mating to human disease. (2012) Microbiology and Molecular Biology Reviews 76: 626-651.
Barrowman J., Wiley, P.A., Hudon, S., Hrycyna, C.A. Michaelis, S. (2012) Human ZMPSTE24 disease mutations: residual enzymatic activity correlates with disease severity. Human Molecular Genetics 21:4084-4093.
Barrowman, J., Hamblet, C., Kane M.S., Michaelis, S. (2012) Requirements for efficient proteolytic cleavage of prelamin A by ZMPSTE24. PLoS ONE 7: e32120.
Metzger MB, and Michaelis S. (2009) Analysis of Quality Control Substrates in Distinct Cellular Compartments Reveals a Unique Role for Rpn4p in Tolerating Misfolded Membrane Proteins Mol. Biol. Cell 20:1006-1019.
Barrowman, J., and Michaelis, S. (2009) ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders. Biological Chemistry 390: 761-773.
Nakatsukasa, K., Huyer, G., Michaelis, S., and Brodsky J. L. (2008) Dissecting the ER-Associated Degradation of a Misfolded Polytopic Membrane Protein. Cell 132: 101-112
Hudon, S. E., Coffinier, C., Michaelis, S., Fong, L. G., Young, S. G., and Hrycyna, C. A. (2008) HIV-Protease inhibitors block the enzymatic activity of purified Ste24p. Biochem Biophys Res Comm. 374:365-368
Barrowman, J., Hamblet, C., George, C.M., and Michaelis, S. (2008) Analysis of prelamin A biogenesis reveals the nucleus to be a CaaX processing compartment. Mol. Biol. Cell 12:5398-5408
Metzger, M. B. Maurer, M. J., Dancy, B. M., and Michaelis, S. (2008) Degradation of a cytosolic protein requires ER-associated degradation (ERAD) machinery. J. Biol. Chem. 283:32302-32316
Paumi, C. M., Menendez, J., Arnoldo, A, Engels, K, Iyer, K. R., Thaminy, S, Georgiev, O., Barral Y., *Michaelis, S, and *Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid (iMYTH) Analysis. Molecular Cell 26: 15-25. * Co-corresponding senior authors.
Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., and Michaelis, S. (2005) Inhibiting Farnesylation Reverses the Nuclear Morphology Defect in a HeLa Cell Model for Hutchinson-Gilford Progeria Syndrome, Proc Natl. Acad Sci. USA 102:14416-14421.
Young, S. G. Fong, L., and Michaelis, S.  (2005) Prelamin A, Zmpste24, misshapen cell nuclei, and progeria- new evidence suggesting that protein farnesylation could be important for disease pathogenesis.  Journal of Lipid Research 46:2531-2558.  

Erika Matunis, Ph.D.

Erika Matunis, Ph.D.

website

Research Topic:  Signals Regulating Stem Cell Self-renewal

What are the signals regulating stem cell fate? 

Research

Many adult tissues are renewed from small populations of stem cells, which continually replace differentiated cells lost to damage or age.  Since tissue stem cells are highly dependent on signals from their local microenvironments, or niches, understanding how niches work is important for manipulating regeneration.  To answer this question, the Matunis lab combines genetics, live imaging, and genome-wide approaches to understand how the germline and somatic cells in the testis that create and reside in the testis niche cooperatively ensure a lifetime supply of sperm.

