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DDS | Kyushu University, Japan, 2000
PhD | Kyushu University, Japan, 2004
The aim of our laboratory is to understand the cellular and molecular mechanisms in craniofacial birth defects and diseases such as cleft lip and palate, tooth developmental defects, bone diseases, muscle disorders, and Sjögren’s syndrome. Specifically, we are working to characterize the cell-signaling network and cellular metabolic processes related to membrane trafficking, using multidisciplinary approaches—including genetics, genomics, proteomics, bioinformatics, biochemistry, and molecular biology. The following research projects are ongoing in our laboratory:
Cellular metabolic aberrations (including abnormal cholesterol metabolism) result in craniofacial deformities in humans and mice. Interestingly, mice with cholesterol synthesis deficiency have severe malformations specifically in the craniofacial region. Because the majority of cells in the craniofacial region stem from cranial neural crest (CNC) cells—which is a multi-potent cell population that gives rise to a variety of different cell types—we conclude that CNC cells are more sensitive to cellular metabolic aberrations than are cells from other regions during embryogenesis. However, the mechanism behind how molecules related to cellular metabolism are regulated during craniofacial development is still unknown. In addition, the possible relationship between cellular metabolism and craniofacial deformities remain unclear. The aim of our laboratory is to identify gene mutations and protein modifications related to craniofacial disorders and provide the basis for tests aimed at identifying higher-risk persons.
Autophagy is an evolutionarily conserved bulk-protein degradation system, in which isolation membranes engulf cytoplasmic constituents and the resulting autophagosomes transport them to lysosomes. This process is critical for the removal and breakdown of cellular components such as damaged proteins and aged organelles. Because autophagic activity is altered in various diseases and birth defects in humans and mice, an understanding of the way autophagy is regulated is critical for understanding both normal craniofacial development and congenital malformations. The aim of our laboratory is to identify the molecular regulatory mechanism of autophagic machinery related to developmental defects and diseases.
Craniofacial skeletal defects are one of the most prominent genetic disorders. However, the etiology of these defects remains largely unclear. This study will provide a new insight into cholesterol metabolism in craniofacial skeletal development, and will have a significant impact on the therapeutics of various types of bone diseases.
Various mutations in genes and proteins involved in signal transduction cause muscle abnormalities in both humans and mice. This study will provide insights into muscular disorders caused by mutations in genes involved in WNT/β-catenin signaling pathway. The results of this work will facilitate an understanding of how altered WNT/β-catenin signaling results in defects in muscle development and regeneration.
The etiology of cleft lip with/without cleft palate is complicated with a variety of genetic and environmental factors. This study will identify the distribution and contribution of non-coding RNAs (ncRNAs) in lip and palate development. The results of this study will facilitate our understanding of the role of ncRNAs in lip and palate development and will enable us to design future therapeutic approaches to diagnose and prevent cleft lip with/without cleft palate.
1. Xu H, Yan F, Hu R, Suzuki A, Iwaya C, Jia P, Iwata J#, and Zhao Z# (2021) CleftGeneDB: A resource for annotating genes associated with cleft lip and cleft palate. Science Bulletin. #: Corresponding authors.
2. Yoshioka H, Mikami Y, Ramakrishnan SS, Suzuki A, and Iwata J (2021) MicroRNA-124-3p plays a crucial role in cleft palate induced by retinoic acid. Frontiers in Cell and Developmental Biology. 2021 Jun 9;9:621045. PMID: 34178974.
3. Yoshioka H, Li A, Suzuki A, Ramakrishnan SS, Zhao Z, and Iwata J (2021) Identification of microRNAs and gene regulatory networks in cleft lip common in humans and mice. Human Molecular Genetics. 2021 Jun 8:ddab151. PMID: 34104955.
