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Primary Faculty

Miho Iijima, Ph.D.

Miho Iijima, Ph.D.

website

Research Topic: Lipid Signaling Chemotaxis

Research

Mutations and deletions in the gene encoding phosphatase and tensin homolog (PTEN) deleted from chromosome 10 are associated with many cancers and autism.  After being recruited to the plasma membrane from the cytosol, PTEN dephosphorylates PIP3 to PIP2 and opposes tumorigenic phosphoinositide 3-kinase signaling. Illustrating the importance of the membrane association of PTEN, we recently discovered a new class of cancer- and autism-associated PTEN mutations that specifically interfere with the membrane association.

Lab Members:
Namesort ascending Classification Email Phone
Takashi Kato, Ph.D. Postdoctoral Fellow tkato8@jhmi.edu 410-502-6836
May Wai Student mwai1@jhu.edu 410-502-6836
Research Associates and Staff:
Namesort ascending Position title Email Phone
Hiroshi Senoo, Ph.D. Research Associate hsenoo1@jhmi.edu 410-502-6836
Selected Publications:
Murata D, Arai K, Iijima M, Sesaki H. Mitochondrial Division, Fusion and Degradation. J Biochem. 2020;167:233-241  
Itoh K, Murata D, Kato T, Yamada T, Araki Y, Saito A, Adachi Y, Igarashi A, Li S, Pletnikov M, Huganir RL, Watanabe S, Kamiya A, Iijima M, Sesaki H. Brain-specific Drp1 regulates postsynaptic endocytosis and dendrite formation independently of mitochondrial division. Elife. 2019 Oct 11;8. pii: e44739.  
Adachi Y, Iijima M, Sesaki H. An unstructured loop that is critical for interactions of the stalk domain of Drp1 with saturated phosphatidic acid. Small GTPases. 2018 Nov 2;9(6):472-479.  
Yamada T, Dawson TM, Yanagawa T, Iijima M, Sesaki H. SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019; In press.
Senoo H, Kamimura K, Kimura R, Nakajima A, Sawai S, Sesaki H, Iijima M. Phosphorylated Rho-GDP directly activates mTORC2 Kinase toward AKT through dimerization with Ras-GTP to regulate cell migration. Nature Cell Biology. 2019; Epub ahead of Print  
Kriebel PW, Majumdar R, Jenkins LM, Senoo H, Wang W, Ammu S, Chen S, Narayan K, Iijima M, Parent CA. Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals. J Cell Biol. 2018;217(8):2891-2910.
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 Metab. 2018 Oct 2;28(4):588-604.e5.  
Itoh K, Adachi Y, Yamada T, Suzuki TL, Otomo T, McBride HM, Yoshimori T, Iijima M, Sesaki H. A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane. J Biol Chem. 2018 Jul 27;293(30):11809-11822.
Yamada T, Adachi Y, Yanagawa T, Iijima M, Sesaki H. p62/sequestosome-1 knockout delays neurodegeneration induced by Drp1 loss. Neurochem Int. 2018 Jul;117:77-81
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. 2018 Jun 15;293(24):9292-9300  
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].
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.
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]
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]
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.
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.
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.
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.
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.
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.
Yang J-M, Nguyen H-N, Sesaki H, Devreotes PN, Iijima M. 2015. Engineering PTEN function: Membrane association and activity.  Methods. 2015 May; 0:119-124. PMCID: PMC4388803
Yang JM, Nguyen HN, Sesaki H, Devreotes PN, and Iijima M. 2014.  Engineering PTEN function: Membrane association and activity.  Methods Oct 22. pii: S1046-2023(14)00335-1. doi: 10.1016/j.ymeth.2014.10.018. [Epub ahead of print]. PMID: 25448479
Nguyen, H-N., Yang, J.M., Rahdar, M., Keniry, M., Swaney KF, Parsons, R., Park, B.H., Sesaki, H., Devreotes, P.N. and Iijima, M. 2014.  A new class of cancer-associated PTEN mutations defined by membrane translocation defects.  Oncogene Sept 29;0. Doi: 10.1038/onc.2014.293. [Epub ahead of print].  PMID: 25263454
Nguyen HN, Yang JM, Afkari Y, Park BH, Sesaki HDevreotes PN, and Iijima M.  2014.  Engineering ePTEN, an enhanced PTEN with increased tumor suppressor activities. Proc Natl Acad Sci U S A. Jul 1;111(26):E2684-93. PMID: 24979808
Nguyen, H-N., Afkari, Y., Senoo, H., Sesaki, H., Devreotes, P.N. and Iijima, M. (2013). Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium. Oncogene, Dec. 2. Doi: 10.1038/onc.2013.507. [Epub ahead of print]. PMID:24292679. PMCID: PMC4041858 [Available on 2015/6/2]
Wang, Y., Senoo, H., Sesaki, H. and Iijima, M. Rho GTPases orient gradient sensing in chemotaxis. Proc. Natl. Acad. Sci. USA. (2013). 110: E4723-32.
Chen, C-L., Wang, Y., Sesaki, H., and Iijima, M. Myosin I links PIP3 signaling to remodeling of the actin cytoskeleton in chemotaxis. Science Signaling. (2012). 5: ra10
Tang, M., Iijima, M., Kamimura, Y., Chen, L., Long, Y., and Devreotes, P. Disruption of PKB signaling restores polarity to cells lacking tumor suppressor PTEN. Mol. Biol. Cell. (2011). 22: 437-47.
Wang, Y., Steimle, P.A., Ren, Y., Ross, C.A., Robinson, D.N., Egelhoff, T.T., Sesaki, H., and Iijima, M. Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation. Mol. Biol. Cell. (2011). 22: 2270-2281
Wang, Y., Chen, C-L., and Iijima, M. Signaling mechanisms for chemotaxis. Development Growth and Differentiation (2011). 53: 495-502
Zhang, P., Wang, Y., Sesaki, H. and Iijima, M. Proteomic identification of PtdIns(3,4,5)P3-binding proteins in D. discoideum. Proc. Natl. Acad. Sci. USA. (2010). 107: 11829-11834.
Pramanik, Md K., Iijima, M., Iwadate, Y., and Yumura, S. PTEN is a mechanosensing signal transducer for myosin II localization in Dictyostelium cells. Genes to Cells. (2009). 14: 821-34.
Chen, L., Iijima, M., Tang, M., Landree, M.A. Huang, Y.E., Xiong, Y., Iglesias, P.A., Devreotes, P.N. PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Developmental Cell. Developmental Cell. (2007) 12: 603-614.
Yoshino, R., Morio, T., Yamada, Y., Kuwayama, H., Sameshima, M., Tanaka, Y., Sesaki, H., and Iijima, M. Regulation of ammonia homeostasis by the ammonium transporter AmtA in Dictyostelium Eukaryot Cell. (2007) 6: 2419-2428. 
Somesh, B.P., Vlahou, G., Iijima, M., Insall, R.H., Devreotes, P.N., Rivero, F. RacG regulates morphology, phagocytosis and chemotaxis. Eukaryot Cell. (2006) 5: 1648-1663.
Janetopoulos, C., Borleis, J., Vazquez, F., Iijima, M., and Devreotes, P.N. Temporal and spatial regulation of phosphoinositide signaling mediates cytokinesis. Developmental Cell. (2005) 8: 467-477.
Iijima, M., Huang, Y.E., Luo, H.R., Vazquez, F., Devreotes, P.N. Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis. J. Biol. Chem. (2004) 16: 16606-16613.
Luo, H.R., Huang, Y.E., Chen, J.C., Saiardi, A., Iijima, M., Ye, K., Huang, Y., Nagata, E., Devreotes, P.N., Snyder, S.H. Inositol Pyrophosphates Mediate Chemotaxis in Dictyostelium via Pleckstrin Homology Domain-PtdIns(3,4,5)P3 Interactions. Cell. (2003) 114: 559-572.
Iijima, M., Huang, Y.E., Devreotes, P.N. Temporal and spatial regulation of chemotaxis. Developmental Cell. (2002) 4; 469-478.
Iijima, M. and Devreotes, P. N. 2002. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610 (Cover).