Lab Members:
Namesort descending Classification Email Phone
Kathy Le Student kle16@jhu.edu 410-502-0013
Katie Conlon Student kconlon1@jhmi.edu 410-955-4145
Kevin Yu Student kyu14@jhu.edu 410-502-0013
Miriam Akeju Student makeju1@jhmi.edu 410-502-0013
Research Associates and Staff:
Name Position title Email Phone
Margaret (Maggie) De Cuevas, Ph.D. Research Associate decuevas@jhmi.edu 410-502-0013
Selected Publications:
Greenspan LJ, Matunis EL. 2017. Live Imaging of the Drosophila Testis Stem Cell Niche. Methods Mol Biol. 1463:63-74.
Ma Q, de Cuevas M, Matunis EL. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary. Development. 2016 Mar 1;143(5):754-63. doi: 10.1242/dev.129627. 
Ma Q, de Cuevas M, Matunis EL. 2016. Chinmo is sufficient to induce male fate in somatic cells of the adult Drosophila ovary. Development Mar 1;143(5):754-63. doi: 10.1242/dev.129627. Epub 2016 Jan 25.
Greenspan LJ, de Cuevas M, Matunis E. Genetics of gonadal stem cell renewal. Annu Rev Cell Dev Biol. 2015;31:291-315. doi: 10.1146/annurev-cellbio-100913-013344. 
Hasan, S., Hétié, P., and Matunis, E.L. (2015). Niche signaling promotes stem cell survival in the Drosophila testis via the JAK-STAT target DIAP1. Dev Biol 404, 27-39.
Stine, R.R., Greenspan, L.J., Ramachandran, K.V., and Matunis, E.L. (2014). Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis. PLoS Genet 10, e1004713.
Ma, Q., Wawersik, M., Matunis, EL.  2014.  The Jak-STAT target Chinmo prevents sex transformation of adult stem cells in the Drosophila testis niche. Dev Cell 31, 474-486.  
Li, Y., Ma, Q., Cherry, C.M., and Matunis, E.L. (2014). Steroid signaling promotes stem cell maintenance in the Drosophila testis. Dev Biol 394, 129-141.
Hetie, P., de Cuevas, M. and Matunis, E.  2014.  Conversion of Quiescent Niche Cells to Somatic Stem Cells Causes Ectopic Niche Formation in the Drosophila Testis. Cell Reports 7, 715-721.
Stine RR, Matunis EL.  Stem cell competition: finding balance in the niche.  2013 Aug;23(8):357-64.
Matunis EL, Stine RR, de Cuevas M.  2012.  Recent advances in Drosophila male germline stem cell biology.  Spermatogenesis 2: 137-144.  PMID: 23087833.
Sinden D, Badgett M, Fry J, Jones T, Palmen R, Sheng X, Simmons A, Matunis E, Wawersik M.  2012.  Jak-STAT regulation of cyst stem cell development in the Drosophila testis.  Dev. Biol. 372: 5-16.  PMID: 23010510.
Issigonis M, Matunis E.  2012.  The Drosophila BCL6 homolog Ken and Barbie promotes somatic stem cell self-renewal in the testis niche.  Dev. Biol. 368: 181-92.  PMID: 22580161.
Sheng, X. R., Matunis, E. L.  2011.  Live imaging of the Drosophila spermatogonial stem cell niche reveals novel mechanisms regulating germline stem cell output.  Development 16:3367-3376.
de Cuevas, M., Matunis, E. L.  2011.  The stem cell niche: Lessons from the Drosophila testis.  Development 14:2861-2969.  
Cherry, C.M., Matunis, E.L. 2010.  Epigenetic regulation of stem cell maintenance in the Drosophila testis via the nucleosome remodeling factor NURF.  Cell Stem Cell 6:557-567.
Issigonis, M., Tulina, N., de Cuevas, M., Brawley, C., Sandler, L., Matunis, E. 2009.  JAK-STAT signal inhibition regulates competition within the Drosophila testis stem cell niche.  Science 326:153-6.
Sheng, X.R., Brawley, C.M., Matunis, E.L. 2009.  Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis.  Cell Stem Cell 5:191-203.
Sheng, X.R., Posenau, T., Gumulak-Smith, J.J., Matunis, E., Van Doren, M., Wawersik, M., 2009.  Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis.  Dev. Biol. 334:335-344.
Buszczak, M., Paterno, S., Lighthouse D., Bachman J., Plank J., Owen S., Skora A., Nystul T., Ohlstein B., Allen A., Wilhelm J., Murphy T., Levis B., Matunis. E., Srivali N., Hoskins R., Spradling A.  2007.  The Carnegie protein trap library: a versatile tool for Drosophila developmental studies.  Genetics 175:1501-1531. 
Terry, N.A, Tulina, N., Matunis, E., DiNardo S.  2006.  Novel regulators revealed by profiling Drosophila testis stem cells within their niche.  Dev. Biol. 294:246-257. 
Wawersik, M., Milutinovich, A. Matunis, E., Williams, B. Van Doren, M.  2005.  Somatic control of germline sexual differentiation is mediated by the JAK/STAT pathway. Nature 436:563-567.  
Brawley, C, Matunis, E. 2004. Regeneration of male germline stem cells by spermatogonial dedifferentiation in vivoScience 304:1331-1334.
Tulina, N., Matunis, E. 2001.  Control of Stem cell self-renewal in Drosophila  spermatogenesis by Jak-STAT signaling.  Science 294: 2546-2549.

Carolyn Machamer, Ph.D.