4. Yoshioka H, Wang Y, Suzuki A, Shayegh M, Gajera M, Zhao Z, and Iwata J (2021) Overexpression of miR-1306-5p, miR-3195, and miR-3914 inhibits ameloblast differentiation through suppression of genes associated with human amelogenesis imperfecta. International Journal of Molecular Sciences. 2021 Feb 23;22(4):2202. PMID: 33672174.
5. Yoshioka H, Ramakrishnan SS, Suzuki A, and Iwata J (2021) Phenytoin inhibits cell proliferation through microRNA-196a-5p in mouse lip mesenchymal cells. International Journal of Molecular Sciences. 2021 Feb 9;22(4):1746. PMID: 33572377.
6. Yoshioka H, Ramakrishnan SS, Shim J, Suzuki A, and Iwata J (2021) Excessive all-trans retinoic acid inhibits cell proliferation through upregulated microRNA-4680-3p in cultured human palate cells. Frontiers in Cell and Developmental Biology. 2021 Jan 28;9:618876. PMID: 33585479.
7. Yan F, Jia P, Suzuki A, Iwata J#, and Zhao Z# (2020) A developmental stage specific network approach for studying dynamic transcription factor-microRNA co-regulation during craniofacial
development. Development. 2020 Dec 24;147(24):dev192948. PMID: 33234712. #: Corresponding authors.
8. Yang Y, Suzuki A, Iwata J, and Jun G (2020) Secondary Genome-Wide Association Study using novel analytical strategies disentangle genetic components of cleft lip and/or cleft palate in 1q32.2. Genes. 2020 Oct 29;11(11):1280. PMID: 33137956.
9. Suzuki A, Ogata K, Yoshioka H, Shim J, Wassif CA, Porter FD, and Iwata J (2020) Cholesterol metabolism regulates bone formation and homeostasis through primary cilium formation. Bone Research. Jan 2;8:1. PMID: 31934493.
10. Suzuki A, Summakia D, Desai NG, Jun G, Jia P, Gajera MV, Zhao Z, and Iwata J (2019) MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse. BMC Genomics.Nov 14;20(1):852. PMID: 31727022.
11. Suzuki A, Shim J, Ogata K, Yoshioka H, and Iwata J (2019) Cholesterol metabolism plays a crucial role in the regulation of autophagy for cell differentiation of granular convoluted tubules in male mouse submandibular glands. Development. Oct 17;146(20). PMID: 31558435.
12. Li A, Jia P, Malik S, Fei R, Yoshioka H, Suzuki A, Iwata J, and Zhao Z (2019) Critical microRNAs and regulatory motifs in cleft palate identified by a conserved microRNA-TF-gene network approach in humans and mice. Briefings in Bioinformatics. Oct 7, PMID: 31589286.
13. Gajera M, Desai N, Suzuki A, Li A, Zhang M, Jun G, Jia P, Zhao Z, and Iwata J (2019) MicroRNA-655-3p and microRNA-497-5p inhibit cell proliferation in cultured human lip cells through the regulation of genes related to human cleft lip. BMC Medical Genomics. May 23;12(1):70. PMID: 31122291.
14. Suzuki A, Li A, Gajera M, Abdallah N, Zhang M, Zhao Z, and Iwata J (2019) MicroRNA-374a, -4680, and -133b suppress cell proliferation through the regulation of genes associated with human cleft palate in cultured human palate cells. BMC Medical Genomics. Jul 1;12(1):93. PMID: 31262291.
15. Yan F, Dai Y, Iwata J, Zhao Z, and Jia P (2020) An integrative, genomic, transcriptomic and network-assisted study to identify genes associated with human cleft lip with or without cleft palate. BMC Medical Genomics. 13(Suppl 5):39, PMID: 32241273.
16. Li A, Qin G, Suzuki A, Gajera M, Iwata J, Jia P, and Zhao Z (2019) Network-based identification of critical regulators as putative drivers of human cleft lip. BMC Medical Genomics. 2019, Jan 31;12(Suppl 1):16. PMID: 30704473.
