Miho Iijima, Ph.D.

Environmental Sensing and Signal Transduction

Cells sense and respond to their environments with remarkable precision, enabling them to control behavior, metabolism, and fate in multicellular organisms. The Iijima Laboratory studies how cells detect extracellular cues, such as chemoattractants, hormones, and growth factors, as well as intracellular environments, including metabolic imbalance, organelle stress, and DNA damage. We focus on how these external and internal signals are integrated through shared signaling networks to guide cellular responses in health and disease.

Our research centers on intracellular signal transduction pathways downstream of G protein-coupled receptors and receptor tyrosine kinases, with particular emphasis on PI3-kinase, PTEN, mTORC2, AKT, and small GTPases of the Ras and Rho families. These pathways regulate diverse processes, including chemotactic migration, glucose homeostasis, cell proliferation, DNA repair, bioenergetics, and brain development. We also study innate immune signaling, focusing on how aberrant DNA species generated by mitochondrial dysfunction or genomic stress activate DNA-sensing pathways, including STING-mediated signaling, and how these responses intersect with metabolic and growth control pathways to determine adaptive versus pathological outcomes.

To achieve these goals, our laboratory combines state-of-the-art cell biological approaches, including protein biochemistry, deep mutational analysis, genome-editing technologies, live-cell and advanced microscopy, and mouse models. Through these integrated approaches, we aim to uncover fundamental principles of cellular signaling and translate them toward therapeutic strategies for diseases such as cancer, diabetes, and inflammatory disorders.

Complete List of Publications

https://www.ncbi.nlm.nih.gov/myncbi/miho.iijima.1/bibliography/public/

Selected Publications

Iwata W, Adachi Y, West JJ, Ewald AJ, Zheng Y, Wood LD, Anders RA, Sesaki H, Iijima M. (2025). Context-dependent inhibitory roles of RhoA in 3D invasive cell migration within the extracellular matrix. Cell Rep. 44: 116649

Iwata W, Haggerty N, Sesaki H, Iijima M. (2025). Targeting mitochondrial structure and dynamics for therapeutic intervention in cancer. PLoS Biol. 23: e3003453.

Ito F, Iwata W, Adachi Y, Sesaki H, Iijima M. (2025). GRHL2-HER3 and E-cadherin mediate EGFR-bypass drug resistance in lung cancer cells. Front Cell Dev Biol. 12: 1511190

Yamada T, Ikeda A, Murata D, Wang H, Zhang C, Khare P, Adachi Y, Ito F, Quirós PM, Blackshaw S, López-Otín C, Langer T, Chan DC, Le A, Dawson VL, Dawson TM, Iijima M*, Sesaki H*. (2025). Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1. Nature. 639: 776-78. *Co-corresponding authors

Murata D, Ito F, Tang G, Iwata W, Yeung N, West JJ, Ewald AJ, Wang X, Iijima M*, Sesaki H*. (2024). mCAUSE: Prioritizing mitochondrial targets that alleviate pancreatic cancer cell phenotypes. iScience. 27: 110880. *Co-corresponding authors.

Kato T, Igarashi A, Sesaki H, Iijima M. (2021). Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation. Genes Cells. 26: 1014-1022

Senoo H, Murata D, Wai M, Arai K, Iwata W, Sesaki H, Iijima M. (2021). KARATE: Protein kinase A-induced KRAS4B-RHOA-mTORC2 supercomplex that phosphorylates AKT in insulin signaling. Mol Cell. 81: 4622-4634

Kato T, Murata D, Anders RA, Sesaki H, Iijima M. (2021). Nuclear PTEN and p53 suppress stress-induced liver cancer through distinct mechanisms. Biochem Biophys Res Commun. 549: 83-90

Igarashi A, Kato T, Sesaki H, Iijima M. (2021). Nuclear PTEN deficiency and heterozygous PTEN loss have distinct impacts on brain and lymph node size. Biochem Biophys Res Commun. 555: 81-88.