Carolyn Machamer, Ph.D.

website

Research Topic: Golgi complex structure/function; intracellular protein trafficking; intracellular virus assembly; coronaviruses; exocytosis of large cargo

Research

Coronaviruses are enveloped viruses that assemble by budding into the Golgi lumen and then follow the secretory pathway, which is inefficient for such large cargo. These viruses first induce dilation of Golgi cisternae and then modulate the luminal microenvironment to protect virions during their slow trafficking. We are studying the mechanisms by which these perturbations occur to help understand how cells handle other large cargo (e.g. chylomicrons).

Selected Publications:
Sisk, J.M., M.B. Frieman and C.E. Machamer. 2018. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J. Gen. Virol., Mar 20. doi: 10.1099/jgv.0.001047. [Epub ahead of print]
Gilbert, C.E., E. Sztul and C.E. Machamer. 2018. Commonly used trafficking blocks disrupt ARF1 activation and the localization and function of specific Golgi proteins. Molec. Biol. Cell, E17-11-0622. doi: 10.1091/mbc.E17-11-0622. [Epub ahead of print]  
Shao W, Machamer CE, Espenshade PJ. 2016. Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner. J Lipid Res. 57:1564-1573.
Machamer, C.E. 2015. The Golgi complex in stress and death. Front. Neurosci. 9:421. PMCID: PMC4635215    
Westerbeck, J.W. and C.E. Machamer. 2015. A coronavirus E protein is present in two distinct pools with different effects on assembly and the secretory pathway. J. Virol. 2015 Sep;89(18):9313-23.
Damarla, M., Parniari, A.R., Johnston, L., Maredia, H. Serebreni, L., Hamdan, O., Sidhaye, V.K., Shimoda, L.A., Myers, A.C., Crow, M.T., Schmidt, E.P., Machamer, C.E., Gaestei, M. Rane, M.J., Kolb, T.M., Kim, B.S., Damico, R.L., and Hassoun, P.M. (2014) MK2 mediates apoptosis during lung vascular permeability by regulating movement of cleaved caspase 3. Am. J. Respir. Cell Mol. Biol. 50:932-41.
Gilbert, C.E., D.M. Zuckerman, P.L. Currier, and C. E. Machamer. 2014. Three basic residues of intracellular loop 3 of the beta-1 adrenergic receptor are required for golgin-160-dependent trafficking. Int. J. Mol. Sci.15:2929-45.  
Taylor, M.S., T.R. Ruch, P.Y. Hsiao, Y. Hwang, P. Zhang, L. Dai, C.R. Huang, C.E. Berndsen, M.S. Kim, A. Pandey, C. Wolberger, R. Marmorstein, C. Machamer, J.D. Boeke, and P.A. Cole. 2013. Architectural organization of the metabolic regulatory enzyme ghrelin-O-acyltransferease. J. Biol. Chem.288:32212-28. PMCID: PMC3820860.
Sbodio, J.I., B.D. Paul, C.E. Machamer, and S.H. Snyder. 2013. Golgi protein ACBD3 mediates neurotoxicity associated with Huntington’s disease. Cell Reports 4:890-897. PMCID: PMC3801179
Machamer, C.E. 2013. Accommodation of large cargo within Golgi cisternae. Histochem. Cell Biol., 140:261-269.
Chandran, S. and C.E. Machamer. 2012. Inactivation of ceramide transfer protein during proapoptotic stress by Golgi disassembly and caspase cleavage. Biochem. J., 442:391-402.
Ruch, T.R. and C. E. Machamer. 2012. The coronavirus E protein: assembly and beyond.  Viruses 4:363-382. 
Ruch, T.R. and C.E. Machamer. 2012. A single polar residue and distinct membrane topologies impact the function of the infectious bronchitis coronavirus E protein. PLoS Pathogens 8(5):e1002674.
Ruch, T.R. and C.E. Machamer.  2011. The hydrophobic domain of the infectious bronchitis virus E protein alters the host secretory pathway and is important for release of infectious virus.  J. Virol. 85:675-685.
Zuckerman, D.M. S.W. Hicks, G. Charron, H.C. Hang, and C.E. Machamer.  2011.  Differential regulation of two palmitoylation sites in the cytoplasmic tail of the beta-1 adrendergic receptor. J. Biol. Chem. 286:19014-23.
Cohen, J.R., L.D. Lin and C.E. Machamer. 2011.  Identification of a Golgi targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein.  J. Virol. 85:5794-5803.
Chandran, S. and C.E. Machamer. 2010. Golgi organization and stress sensing.  The Golgi apparatus: Structure, Functions and Mechanisms.  (Nova Science, Inc, Hauppauge NY). 
McBride, C.E. and C.E. Machamer.  2010. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein.  Virology 405:139-148.
McBride, C.E. and C.E. Machamer.  2009. A single tyrosine in the SARS coronavirus membrane protein is important for interaction with the spike protein.  J. Virol. 84:1891-1901.
Chandran, S. and C.E. Machamer.  2008.  Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.  Traffic 9:1894-1904.
Hogue, B.G., and C.E. Machamer. 2008. Coronavirus structural proteins and virus assembly. Nidoviruses. Edited by S. Perlman, T. Gallagher, and E. Snijder. (ASM), pp. 179-200.
Sbodio, J.I. and C.E. Machamer.  2007.  Identification of a redox sensitive cysteine residue in GCP60 that regulates its interaction with golgin-160.  J. Biol. Chem 282:29874-29881.
McBride, C.E., J. Li, and C.E. Machamer. 2007. The cytoplasmic tail of the spike protein of the severe acute respiratory syndrome coronavirus contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein. J. Virol., 81:2418-2428.
Hicks, S.W., T.A. Horn, J.M. McCaffery, D.M. Zuckerman,and C.E. Machamer. 2006. Golgin-160 promotes cell surface expression of the beta-1-adrenergic receptor. Traffic 7:1666-1677.