17. Suzuki A, Minamide R, and Iwata J (2018) The role of acetyltransferases for the temporal-specific accessibility of β-catenin to the myogenic gene locus. Scientific Reports. Oct 10;8(1):15057. PMID: 30305648.
18. Suzuki A, Minamide R, and Iwata J (2018) WNT/β-catenin signaling plays a crucial role in myoblast fusion through the regulation of Nephrin expression during development. Development. Nov 27;145(23). PMID: 30389854.
19. Suzuki A, Jun G, Abdallah N, Gajera M, and Iwata J (2018) Gene datasets associated with mouse cleft palate. Data in Brief. Mar 14;18:655-673. PMID: 29896534.
20. Suzuki A, Abdallah N, Gajera M, Jun G, Jia P, Zhao Z, and Iwata J (2018) Genes and microRNAs associated with mouse cleft palate: a systematic review and bioinformatics analysis. Mechanisms of Development. Apr;150:21-27. PMID: 29475039.
21. Carlock C, Wu J, Shim J, Moreno-Gonzalez I, Pitcher MR, Hicks J, Suzuki A, Iwata J, Quevado J, and Lou Y (2017) Interleukin33 deficiency causes tau abnormality and neurodegeneration with Alzheimer-like symptoms in aged mice. Transl. Psychiatry. Jul 4;7(7):e1164. PMID: 28675392.
22. Suzuki A, Pelikan RC, and Iwata J (2015) WNT/β-catenin signaling regulates multiple steps of myogenesis by regulating step-specific targets. Mol. Cell. Biol. May 15; 35 (10): 1763-76. PMID: 25755281.
23. Ho TV*, Iwata J*, Ho HA, Grimes WC, Park S, Sanchez-Lara PA, and Chai Y (2015) Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development. Dev. Biol. Apr 15; 400 (2): 180-90. (*These authors contributed equally to this work.)
24. Iwata J, Suzuki A, Yokota T, Ho TV, Pelikan RC, Urata M, Sanchez-Lara P, and Chai Y (2014) TGFβ regulates epithelial–mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate. Development, Feb; 141 (4): 909-17.
25. Iwata J, Suzuki A, Pelikan RC, Ho TV, Sanchez-Lara PA, and Chai Y (2014) Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice. Hum. Mol. Genetics, Jan 1; 23 (1): 182-93.
26. Iwata J, Suzuki A, Pelikan RC, Ho TV, and Chai Y (2013) Cranial neural crest cells regulate tongue muscle formation via TGFβ–mediated BMP and FGF signaling. J. Biol. Chem. 288: 29760-70.
27. Parada C, Li J, Iwata J, Suzuki A, and Chai Y (2013) CTGF mediates Smad-dependent transforming growth factor β signaling to regulate mesenchymal cell proliferation during palate development. Mol. Cell Biol., Sep; 33 (17): 3482-93.
28. Koike M, Tanida I, Nanao T, Tada N, Iwata J, Ueno T, Kominami E, and Uchiyama Y (2013) Enrichment of GABARAP relative to LC3 in the axonal initial segments of neurons. PLoS ONE, May 9; 8 (5): e63568.
29. Song ZC*, Liu C*, Iwata J*, Gu SP, Suzuki A, Sun C, He W, Shu R, Li L, Chai Y, and Chen YP (2013) Mice with Tak1-deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development. J. Biol. Chem., Apr 12; 288 (15): 10440-50. *These authors contributed equally to this work.
30. Iwata J, Suzuki A, Pelikan RC, Ho TV, Sanchez-Lara PA, Urata M, Dixon MJ, and Chai Y (2013) Smad4–Irf6 genetic interaction and TGFβ–mediated IRF6 signaling cascade are crucial for palatal fusion in mice. Development, Mar; 140 (6): 1220-30.
31. Pelikan RC*, Iwata J*, Suzuki A, Chai Y, and Hacia JG (2013) Identification of candidate downstream targets of TGFβ signaling during palate development by genome-wide transcript profiling. J. Cell Biochem., Apr, 114: 796-807. *These two authors contributed equally to this work.
