Fighting against COVID-19

COVID-19 is now a worldwide pandemic; more than 5.2M have contracted the coronavirus with 5-8% fatality. The United States has over 2.0M cases, with more than 115,000 deaths as of June 2020. The highly efficient transmission ability of SARS-CoV-2 without apparent symptoms can be one of the pandemic's central causes. It is an urgent mission to intercept SARS-CoV-2 transmission from multiple aspects, including identifying genetic vulnerability, environmental health, and vaccinations. Our devastating situation in NY impels us to strive against the deadly virus.

RESEARCH

FUNCTIONAL STEM CELLS

Dr. Mori has developed a powerful tool for the identification and characterization of "functional" pluripotent stem cells (PSCs) in our model system of lung generation. A significant advantage of this development is the improved organ formation ability of PSCs, which allows the most efficient respiratory organ formation in vivo.

LUNG GENERATION via

ADVANCED DEVELOPMENTAL ENGINEERING

Our understanding of complex organ bioengineering is minimal. Unlocking the mysteries behind sophisticated organ formation, we will gain the power for controlling bioengineered respiratory organ in our model system, and for developing tools to further explore this research avenue with more sensitive measurements and improved data collection.

CONDITIONAL BLASTOCYST COMPLEMENTATION

for generating "functional" lungs in vivo

In an effort to gain a better understanding of respiratory organ generation, we have recently developed a state-of-the-art methodology, conditional blastocyst complementation. This allows us to focus on predominantly investigating the formation of the lungs in our experimental model. We are currently looking to expand this technology for patients suffering from refractory lung diseases.

SELECTED PUBLICATIONS

Shimamura Y*, Tanaka J*, Miura A, Kakiuchi M, Sarmah H, Miura A, Hwang Y, Sawada A, Ninish Z, Yamada K, Cai J*, Mori M†* A developmental program that regulates mammalian organ size offsets evolutionary distance, bioRxiv 2022.10.19.512107; doi: https://doi.org/10.1101/2022.10.19.512107

https://www.biorxiv.org/content/10.1101/2022.10.19.512107v1

†Corresponding author, *, *equally contributed

Miura A, Sarmah H, Tanaka J, Hwang Y, Sawada A, Shimamura Y, Fang Y, Shimizu D, Ninish Z, Suer JL, Dubois N, Davis J, Toyooka S, Wu J, Que J, Hawkins FJ, Lin SH, Mori M† Conditional blastocyst complementation of a defective Foxa2 lineage efficiently promotes generation of the whole lung,

bioRxiv 2022.10.31.514628, doi: https://doi.org/10.1101/2022.10.31.514628

https://www.biorxiv.org/content/10.1101/2022.10.31.514628v2

†Corresponding author

Sarmah H, Sawada A, Hwang Y, Miura A, Shimamura Y, Tanaka J, Yamada K, Mori M†

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy. Front. Cell Dev. Biol. 2023, 11:1070560. doi: 10.3389/fcell.2023.1070560, 2023., †Corresponding author

Tanaka J*, Senpuku H, Ogawa M, Yasuhara R, Ohnuma S, Takamatsu K, Watanabe T, Mabuchi Y, Nakamura Y, Ishida S, Sadaoka T, Takaki T, Shirota T, Shimane T, Inoue T, Sakai T, Mori M, Tsuji T, Saito I, and Mishima K. Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication, Nat Cell Biol., Oct (17) 2022, doi.org/10.1038/s41556-022-01007-6

Serra CFH, Liu H, Qian J, Mori M, Lu J, Cardoso WV. Prominin 1 and Notch regulate ciliary length and dynamics in multiciliated cells of the airway epithelium. iScience. 2022 Jul 14;25(8):104751. PMID: 35942101

Gwon K, Park JD, Lee S, Choi WI, Hwang Y, Mori M, Yu JS, Lee DN. Injectable hyaluronic acid hydrogel encapsulated with Si-based NiO nanoflower by visible light cross-linking: Its antibacterial applications, Int J Biol Macromol. 2022 May 31;208:149-158. PMID: 35304194.

Hazan R, Mori M, Danielian PS, Guen VJ, Rubin SM, Cardoso WV, Lees JAE2F4's cytoplasmic role in multiciliogenesis is mediated via an N-terminal domain that binds two components of the centriole replication machinery, Deup1 and SAS6. Mol Biol Cell. 2021 Oct 1;32(20):ar1. doi: 10.1091/mbc.E21-01-0039. Epub 2021 Jul 14.PMID: 34260288.

Stupnikov MR, Yang Y, Mori M, Lu J, Cardoso WV. Jagged and Delta-like ligands control distinct events during airway progenitor cell differentiation. Elife. 2019 Oct 21;8. pii: e50487. doi: 10.7554/eLife.50487.