Takanari Inoue, Ph.D.

Takanari Inoue, Ph.D.

website

Research Topic: Synthetic Cell Biology

Research

The Inoue Lab develops molecular tools to visualize and re-program cellular processes, and uses these tools to understand complex signaling networks as well as dynamic subcellular entities. In particular, the Inoue Lab has developed chemically-activated switches and fluorescent sensors to explore the assembly and function of the primary cilium, mechanisms of cell locomotion, and regulation of phagocytosis.

Lab Members:
Namesort descending Classification Email Phone
Abhijit Deb Roy, Ph.D. Postdoctoral Fellow adebroy1@jhmi.edu 443-287-7669
Allen Kim Student akim85@jhmi.edu 443-287-7669
Allister Suarez, Ph.D. Postdoctoral Fellow asuarez4@jhmi.edu 443-287-7669
Di (Helen) Wu Student dwu32@jhu.edu 443-287-7669
Hideaki Matsubayashi, Ph.D. Postdoctoral Fellow hmatsub2@jhmi.edu 443-287-7669
Hideki Nakamura, Ph.D. Postdoctoral Fellow hnakamu2@jhmi.edu 443-287-7669
Jack Mountain Research Technologist jmounta1@jhu.edu 443-287-7669
Kester Coutinho Student kcoutin1@jhmi.edu 443-287-7669
Robert DeRose Research Specialist jderose1@jhmi.edu 443-287-7669
Yuta Nihongaki, Ph.D. Postdoctoral Fellow ynihong1@jhmi.edu 443-287-7669
Selected Publications:
Miao Y, Battacharya S, Banerjee T, Abudaker-Sharif B, Long Y, Inoue T, Iglesias P and Devreotes P. (2019). Wave patterns organize cellular protrusions and control cortical dynamics. Molecular Systems Biology 15(3). DOI 10.15252/msb.20188585| Published online 11.03.2019.
Naoto Takada, Tomoki Naito, Inoue T, Kazuhisa Nakayama, Hiroyuki Takatsu, Hye-Won Shin. “Enhanced phospholipid flipping by P4-ATPase promotes membrane deformation.” 2018. EMBO Reports (in press). 
Cuei-Ling Wang, Yu-Chen Chang, Ya-Chu Chang, Shi-Rong Hong, Chun-Yu Lin, Ning Hsu, Hsiao-Chi Cheng, Yueh-Chen Chiang, Wei-En Huang, Nathan C. Shaner, Rajat Rohatgi, Inoue T, Yu-Chun Lin. (2018).“Spatiotemporal manipulation of ciliary glutamylation reveals its roles in intraciliary trafficking and Hedgehog signaling.”Nature Communications 2018:9:1732:1-13
Nakamura H, Lee AA, Afshar AS, Lin YC, Tanigawa M, Suarez A, Razavi S, DeRose R, Bobb D, Hong W, Gabelli SB, Goutsias J, Inoue T. 2017. Intracellular production of hydrogels and synthetic RNA granules by multivalent molecular interactions. Nature Materials (In press, doi:10.1038/nmat5006)  
Miao Y, Bhattacharya S, Edwards M, Cai H, Inoue T, Iglesias P, Devreotes PN. 2017.  Altering the threshold of an excitable signal transduction network changes cell migratory modes.  Nat Cell Biol 19:329-340.
Phua SC, Chiba S, Suzuki M, Su E, Roberson EC, Pusapati GV, Setou M, Rohatgi R, Reiter JF, Ikegami K, Inoue T. 2017. Dynamic Remodeling of Membrane Composition Drives Cell Cycle through Primary Cilia Excision. Cell 2017;168:264-279
Niu J., Johny M.B., Dick I.E., Inoue T. 2016. Following Optogenetic Dimerizers and Quantitative Prospects. Biophysical Journal 111:1132–1140
Gaus K., Inoue T. 2016. New Biological Frontiers Illuminated by Molecular Sensors and Actuators. Biophysical journal. 2016; 111(6):E01-2.
Meier EL, Razavi S, Inoue T, Goley ED. A novel membrane anchor for FtsZ is linked to cell wall hydrolysis in Caulobacter crescentus. Mol Microbiol. 2016 Jul;101(2):265-80.