Andrew Ewald, Ph.D.

Andrew Ewald, Ph.D.

website




Research

Research in the Ewald laboratory starts from a simple question: which cells in a breast tumor are the most dangerous to the patient and most responsible for metastatic disease? To answer this question, we developed novel 3D culture assays to allow real-time analysis of invasion. Briefly, we use enzymatic digestion to isolate thousands of “tumor organoids” from each primary tumor. Each organoid is composed of 200-500 epithelial cancer cells and reflects the cellular heterogeneity of the primary tumor.

Lab Members:
Namesort ascending Classification Email Phone
Meagan Haynes Research Specialist meaganmhaynes@gmail.com 410-614-9288
Matthew Dunworth Student matthewdunworth@jhmi.edu 410-614-3382
Junior West, Ph.D. Postdoctoral Fellow jwest38@jhmi.edu 410-614-3382
James McCann, Ph.D. Postdoctoral Fellow jamesmccann@jhu.edu 410-614-3382
Isaac Chan, M.D., Ph.D. Postdoctoral Fellow isaac@jhmi.edu
Eloise Grasset, Ph.D. Postdoctoral Fellow egrasse1@jhmi.edu 410-614-3382
Elodie Henriet, Ph.D. Postdoctoral Fellow ehenrie2@jhmi.edu 410-614-3382
Beza Woldemeskel Student bwoldem1@jhmi.edu 410-614-3382
Andrew Fraser Student afrase14@jhmi.edu 410-614-3382
Selected Publications:
Hasnain Z, Fraser AK, Georgess D, Choi A, Macklin P, Bader JS, Peyton SR, Ewald AJ, Newton PK. OrgDyn: Feature and Model Based Characterization of Spatial and Temporal Organoid Dynamics. Bioinformatics 2020 Feb 24[Online ahead of print]. DOI: 10.1093/bioinformatics/btaa096.
Jiao Z, Cai H, Long Y, Sirka OK, Padmanaban V, Ewald AJ, Devreotes PN (2020). Statin-induced GGPP depletion blocks macropinocytosis and starves cells with oncogenic defects. Proc Natl Acad Sci U S A, 117(8), 4158-4168. doi: 10.1073/pnas.1917938117.  
Padmanaban V, Tsehay Y, Cheung KJ, Ewald AJ, Bader JS. Between-tumor and Within-Tumor Heterogeneity in Invasive Potential. PLOS Comput Biol, 16 (1), e1007464, 2020 Jan 21.    
Georgess D, Padmanaban V, Sirka OK, Coutinho K, Choi A, Frid G, Neumann NM, Inoue T, Ewald AJ. Twist1-induced epithelial dissemination requires Prkd1signaling. Cancer Res, 2020 Jan 15, 80 (2), 204-218. 
Yang J, Duan X, Fraser AK, Choudhury MI, Ewald AJ, Li R, Sun SX. Microscale Pressure Measurements Based on an Immiscible Fluid/Fluid Interface. Sci Rep. 2019 Dec 27;9(1):20044. doi: 10.1038/s41598-019-56573-x.  
Padmanaban V, Suhail Y, Bader JS, Ewald AJ, "E-cadherin suppresses invasion and promotes metastasis in multiple breast cancer models," Accepted in Principle at Nature, 2019.  
Hickey JW, Dong Y, Chung JW, Salathe SF, Pruitt HC, Li X, Chang C, Fraser AK, Bessell CA, Ewald AJ, Gerecht S, Mao HQ, Schneck JP, " Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy," Adv Mater. 2019 Apr 10:e1807359. 
Li L, Knutsdottir H, Hui K, Weiss MJ, He J, Philosophe B, Cameron AM, Wolfgang CL, Pawlik TM, Ghiaur G, Ewald AJ, Mezey E, Bader JS, Selaru FM, "Human primary liver cancer organoids reveal intra-tumor and inter-patient drug response heterogeneity," JCI Insight. 2019 Jan 24;4(2). pii: 121490.    
Liu X, Cheng Y, Wang Z, Abraham J, Wang Z, Ke X, Yan R, Zhang G, Khashab M, Shin EJ, McNamara G, Ewald AJ, Lin DC, Liu Z, Meltzer S, "Modeling Wnt signaling in Barrett's neoplasia using human Barrett's epithelial organoids and CRISPR-Cas9 genome editing," Cancer Lett. 2018 Nov 1;436:109-118.  
Sirka OK, Shamir ER, Ewald AJ, "Myoepithelial cells are a dynamic barrier to epithelial dissemination," Journal of Cell Biology, 2018 Oct 1;217(10):3368-3381.  
Kim DH, Ewald AJ, Park JS, Kshitiz, Kwak M, Gray RS, Su CY, Seo J, An SS, Levchenko A, "Biomechanical interplay between anisotropic re-organization of cells and the surrounding matrix underlies transition to invasive cancer spread", Sci Rep. 2018 Sep 21;8(1):14210.   
Neumann NM, Perrone MC, Veldhuis JH, Huebner RJ, Zhan H, Devreotes PN, Brodland GW, Ewald AJ. 2018. Coordination of Receptor Tyrosine Kinase Signaling and Interfacial Tension Dynamics Drives Radial Intercalation and Tube Elongation. Dev Cell. 2018 Apr 9;45(1):67-82.e6. doi: 10.1016/j.devcel.2018.03.011. PMID: 29634937  
Ewald AJ. 2018. Metastasis inside-out: dissemination of cancer cell clusters with inverted polarity. EMBO J. 2018 Apr 3;37(7). pii: e99144. doi: 10.15252/embj.201899144. Epub 2018 Mar 9. No abstract available. PMID:29523585  
Neumann NM, Perrone MC, Veldhuis JH, Huebner RJ, Zhan H, Devreotes PN, Brodland GW, and Ewald AJ. 2018. Coordination of receptor tyrosine kinase signaling and interfacial tension dynamics drives radial intercalation and tube elongation. Dev Cell Apr 9;45(1):67-82.e6. doi: 10.1016/j.devcel.2018.03.11.  
Scherer PC, Zaccor NW, Neumann NM, Vasavda C, Barrow R, Ewald AJ, Rao F, Sumner CJ, Snyder SH. 2017. TRPV1 is a physiological regulator of μ-opioid receptors. Proc Natl Acad Sci U S A. 2017 Dec 4. pii: 201717005. doi: 10.1073/pnas.1717005114. [Epub ahead of print]
Asrani K, Sood A, Torres A, Georgess D, Phatak P, Kaur H, Dubin A, Talbot CC Jr, Elhelu L, Ewald AJ, Xiao B, Worley P, Lotan TL. 2017. mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation. J Clin Invest. 2017 Nov 1;127(11):4001-4017. doi: 10.1172/JCI92893. Epub 2017 Sep 25.
Yochum ZA, Cades J, Mazzacurati L, Neumann NM, Khetarpal SK, Chatterjee S, Wang H, Attar MA, Huang EH, Chatley SN, Nugent K, Somasundaram A, Engh JA, Ewald AJ, Cho YJ, Rudin CM, Tran PT, Burns TF. 2017. A First-in-Class TWIST1 Inhibitor with Activity in Oncogene-Driven Lung Cancer. Mol Cancer Res. 2017 Dec;15(12):1764-1776. doi: 10.1158/1541-7786.MCR-17-0298. Epub 2017 Aug 29.