Senoo H, Wai M, Matsubayashi HT, Sesaki H, Iijima M. (2020). Hetero-oligomerization of Rho and Ras GTPases Connects GPCR Activation to mTORC2-AKT Signaling. Cell Rep. 33: 108427

Senoo H, Kamimura K, Kimura R, Nakajima A, Sawai S, Sesaki H, Iijima M. (2019). Phosphorylated Rho-GDP directly activates mTORC2 Kinase toward AKT through dimerization with Ras-GTP to regulate cell migration. Nat. Cell Biol. 21: 867-878.

Kriebel PW, Majumdar R, Jenkins LM, Senoo H, Wang W, Ammu S, Chen S, Narayan K, Iijima M, Parent CA. (2018). Extracellular vesicles direct migration by synthesizing and releasing chemotactic signals. J Cell Biol. 217: 2891-2910.

Igarashi A, Itoh K, Yamada T, Adachi Y, Kato T, Murata D, Sesaki H, Iijima M. (2018). Nuclear PTEN deficiency causes microcephaly with decreased neuronal soma size and increased seizure susceptibility. J Biol Chem. 293: 9292-9300

Yang JM, Schiapparelli P, Nguyen HN, Igarashi A, Zhang Q, Abbadi S, Amzel LM, Sesaki H, Quiñones-Hinojosa A, Iijima M. (2017). Characterization of PTEN mutations in brain cancer reveals that PTEN mono-ubiquitination promotes protein stability and nuclear localization. Oncogene. 36: 3673-3685

Senoo H, Cai H, Wang Y, Sesaki H, and Iijima M. The novel racE binding protein GflB sharpens ras activity at the leading edge of migrating cells. (2016). Mol Biol Cell. 27:1596-1605.

 Nguyen H-N, Yang J-M, Rahdar M, Keniry M, Swaney KF, Parsons R, Park BH, Sesaki H, Devreotes PN, Iijima M. (2015). A new class of cancer-associated PTEN mutations defined by membrane translocation defects. Oncogene. 34:3737-43.

Nguyen H-N, Yang J-M, Miyamoto T, Itoh K, Rho E, Zhang Q, Inoue T, Devreotes PN, Sesaki H, Iijima M. (2015). Opening the conformation is a master switch for the dual localization and phosphatase activity of PTEN. Sci Rep. 5:12600.

Nguyen H-N, Yang J-M, Afkari Y, Park BH, Sesaki H, Devreotes PN, Iijima M. (2014). Engineering ePTEN: an enhanced PTEN with increased tumor suppressor activities. Proc Natl Acad Sci USA. 2014;111: E2684-2693.

Nguyen H-N, Afkari Y, Senoo H, Sesaki H, Devreotes PN, Iijima M. (2014). Mechanism of human PTEN localization revealed by heterologous expression in Dictyostelium. Oncogene. 33: 5688-5696.

Wang Y, Senoo H, Sesaki H, Iijima M. (2013). Rho GTPases orient gradient sensing in chemotaxis. Proc Natl Acad Sci USA. 110: E4723-4732.

Wang Y, Steimle PA, Ren Y, Ross CA, Robinson DN, Egelhoff TT, Sesaki H, Iijima M. (2011). Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation. Mol Biol Cell. 22: 2270-2281

Chen C-L, Wang Y, Sesaki H, Iijima M. (2012). Myosin I links PIP₃ signaling to remodeling of the actin cytoskeleton in chemotaxis. Science Signaling. 5: ra10

Iijima M, Huang YE, Luo HR, Vazquez F, Devreotes PN. Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis. (2004). J Biol Chem. 16: 16606-16613 (Selected by Faculty of 1000).

Luo HR, Huang YE, Chen JC, Saiardi A, Iijima M, Ye K, Huang Y, Nagata E, Devreotes PN, Snyder SH. (2003). Inositol Pyrophosphates Mediate Chemotaxis in Dictyostelium via Pleckstrin Homology Domain-PtdIns(3,4,5)P3 Interactions. Cell. 114: 559-572 (Selected by Faculty of 1000).

 Iijima M, Devreotes PN. (2002). Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell. 109:599-610 (Cover page picture) (Selected by Faculty of 1000).

Biosketch