Gaus K., Inoue T. 2016. New Biological Frontiers Illuminated by Molecular Sensors and Actuators. Biophysical Journal. 2016;111(6):E01–E02
Coutinho K, Inoue T. 2016. Deconstructing and constructing innate immune functions using molecular sensors and actuators. Proc. SPIE 9871, Sensing and Analysis Technologies for Biomedical and Cognitive Applications 2016, 987102 (May 19, 2016); doi:10.1117/12.2225185 
Antonczak A.K., Mullee L., Wang Y., Comartin D., Inoue T., Pelletier L. and Morrison C.G. 2016. Opposing effects of pericentrin and microcephalin on the pericentriolar material regulate CHK1 activation in the DNA damage response.  30:2003-10. 
Kim AK, DeRose R, Ueno T, Lin B, Komatsu T, Nakamura H, Inoue T. Toward total synthesis of cell function: Reconstituting cell dynamics with synthetic biology. Sci Signal. 2016 Feb 9;9(414). Review.
Phua SC, Lin YC, Inoue T. An intelligent nano-antenna: Primary cilium harnesses TRP channels to decode polymodal stimuli. Cell Calcium. 2015 Oct;58(4):415-22. Review.
Miyamoto T, Rho E, Inoue T. Deconvoluting AMPK dynamics. Oncotarget. 2015 Oct 13;6(31):30431-2.
Garcia-Gonzalo FR, Phua SC, Roberson EC, Garcia G 3rd, Abedin M, Schurmans S, Inoue T, Reiter JF. Phosphoinositides regulate ciliary protein trafficking to modulate hedgedog signaling. Dev Cell. 2015 Aug 24;34(4):400-9.
Nguyen H-N, Yang J-M, Miyamoto T, Itoh K, Rho E, Zhang Q, Inoue T, Devreotes PN, Sesaki H, and Iijima M. 2015. Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN.  Sci Rep Jul 28;5:12600. doi: 10.1038/srep12600. PMCID: PMC4517176.
Miyamoto T., Rho E, Sample V., Akano H., Magari M., Ueno T., Chen M., Tokumitsu H., Zhang J., and Inoue T.* “Compartmentalized AMPK Signaling Illuminated by Genetically Encoded Molecular Sensors and Actuators” (Accepted at Cell Reports)
Lin B., Yin T., Wu Y.I., Inoue T.* and Levchenko A.* “Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration” (Accepted at Nature Communications)
Onuma H, Komatsu T, Arita M, Hanaoka K, Ueno T, Terai T, Nagano T, Inoue T.  2014.  Rapidly rendering cells phagocytic through a cell surface display technique and concurrent Rac activation.  Sci Signal.  Jul 15;7(334):rs4. doi: 10.1126/scisignal.2005123.
Suarez A., Ueno T., Huebner R., McCaffery J.M., and Inoue T.* “Bin/Amphiphysin/Rvs (BAR) family members bend membranes in cells” Scientific Reports 4, 4693 (2014)  
Kobayashi T., Kim S., Lin Y.C., Inoue T., and Dynlacht B.D. “CP110-interacting proteins, Talpid3 and Cep290, play overlapping and distinct roles in cilia assembly.” Journal of Cell Biology 204, 215 (2014) 
Su S., Phua S.C., DeRose R., Chiba S., Narita K., Kalugin P.N., Katada T., Kontani K., Takeda S. and Inoue T. “Genetically encoded calcium indicator illuminates calcium dynamics in cilia.” Nature Methods 10, 1105 (2013)
Thevathasan, J.V., Tan E., Hui Z., Lin Y.C., Li Y., Inoue T. and Fivaz M. “The small GTPase HRas shapes local PI3K signals through positive feedback and regulates persistent membrane extension in migrating fibroblasts.” Molecular Biology of the Cell 24, 2228 (2013)  
Lin Y.C., Niewiadomski P., Lin B., Nakamura H., Phua S.C., Jiao J., Levchenko A., Inoue T., Rohatgi T., and Inoue T. “Chemically-inducible diffusion trap reveals molecular sieve-like barrier at primary cilia“ Nature Chemical Biology 9, 437 (2013)