Nguyen-Ngoc KV, Silvestri VL, Georgess D, Fairchild AN, Ewald AJ. 2017. Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation. J Cell Sci. 2017 Oct 1;130(19):3213-3221. doi: 10.1242/jcs.208546. Epub 2017 Aug 18.
Xian L, Georgess D, Huso T, Cope L, Belton A, Chang YT, Kuang W, Zhang X, Senger S, Fassano A, Huso DL, Ewald AJ, Resar LMS. 2017. HMGA1 Amplifies Wnt Signaling and Expands the Intestinal Stem Cell Compartment and Paneth Cell Niche. Nat Communications, 2017 Apr 28;8:15008
Ewald AJ. 2017. Pulling cells out of tumors. Nat Cell Biol. 2017 Mar 1;19(3):147-149. 
Lindberg OR, McKinney A, Engler JR, Koshkakaryan G, Gong H, Robinson AE, Ewald AJ, Huillard E, James CD, Molinaro AM, Shieh JT, Phillips JJ. 2016. GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity. Oncotarget. 2016 Nov 29; 7(48):79101-79116
Teo WW, Merino V, Cho S, Korangath P, Liang X, Wu R, Neumann NM, Ewald AJ, Sukumar S. 2016.  HOXA5, a regulator of cell fate transition, impedes tumor initiation and progression in breast cancer. Oncogene. 2016 Oct 20; 35(42):5539-5551. 
Shamir ER, Coutinho K, Auer M, Ewald AJ. 2016. Twist1+ epithelial cells retain adhesive and proliferative capacity during dissemination. Biol Open. 2016 Sep 15; 5 (9):1216-1228. 
Cheung KJ, Ewald AJ, "A collective route to metastasis: Seeding by tumor cell clusters," Science. 2016 Apr 8;352(6282):167-9.
Huebner RJ, Neumann NM, Ewald AJ, "Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration," 2016, Feb 2, Development.
Ellison D, Mugler A, Brennan M, Lee SH, Huebner RJ, Shamir ER, Woo LA, Kim J, Amar P, Nemenman I, Ewald AJ, Levchenko A, “Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis”, 2016, Jan 20, PNAS
Cheung KJ, Padmanaban VP, Silvestri V, Schipper K, Cohen JD, Fairchild AN, Gorin MA, Verdone JE, Pienta KJ, Ewald AJ, “Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters,” 2016, Feb 1, PNAS.
Ewald AJ, "An arresting story about basement membrane invasion," Dev Cell. 2015 Oct 26;35(2):143-4
Kim M, Shewan A, Ewald AJ, Werb Z, Mostov KE, “P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway,” J Cell Sci. 2015 Oct 19.
Shamir ER and Ewald AJ, “Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration,” Curr Top Dev Biol. 2015;112:353-82.
Chapiro J, Sur S, Savic LJ, Ganapathy-Kniappan S, Reyes J, Duran R, Chettiar-Thiruganasambandam S, Moats CR, Lin M, Luo W, Tran PT, Herman JM, Semenza GL, Ewald AJ, Vogelstein B, Geschwind JF, “Systemic delivery of microencapsulated 2-bromopyruvate for the therapy of pancreatic cancer, Clinical Cancer Research 2014 Dec 15;20(24):6406-17.
Cheung KJ and Ewald AJ, “Illuminating breast cancer invasion: diverse roles for cell-cell interactions”, Current Opinion in Cell Biology, 2014, Oct; 30:99-111.
Bryant DM, Roignot J, Datta A, Orvereem A, Kim M, Yu W, Peng X, Eastburn D, Ewald AJ, Werb Z, and Mostov K, “A molecular switch for the orientation of epithelial cell polarization,” Dev Cell, 2014 Oct 27;31(2):171-87.
Shamir ER and Ewald AJ, “3D Organotypic Culture: Experimental Models of Mammalian Biology and Disease,” Nature Reviews Molecular Cell Biology, 2014 Oct;15(10):647-64.
Huebner RJ, Lechler T, Ewald AJ, “Mammary epithelial stratification occurs through symmetry breaking vertical divisions of luminal cells,” Development. 2014 Mar;141(5):1085-94
Shamir ER, Papallardo E, Jorgens DM, Coutinho K, Tsai WT, Aziz K, Auer M, Tran PT, Bader JS, Ewald AJ, “Twist1-induced dissemination preserves epithelial identity and requires E-cadherin,” JCB 2014 Mar 3;204(5):839-56 (Selected for cover). 
Chen Q, Zhang N, Gray RS, Li H, Ewald AJ, Zahnow CA, and Pan DJ, “A temporal requirement for Hippo signaling in mammary gland differentiation, growth and tumorigenesis”, Genes Dev. 2014 Mar 1;28(5):432-7.
Cheung KJ, Gabrielson, E, Werb Z, Ewald AJ, “Collective invasion in breast cancer requires a conserved basal epithelial program,” Cell, 2013 Dec;155(7):1639-51.
Beck JN, Singh A, Rothenberg AR, Elisseeff JH, Ewald AJ, The independent roles of mechanical, structural and adhesion characteristics of 3D hydrogels on the regulation of cancer invasion and dissemination, Biomaterials, 2013 Dec;34(37):9486-95.  
Nguyen-Ngoc KV and Ewald AJ, “Mammary epithelial elongation and myoepithelial migration are regulated by the composition of the extracellular matrix,” J Microsc. 2013 Sep;251(3):212-23.
Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC, Yaswen P, Werb Z, Ewald AJ, “The ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium” Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):E2595-604. PMC3465416.  
Ewald AJ, Huebner RJ, Palsdottir H, Lee JK, Perez MJ, Jorgens DM, Tauscher AN, Cheung KJ, Werb Z, Auer M, "Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium", J Cell Sci. 2012 Jun 1;125(Pt 11):2638-54. PMC3403234.
Egeblad* M, Ewald* AJ, Asketraud HA, Truitt M, Welm B, Bainbridge E, Peeters G, Krummel M, Werb Z, “Imaging stromal cells in different tumor microenvironments by spinning disk confocal microscopy”, Disease Models and Mechanisms. 2008 Sep/Oct; 1(2/3): 155-67. * = Co-First Authors. PMC2562195
Ewald, AJ, Brenot, A, Duong, M, Chan, BC, Werb, Z. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Developmental Cell, 2008 Apr; 14(4): 570-81.