Mori M†, Furuhashi K, Danielsson AJ, Hirata Y, Yamamoto M, Lin SC, Ohta M, Riccio P, Takahashi Y, Xu X, Emala WC, Lu C, Nakauchi H†, Cardoso VW†. Generation of functional lungs via conditional blastocyst complementation using pluripotent stem cells. Nature Medicine. 2019, in press. †: corresponding author

Yang Y, Riccio P, Schotsaert M, Mori M, Lu J, Lee DK, García-Sastre A, Xu J, Cardoso WV. Spatial-Temporal Lineage Restrictions of Embryonic p63+ Progenitors Establish Distinct Stem Cell Pools in Adult Airways. Dev Cell. 2018 Mar 26;44(6):752-761.e4. PMID: 29587145

Hou Z, Wu Q, Sun X, Chen H, Li Y, Zhang Y, Mori M, Yang Y, Que J, Jiang M. Wnt/Fgf crosstalk is required for the specification of basal cells in the mouse trachea. Development. 2019 Feb 11;146(3). PMID: 30696710

Zhang Y, Yang Y, Jiang M, Huang SX, Zhang W, Al Alam D, Danopoulos S, Mori M, Chen YW, Balasubramanian R, Chuva de Sousa Lopes SM, Serra C, Bialecka M, Kim E, Lin S, Toste de Carvalho ALR, Riccio PN, Cardoso WV, Zhang X, Snoeck HW, Que J. 3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling. Cell Stem Cell. 2018 Sep 13. PMID: 30244870

Mori M, Hazan R, Danielian PS, Mahoney JE, Li H, Lu J, Miller ES, Zhu X, Lees JA, Cardoso WV. Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis. Nature Commun. 2017 Jul 4;8:15857. PMID:28675157

Tsao PN, Matsuoka C, Wei SC, Sato A, Sato S, Hasegawa K, Chen HK, Ling TY, Mori M, Cardoso WV, Morimoto M. Epithelial Notch signaling regulates lung alveolar morphogenesis and airway epithelial integrity. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8242-7. Epub 2016 Jun 30. PMID:27364009

Mori M, Mahoney JE, Stupnikov MR, Paez-Cortez JR, Szymaniak AD, Varelas X, Herrick DB, Schwob J, Zhang H, Cardoso WV.Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors. Development. 2015 Jan 15;142(2):258-67. PMID:25564622

Kurmann AA, Serra M, Hawkins F, Rankin SA, Mori M, Astapova I, Ullas S, Lin S, Bilodeau M, Rossant J, Jean JC, Ikonomou L, Deterding RR, Shannon JM, Zorn AM, Hollenberg AN, Kotton DN. Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells. Cell Stem Cell. 2015 Nov 5;17(5):527-42. Epub 2015 Oct 22. PMID:26593959

Murata Y, Kotani T, Supriatna Y, Kitamura Y, Imada S, Kawahara K, Nishio M, Daniwijaya EW, Sadakata H, Kusakari S, Mori M, Kanazawa Y, Saito Y, Okawa K, Takeda-Morishita M, Okazawa H, Ohnishi H, Azuma T, Suzuki A, Matozaki T. Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):E4264-71. PMID:26195794

Mori M, and Cardoso WV. Lung Progenitor Cell Specification and Morphogenesis. Ed.: R. Harding, K. E. Pinkerton, The Lung: Development, Aging and the Environment, Elsevier Science, Oct 2014.

Mahoney JE, Mori M, Szymaniak AD, Varelas X, Cardoso WV. The hippo pathway effector Yap controls patterning and differentiation of airway epithelial progenitors. Dev Cell. 2014 Jul 28;30(2):137-50. Epub 2014 Jul 17. PMID:25043473

Mantilidewi KI, Murata Y, Mori M, Otsubo C, Kotani T, Kusakari S, Ohnishi H, Matozaki T. Shear stress-induced redistribution of vascular endothelial-protein-tyrosine phosphatase (VE-PTP) in endothelial cells and its role in cell elongation. J Biol Chem. 2014 Mar 7;289(10):6451-61. Epub 2014 Jan 22. PMID:24451369

Mori M, Murata Y, Kotani T, Kusakari S, Ohnishi H, Saito Y, Okazawa H, Ishizuka T, Mori M, Matozaki T. Promotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrins. J Cell Physiol. 2010 Jul;224(1):195-204. PMID:20301196

Murata Y, Mori M, Kotani T, Supriana Y, Okazawa H, Kusakari S, Saito Y, Ohnishi H and Matozaki T. Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatase and their complex formations with Grb2 or Fyn. Genes. Cells. 15: 513-524, 2010 PMID: 20398064

Matozaki T, Murata Y, Mori M, Kotani T, Okazawa H, Ohnishi H. Expression, localization, and biological function of the R3 subtype of receptor-type protein tyrosine phosphatases in mammals. Cell Signal. 2010 Dec;22(12):1811-7. Epub 2010 Jul 12. Review. PMID:20633639