Lin YC, Liu T-Y, Razavi S. and Inoue T. “Rapidly Reversible Manipulation of Molecular Activities Using Dual Chemical Dimerizers” Angewandte Chemie 52, 6450 (2013)
Thevathasan, J.V., Tan E., Hui Z., Lin Y.C., Li Y., Inoue T. and Fivaz M. “Local positive feedback from PI3K to Ras drives cell polarization and migration” Molecular Biology of the Cell (doi:10.1091/mbc.E12-12-0905)
Miyamoto T., DeRose R., Suarez A., Ueno T., Chen M., Sun T.-p., Wolfgang M.J., Mukherjee C., Meyers D. and Inoue T. “Generation of Intracellular Logic Gates with Two Orthogonal Chemically Inducible Systems” Nature Chemical Biology (Accepted 2012)
Ueno T., Falkenburger B.H., Pohlmeyer C., and Inoue T. “Triggering Actin Comets Versus Membrane Ruffles: Distinctive Effects of Phosphoinositides on Actin Reorganization” ScienceSignaling 4(203), ra87 (2011) (Cover Article)
Umeda N., Ueno T., Pohlmeyer C., Nagano T. and Inoue T. “A photocleavable rapamycin conjugate for spatiotemporal control of small GTPase activity” Journal of American Chemical Society 133(1), 12-14 (2011) Note: “Scientist use light to move molecules within living cells” Science News article in ScienceDaily
Komatsu T., Kukelyansky I., McCaffery J.M., Ueno T., Varela L.C. and Inoue T. “Organelle-Specific, Rapid Induction of Molecular Activities and Membrane Tethering” Nature Methods 7, 206-208 (2010) Note: “Hopkins researchers put proteins right where they want them” Breaking News article in Genetic Engineering and Biotechnology News
Rahdar M., Inoue T., Meyer T., Zhang J., Vazquez F., and Devreotes P.N. “A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN” Proc. Natl. Acad. Sci. U S A. 106(2):480-5 (2009)
Inoue T. and Meyer T. “Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration” PLoS ONE 3(8), e3068 (2008)
Fivaz M., Bandara S., Inoue T. and Meyer T. "Robust neuronal symmetry breaking by Ras-triggered local positive feedback" Current Biology 18, 44-50 (2008)
Suh BC*, Inoue T*, Meyer T, and Hille B. “Rapid chemically-induced changes of PtdIns(4,5)P2 gate KCNQ ion channels” Science 314, 1454-1457 (2006) (*Contributed Equally) Note: “Perspectives” (Science 314, 1402-1403 (2006)), “Editor’s Choice” (Science STKE 364, tw410 (2006)), “Spotlight” (ACS Chem. Biol. 1, 608 (2006)), “Research Highlights” (Nature Methods 4, 7 (2007))
Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, and Meyer T. “PI(3,4,5)P3 and PI(4,5)P2 lipids target Ras, Rho, Arf and Rab GTPases to the plasma membrane” Science 314, 1458-1461 (2006)
Inoue T, Heo WD, Grimley JS, Wandless TJ, and Meyer T. “Inducible translocation strategies to rapidly activate and inhibit small GTPase signaling pathways” Nature Methods 2, 415-418 (2005)
Inoue T, Kikuchi K, Hirose K, Iino M, and Nagano T. “Spatiotemporal Laser Inactivation of Inositol 1,4,5-Trisphosphate Receptors Using Synthetic Small-molecule Probes” Chem. Biol. 10, 503-509 (2003) Note: “Cover art”
Inoue T, Kikuchi K, Hirose K, Iino M, and Nagano T. “Small molecule-based laser inactivation of inositol 1,4,5-trisphosphate receptor” Chem. Biol. 8, 9-15 (2001)

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