Peter Espenshade, Ph.D.

Peter Espenshade, Ph.D.

website
Lab Members:
Namesort ascending Classification Email Phone
Stephanie Myers, DVM Student smyers40@jhmi.edu 443-287-5027
Shan Zhao Research Technologist szhao6@jhmi.edu 443-287-5027
Chune Liu, Ph.D. Postdoctoral Fellow cliu117@jhmi.edu 443-287-5027
Chiaki Ishida, Ph.D. Postdoctoral Fellow cishida1@jhmi.edu 443-287-5027
Research Associates and Staff:
Selected Publications:
Gutiérrez MS, Campusano S, González AM, Gómez M, Barahona S, Sepúlveda D, Espenshade PJ, Fernández-Lobato M, Baeza M, Cifuentes V, Alcaíno J. Sterol Regulatory Element-Binding Protein (Sre1) Promotes the Synthesis of Carotenoids and Sterols in Xanthophyllomyces dendrorhous. Front Microbiol. 2019 Mar 29;10:586. doi: 10.3389/fmicb.2019.00586. eCollection 2019.  
Burr R, Stewart EV, Espenshade PJ. 2017. Coordinate regulation of yeast Sterol Regulatory Element-binding Protein (SREBP) and Mga2 transcription factors. J. Biol. Chem. 292:5311-5324. PMCID: PMC5392677
Hwang J, Ribbens D, Raychaudhuri S, Cairns L, Gu H, Frost A, Urban S, Espenshade PJ. 2016. A Golgi rhomboid protease Rbd2 recruits Cdc48 to cleave yeast SREBP. EMBO J. 35:2332-2349. PMCID: PMC5090219
Gong X, Qian H, Shao W, Li J, Wu J, Li W, Espenshade PJ*, Nieng Y*. 2016. Complex structure of the fission yeast SREBP-SCAP binding domains reveals an oligomeric organization. Cell Res. 26:1197-1211. *Corresponding authors. PMCID: PMC5099872
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.
Burr R, Stewart EV, Shao W, Zhao S, Hannibal-Bach HK, Ejsing CS, Espenshade PJ. 2016. Mga2 Transcription Factor Regulates an Oxygen-responsive Lipid Homeostasis Pathway in Fission Yeast. J Biol Chem. 2016 Jun 3;291(23):12171-83. doi: 10.1074/jbc.M116.723650. Epub 2016 Apr 6.
Shao W, Espenshade PJ. 2015. Sugar Makes Fat by Talking to SCAP. Cancer Cell. 2015 Nov 9;28(5):548-9. doi: 10.1016/j.ccell.2015.10.011.
Raychaudhuri s, Espenshade PJ. 2015. Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity. J. Biol. Chem. 290:14430-40.
Gong X, Li J, Shao W, Wu J, Qian H, Ren R, Espenshade PJ*, Nieng Y*. 2015. Crystal structure of the WD40 domain of SCAP from fission yeast reveals the molecular basis for SREBP recognition. Cell Research 25:401-11. PMCID: PMC4387560  
Tong Z, Kim MS, Pandey A, Espenshade PJ. 2014. Identification of candidate substrates for the Golgi Tul1 E3 ligase using quantitative diGly proteomics in yeast. Mol. Cell Proteomics 13:2871-82. PMCID: PMC4223478
Shao W, Espenshade PJ. 2014. Sterol Regulatory Element-binding Protein (SREBP) cleavage regulates Golgi-to-Endoplasmic Reticulum recycling of SREBP Cleavage-activating Protein (SCAP). J. Biol. Chem. 289:7547-7557.
Brookheart RT, Lee CY, Espenshade PJ. 2014. Casein kinase 1 regulates sterol regulatory element- binding protein (SREBP) to control sterol homeostasis. J. Biol. Chem. 289:2725-2735.
Lloyd SJ, Raychaudhuri S, Espenshade PJ. 2013. Subunit architecture of the Golgi Dsc E3 ligase required for Sterol Regulatory Element-Binding Protein (SREBP) cleavage in fission yeast. J. Biol. Chem. 288:21043-54.
Cheung R, Espenshade PJ. 2013. Structural requirements for Sterol Regulatory Element- Binding Protein (SREBP) cleavage in fission yeast. J. Biol. Chem. 288:20351-60.
Espenshade PJ. 2013. Cholesterol Synthesis and Regulation. In: Lennarz, W.J. and Lane, M.D. (eds.) The Encyclopedia of Biological Chemistry, Vol. 3, pp. 516-520. Waltham, MA: Academic Press.
Porter JR, Lee CSY, Espenshade PJ, Iglesias PA. 2012. Regulation of SREBP during hypoxia requires Ofd1-mediated control of both DNA binding and degradation. Mol. Biol. Cell 23:3764-3774.
Shao W, Espenshade PJ. 2012. Expanding roles for SREBP in metabolism. Cell Met. 16:414-419.
Ryan CJ, Roguev A, Patrick K, Xu J, Jahari H, Tong Z, Beltrao P, Shales M, Qu H, Collins SR, Kliegman, JI, Jiang L, Kuo D, Tosti E, Kim H, Edelmann W, Keogh M, Greene D, Tang C, Cunningham P, Shokat KM, Cagney G, Svensson JP, Guthrie C, Espenshade PJ, Ideker T, Krogan NJ. 2012. Hierarchical modularity and the evolution of genetic interactomes across species. Mol. Cell. 46:691-704.
Stewart EV, Lloyd SJ, Burg JS, Nwosu CC, Lintner RE, Daza R, Russ C, Ponchner K, Nusbaum C, Espenshade PJ. 2011. Yeast SREBP cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase. J. Biol. Chem. 287:672-81.
Lee CSY, Yeh TL, Hughes BT, Espenshade PJ. 2011. Regulation of the Sre1 hypoxic transcription factor by oxygen-dependent control of DNA binding. Mol. Cell 44:225-234.
Burg JS, Espenshade PJ. 2011. Glucose controls phosphoregulation of HMG-COA reductase through the PP2A-related phosphatase Ppe1 and Insig in fission yeast. J. Biol. Chem. 286:27139-46.
Stewart EV, Nwosu CC, Tong Z, Roguev A, Cummins TD, Kim DU, Hayles J, Park HO, Hoe KL, Powell DW, Krogan NJ, Espenshade PJ. 2011. Yeast SREBP cleavage activation requires the Golgi Dsc E3 ligase complex. Mol. Cell 42:160-171.
Porter JR, Burg JS, Espenshade PJ, Iglesias PA. 2010. Ergosterol regulates SREBP cleavage in fission yeast. J. Biol. Chem. 285:41051-61.
Bien CM and Espenshade PJ. 2010. SREBP in fungi - Hypoxic transcription factors linked to pathogenesis. Eukaryotic Cell 9:352-9.
Bien CM, Chang YC, Nes WD, Kwon-Chung KJ, and Espenshade PJ. 2009. C. neoformans Site-2 protease is required for virulence and survival in the presence of azole drugs. Mol. Microbiol. 74:672-690.
Lee CY, Stewart EV, Hughes BT and Espenshade PJ. 2009. Oxygen-dependent binding of Nro1 to the prolyl hydroxylase Ofd1 regulates SREBP degradation in yeast. EMBO J. 28:135-43.
Burg JS, Powell DW, Chai R, Hughes AL, Link AJ and Espenshade PJ. 2008. Insig regulates HMG-CoA reductase by controlling enzyme phosphorylation in fission yeast. Cell Metabolism 8:522-31.
Hughes BT and Espenshade PJ. 2008. Oxygen-regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member. EMBO J. 27:1491-1501.
Hughes AL, Todd BL, Espenshade PJ. 2005. SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell 120:831-842.

Deborah Andrew, Ph.D.

Deborah Andrew, Ph.D.

website




Research

Infective parasites must traverse the mosquito salivary glands to transmit malaria to humans and other animals.  The Andrew Lab is leveraging its findings on the molecules required to form and maintain the Drosophila salivary gland to develop strategies to block malaria transmission.  Shown is an optical section through the distal lateral lobe of a female adult salivary gland stained with DAPI (blue, nuclei), alpha-tubulin (green, cytosol) and wheat-germ agglutinin (red; chitin/O-GlcNAcylated proteins).

Research Associates and Staff:
Namesort ascending Position title Email Phone
Rajprasad Loganathan, Ph.D. Research Associate rlogana2@jhmi.edu 410-614-2645
Michael Wells, Ph.D. Research Associate mwells24@jhmi.edu 410-614-2645
JiHoon Kim, Ph.D. Research Associate jkim100@jhmi.edu 410-614-2645
Selected Publications:
Wells, M.B. and Andrew, D.J. (2019) The architecture of the Anopheles stephensi salivary gland presents major barriers to transmission of the malaria parasite Plasmodium berghei.  MBio. In press.
Johnson, D.M. and Andrew, D.J. (2019) Role of tbc1 in Drosophila embryonic salivary glands.  BMC Cell and Molec. Biol  20:19  
Andrew, D.J., Chen, E.H., Manoli, D.S., Ryner, L.C. and Arbeitman, M.N. (2019) Sex and the single fly: A perspective on the career of Bruce S. Baker. Genetics 212(2) 365-376
Manning, L., Sheth, J., Bridges, S., Saadin, A., Odinammadu, K., Andrew, D., Spencer, S., Montell, D. and Starz-Gaiano, M. (2017) A hormonal cue promotes timely follicle cell migration by modulating transcription profiles. Mech. Dev. 148: 56-68.  
Wells MB, Villamor J, and Andrew DJ. Salivary gland maturation and duct formation in the African malaria mosquito Anopheles gambiae. 2017. Scientific Reports 7:601. DOI: 10.1038/s41598-017-00672-0.
Chung S, Kim S, and Andrew DJ. 2017. Uncoupling apical constriction from tissue invagination. Elife Mar6;6. pii: e22235. doi: 10.7554/eLife.22235. PMCID: PMC5338918
Hanlon CD, Andrew DJ. Drosophila FoxL1 non-autonomously coordinates organ placement during embryonic development. 2016. Dev Biol. 2016 Nov 15;419(2):273-284. doi: 10.1016/j.ydbio.2016.09.007. Epub 2016 Sep 13.
Loganathan R, Lee JS, Wells MB, Grevengood E, Slattery M, Andrew DJ. Ribbon regulates morphogenesis of the Drosophila embryonic salivary gland through transcriptional activation and repression. Dev Biol. 2016 Jan 1;409(1):234-50
Wells, M.B. and Andrew, D.J. (2015) Salivary gland cellular architecture in the Asian malaria vector mosquito Anopheles stephensi.  Parasites and Vectors. 8:617. doi: 10.1186/s13071-015-1229-z
Cheng, Y.L. and Andrew, D.J. (2015) Extracellular Mipp1 activity confers migratory advantage to epithelial cells during collective migration. Cell Reports.  Published online November 25, 2015.
Hanlon, C.D. and Andrew, D.J. (2015) Outside-in signaling - a brief review of GPCR signaling with a focus on the Drosophila GPCR family. J Cell Sci 128: 3533-3542. PMID:  26345366.
Fox, R.M. and Andrew, D.J. (2015) Transcriptional regulation of secretory capacity by bZip transcription factors.  Front Biol 10: 28-51.  PMID:  25821458
Loganathan, R., Cheng, Y.L. and Andrew, D.J. (2015) ­Development of the Drosophila Respiratory System.  In:  Organogenetics.  Springer.  In press.
Andrew, D.J. and Yelon, D. (2015) Developmental mechanisms, patterning and organogenesisis. Curr Opin Genet Dev. Epub 2015 Jun 4.
Chung, S.-Y. and Andrew, D.J. (2014) Cadherin 99C regulates apical expansion and cell rearrangement during epithelial tube elongation. Development 141:1950-1960. PMID: 24718992
Fox, R.M., Vaishnavi, A., Maruyama, R., and Andrew, D.J. (2013) Organ-specific gene expression: the bHLH protein Sage provides tissue-specificity to Drosophila FoxA. Development. 140 (10): 2160-2171. PMID: 23578928. 
Barbosa S, Fasanella G, Carreira S, Llarena M, Fox R, Barreca C, Andrew D, O'Hare P. 2013 An orchestrated program regulating secretory pathway genes and cargos by the transmembrane transcription factor CREB-H. Traffic. 2013 Apr;14(4):382-98. doi: 10.1111/tra.12038.
Ismat, A., Cheshire, A. and Andrew, D.J. (2013) The secreted AdamTS-A metalloprotease is required for collective cell migration. Development. 140 (9): 1981-93. doi: 10.1242/dev.087908. Epub 2013 Mar 27. PMID: 23536567.
Maruyama, R., Grevengoed, E., Stempniewicz, P., Andrew, D.J. (2011) Genome-wide analysis reveals a major role in cell fate maintenance and an unexpected role in endoreduplication for the Drosophila FoxA gene fork headPLoS One 6(6): e20901. PMID: 21698206
Chung, S.-Y., Chavez, C. and Andrew, D.J. (2011) Trachealess (Trh) regulates all tracheal genes during Drosophila embryogenesis. Developmental Biology 360: 160-172. PMID: 21963537
Andrew, DJ and Ewald, AJ, “Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration”, Developmental Biology, 2010 May 1;341(1):34-55.
Fox, R.M., Hanlon, C.D. and Andrew, D.J. (2010) The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity. Journal of Cell Biology 191: 479-492. PMID: 21041443
Chung, S.-Y., Vining, M.S., Bradley, P.L., Chan, C.-C., Wharton, K.A. and Andrew, D.J. (2009) Serrano (Sano) functions with the planar cell polarity genes to control tracheal tube length. PLoS Genetics 5(11): e1000746. PMID: 19956736.
Kerman, B.E., Cheshire, A.M., Myat, M.M., and Andrew, D.J. (2008) Ribbon modulates apical membrane during tube elongation through Crumbs and Moesin.  Developmental Biology 320:  278-288. PMID: 18585700
Abrams, E.W., Mihoulides, W.K. and Andrew, D.J. (2006) Fork head and Sage maintain a uniform and patent salivary gland lumen through regulation of two downstream target genes, PH4áSG1 and PH4áSG2. Development 133: 3517-3527. PMID: 16914497.
Abrams, E.W. and Andrew, D.J. (2005) CrebA regulates secretory activity in the salivary gland and epidermis.  Development 132: 2743-2758. PMID: 15901661
Bradley, P.L., Myat, M.M., Comeaux, C. and Andrew, D.J. (2003) Posterior migration of the salivary gland requires an intact visceral mesoderm and integrin function.  Developmental Biology 257:  249-262. PMID: 12729556
Myat, M.M. and Andrew, D.J. (2002) Epithelial tube morphology is determined by the polarized growth and delivery of apical membrane. Cell 111:879-891. PMID: 12526813.
Bradley, P.L. and Andrew, D.J. (2001) ribbon encodes a BTB-containing transcription factor required for directed cell migration.  Development 128: 3001-3015. PMID: 11532922
Myat, M.M. and Andrew, D.J. (2000) Organ shape in the Drosophila salivary gland is controlled by regulated, sequential internalization of the primordia.  Development 127: 679-691. PMID: 10648227
Myat, M.M. and Andrew, D.J. (2000) FORK HEAD prevents apoptosis and promotes cell shape change during formation of the Drosophila salivary glands.  Development 127: 4217-4226. PMID: 10976053
Isaac, D.D. and Andrew, D.J. (1996) Tubulogenesis in Drosophila:  A requirement for the trachealess gene product.  Genes and Development 10: 103-117. PMID: 8557189
Bhanot, P., Brink, M., Samos, C.H., Hsieh, J.-C., Wang, Y., Macke, J.P., Andrew, D., Nathans, J., and Nusse, R. (1996) Dfz2, a new member of the frizzled family in Drosophila, functions as a receptor for Wingless.  Nature 382: 225-230.  PMID: 8717036

Peter N. Devreotes, Ph.D.

Peter N. Devreotes, Ph.D.

website

Research Topic:  Genetic analysis of chemotaxis in eukaryotic cells

Research

Biological oscillations are universally found in nature and are critical at many levels of cellular organization. In the model organism we study, the social amoeba Dictyostelium discoideum, starvation-triggered cell-cell aggregation and developmental morphogenesis are orchestrated by periodic extracellular cAMP waves, which provide both gradients for chemotactic migration and signals for development. Repeated occupancy of the G protein–coupled cAMP receptors promotes optimal developmental gene expression, whereas continuous stimulation suppresses the program.

Lab Members:
Namesort ascending Classification Email Phone
Zhihua Jiao, Ph.D. Postdoctoral Fellow zjiao3@jhu.edu 410-955-4699
Yu Long Research Specialist yulong@jhmi.edu 410-955-4699
Yu Deng Student ydeng25@jhu.edu 410-955-4699
Yiyan Lin Student ylin123@jhmi.edu 410-955-4699
Xiaoguang Li Student xli82@jhmi.edu 410-955-4699
Wei Qian Research Technologist wqian1@jhmi.edu 410-955-3225
Tatsat Banerjee Student tatsatb@jhu.edu 410-955-4699
Jonathan Kuhn, Ph.D. Postdoctoral Fellow jkuhn14@jhmi.edu 410-955-4699
Jane Borleis Research Specialist jborleis@jhmi.edu 410-955-4699
Huiwang (David) Zhan Postdoctoral Fellow huiwangzhan@jhmi.edu 410-955-4699
Dhiman Pal, Ph.D. Postdoctoral Fellow dpal1@jhmi.edu 410-502-6810
Bedri Sharif Student budri@jhmi.edu 410-955-4699
Research Associates and Staff:
Namesort ascending Position title Email Phone
Randy Huffman Administrator randy@jhu.edu 410-614-4207
Brigitte Walsh Assistant to the Director bwalsh12@jhmi.edu 410-502-6810
Selected Publications:
Jiao Z, Cai H, Long Y, Sirka OK, Padmanaban V, Ewald AJ, Devreotes PN (2020). Statin-induced GGPP depletion blocks macropinocytosis and starves cells with oncogenic defects. Proc Natl Acad Sci U S A, 117(8), 4158-4168. doi: 10.1073/pnas.1917938117.  
Cao Y, Ghabache E, Miao Y, Niman C, Hakozaki H, Reck-Peterson SL, Devreotes PN, and Rappel W-J.  2019. A minimal computational model for three-dimensional cell migration. J. R. Soc. Interface 16:20190619. http://dx.doi.org/10.1098/rsif.2019.0619  
Pal DS*, Li X*, Banerjee T, Miao Y, Devreotes PN. 2019. The Excitable Signal Transduction Networks: Movers and Shapers of Eukaryotic Cell Migration. Int. J. Dev. Biol. 63(8-9-10):407-416. doi: 10.1387/ijdb.190265pd. *Equal contribution.
Li X, Miao Y, Pal DS, Devreotes PN. Excitable networks controlling cell migration during development and disease. Semin Cell Dev Biol. 2019 Dec 10;. doi: 10.1016/j.semcdb.2019.11.001. [Epub ahead of print] Review. PubMed PMID: 31836289; NIHMSID:NIHMS1546309  
Devreotes P (2019). Moving toward molecular mechanisms for chemotaxis in eukaryotic cells. Mol Biol Cell, 30(23), 2873-2877, 2019 Nov 1. doi: 10.1091/mbc.E19-07-0393. PMC6822590.
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.
Miyanaga Y, Kamimura Y, Kuwayama H, Devreotes PN, and Ueda M. (2018). Chemoattractant receptors activate, recruit and capture G proteins for wide range chemotaxis. Biochemical and Biophysical Research Communications. Nov 16. pii: S0006-291X(18)32435-5. doi: 10.1016/j.bbrc.2018.11.029. [Epub ahead of print] PubMed PMID: 30454895.  
Li X, Edwards M, Swaney KF, Singh N, Bhattacharya S, Borleis J, Long Y, Iglesias PA, Chen J, and Devreotes PN. 2018. Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration. PNAS published ahead of print Sept. 7, 2018. https://doi.org/10.1073/pnas.1809039115
Edwards M, Cai H, Abubaker-Sharif  B, Long Y, Lampert T, and Devreotes PN. 2018. Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideumProc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3722-E3730. doi: 10.1073/pnas.1710480115. Epub 2018 Mar 30.
Neumann NM, Perrone MC, Veldhuis JH, Huebner RJ, Zhan H, Devreotes PN, Brodland GW, and Ewald AJ. 2018. Coordination of receptor tyrosine kinase signaling and interfacial tension dynamics drives radial intercalation and tube elongation. Dev Cell Apr 9;45(1):67-82.e6. doi: 10.1016/j.devcel.2018.03.11.  
Artemenko, Y., Devreotes, P. N. Assessment of Dictyostelium discoideum Response to Acute Mechanical Stimulation. J. Vis. Exp.(129), e56411, doi:10.3791/56411 (2017).
Devreotes PN, Bhattacharya S, Edwards M, Iglesias PA, Lampert T, Miao Y. 2017. Excitable Signal Transduction Networks in Directed Cell Migration. Annu Rev Cell Dev Biol Oct. 6;33:103-125. Doi: 10.1146/annurev-cellbio-100616-060739. PMID: 28793794
Lampert TJ, Kamprad N, Edwards M, Borleis J, Watson AJ, Tarantola M, Devreotes PN.  2017. Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity. Proc Natl Acad Sci USA Aug 28. Pii: 201616600. Doi: 10.1073/pnas.1616600114. [Epub ahead of print]. PMCID: PMC5603988
Chen Z, Jiang H, Xu W, Li X, Dempsey DR, Zhang X, Devreotes P, Wolberger C, Amzel M, Gabelli SB, Cole PA.  2017. A Tunable Brake for HECT Ubiquitin Ligases. Molecular Cell 66 (3): 345-357. PMID: 28475870. DOI: 10.1016/j.molcel.2017.03.020
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.
Artemenko Y, Axiotakis L Jr., Borleis J, Iglesias PA, Deveotes PN. 2016. Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks. Proc Natl Acad Sci USA. Nov. 22; 113(47):E7500-E7509. PMCID: PMC5127353 [ link ]
Swaney K.F., Borleis J., Iglesias P.A., and Devreotes, P.N. 2015.  Novel protein Callipygian defines the back of migrating cells. PNAS 2015 Jun 30. pii:201509098. [Epub ahead of print]
Tang M, Wang M, Shi C, Iglesias PA, Devreotes PN, and Huang CH  (2014).  Evolutionarily conserved coupling of adaptive and excitable networks mediates eukaryotic chemotaxis. Nat Commun. Oct 27;5:5175. PMCID: PMC4211273 [Available on 2015/4/27)]
Cai H, Katoh-Kurasawa M, Muramoto T, Santhanam B, Long Y, Li L, Ueda M, Iglesias PA, Shaulsky G, and Devreotes PN. Nucleocytoplasmic shuttling of a GATA transcription factor functions as a development timer. Science. 2014 Mar 21;343(6177):1249531. doi: 10.1126/science.1249531.
Huang, C.,Tang, M., Shi, C., Iglesias, P., and Devreotes, P.N. An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat Cell Biol. 2013 Nov;15(11):1307-16.
Shi, C., Huang, C., Devreotes, P.N., and Iglesias, P.  2013. Interaction of motility, directional sensing, and polarity modules recreates the behaviors of chemotaxing cells. PLOS Computational Biol. 2013 Jul;9(7):e1003122. 
Cai, H., Das, S., Kamimura, Y., Comer, F.I., Parent, D.A., and Devreotes, P.N.  2010  Ras-mediated activation and inactivation of the TorC2-PKB pathway are critical for chemotaxis.  J. Cell Biol., 190:233-245. PMCID: PMC2930282
Swaney, K.F., Huang, C.H., Devreotes, P.N. 2010. Eukaryotic Chemotaxis: A network of signaling pathways controls motility, directional sensing, and polarity. Annu Rev Biophys 278:20445-20448.
Xiong, Y., Huang, C-H, Iglesias, P.A., and Devreotes, P.N. 2010. Cells navigate with a local-excitation, global-inhibition-biased excitable network. PNAS, 107:17079-17086.
Janetopoulos C, Ma L, Devreotes PN, Iglesias PA. Chemoattractant-induced phosphatidylinositol 3,4,5-trisphosphate accumulation is spatially amplified and adapts, independent of the actin cytoskeleton. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8951-6. PMC428453
Iijima, M. and Devreotes, P. N. 2002. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599-610 (Cover).
Janetopoulos, C., Jin, T. and Devreotes, P.N. 2001. Receptor mediated activation of heterotrimeric G-proteins in living cells. Science, 291, 2408-2411.
Parent, C. and Devreotes, P.N. 1999. A Cell's Sense of Direction. Science, 284, 765-770.
Parent, C., Blacklock, B., Froelich, W., Murphy, D. and Devreotes, P.N. 1998. G protein signaling events are activated at the leading edge of chemotactic cells. Cell, 95, 81-91.
Chen MY, Long Y, Devreotes PN. A novel cytosolic regulator, Pianissimo, is required for chemoattractant receptor and G protein-mediated activation of the 12 transmembrane domain adenylyl cyclase in Dictyostelium. Genes Dev. 1997 Dec 1;11(23):3218-31. PMC316743
Xiao Z, Zhang N, Murphy DB, Devreotes PN. Dynamic distribution of chemoattractant receptors in living cells during chemotaxis and persistent stimulation. J Cell Biol. 1997 Oct 20;139(2):365-74. PMC2139806
Insall R, Kuspa A, Lilly PJ, Shaulsky G, Levin LR, Loomis WF, Devreotes P. CRAC, a cytosolic protein containing a pleckstrin homology domain, is required for receptor and G protein-mediated activation of adenylyl cyclase in Dictyostelium. J Cell Biol. 1994 Sep;126(6):1537-45. PMC2290948
Lilly P, Wu L, Welker DL, Devreotes PN. A G-protein beta-subunit is essential for Dictyostelium development. Genes Dev. 1993 Jun;7(6):986-95. PMID: 8099335.
Pitt, G.S., Milona, N., Borleis, J., Lin, K.C., Reed, R.R. and Devreotes, P.N. 1992. Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyosteilum development. Cell 69, 305-315.
Klein, P.S., Sun, T.L., Saxe, C.L. III, Kimmel, A.R., Johnson, R.L. and Devreotes, P.N.  1988.  A chemoattractant receptor controls development in Dictyostelium discoideum. Science 241, 1467-1472.
Tomchik KJ, Devreotes PN. Adenosine 3',5'-monophosphate waves in Dictyostelium discoideum: a demonstration by isotope dilution--fluorography. Science. 1981 Apr 24;212(4493):443-6. (Cover Article). PMID: 6259734
Devreotes PN, Steck TL. Cyclic 3',5' AMP relay in Dictyostelium discoideum. II. Requirements for the initiation and termination of the response. J Cell Biol. 1979 Feb;80(2):300-9. PMC2110342

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