32. Iwata J, Hacia JG, Suzuki A, Sanchez-Lara PA, Urata M, and Chai Y (2012) Modulation of non-canonical TGF-β signaling prevents cleft palate in Tgfbr2 mutant mice. J. Clin. Invest., Mar 1; 122 (3): 873-85.
33. Iwata J, Tung L, Urata M, Hacia JG, Suzuki A, Ramenzoni L, Chaudhry O, Parada C, Sanchez-Lara PA, and Chai Y (2012) Fibroblast growth factor 9 (FGF9)–pituitary homeobox 2 (PITX2) pathway mediates transforming growth factor beta (TGFβ) signaling to regulate cell proliferation in palatal mesenchyme during mouse palatogenesis. J. Biol. Chem., Jan 20; 287 (4): 2353-63.
34. Okamoto K, Okamoto Y, Kawakubo T, Iwata J, Yasuda Y, Tsukuba T, and Yamamoto K (2011) Role of the transcription factor Sp1 in regulating the expression of the murine cathepsin E gene. J. Biochem., Nov 30; 151 (3): 263-72.
35. Hochheiser H, Aronow BJ, Artinger K, Beaty TH, Brinkley JF, Chai Y, Clouthier D, Cunningham ML, Dixon M, Donahue LR, Fraser SE, Iwata J, Marazita ML, Murray JC, Murray S, Postlethwait J, Potter S, Shapiro L, Spritz R, Visel A, Weinberg SM, Trainor PA (2011) The FaceBase Consortium: A comprehensive program to facilitate craniofacial research. Dev. Biol., Jul 15; 355 (2): 175-182.
36. Huang XF, Yokota T, Iwata J, Chai Y (2011) TGF-β mediated FasL–Fas–Caspase pathway is crucial during palatogenesis. Journal of Dental Research, Aug; 90 (8): 981-987.
37. Ezaki J, Matsumoto N, Takeda-Ezaki M, Komatsu M, Takahashi K, Hiraoka Y, Taka H, Fujimura T, Takehana K, Yoshida M, Iwata J, Tanida I, Furuya N, Zheng D, Tada N, Tanaka K, Kominami E, and Ueno T (2011) Liver autophagy contributes to the maintenance of blood glucose and amino acid levels. Autophagy, Jul; 7 (7): 727-736.
38. Chung IH, Han J, Iwata J, and Chai Y (2010) Msx1 and Dlx5 function synergistically to regulate frontal bone development. Genesis, Vol. 48 (11) 645-655.
39. Iwata J, Hosokawa R, Sanchez-Lara PA, Urata M, Slavkin H, and Chai Y (2010) Transforming growth factor-beta regulates basal transcriptional regulatory machinery to control cell proliferation and differentiation in cranial neural crest–derived osteoprogenitor cells. J. Biol. Chem., Feb 12; 285 (7): 4975-82.
40. Hosokawa R, Oka K, Yamaza T, Iwata J, Urata M, Xu X, Bringas P Jr, Nonaka K, and Chai Y (2010) TGF-β mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue–tissue interactions during tongue morphogenesis. Dev. Biol., 341 (1): 186-95.
41. Sou Y*, Waguri S*, Iwata J*, Ueno T, Fujimura T, Hara T, Sawada N, Yamada A, Mizushima N, Uchiyama Y, Kominami E, Tanaka K, Komatsu M (2008). The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol. Biol. Cell, 19 (11); 4762-75. *These three authors contributed equally to this work.
42. Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, and Tanaka K (2007). Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell, 131, 1149-1163.
43. Kawakubo T, Okamoto K, Iwata J, Shin M, Okamoto Y, Yasukochi A, Nakayama K, Kadowaki T, Tsukuba T, and Yamamoto K (2007). Cathepsin E prevents tumor growth and metastasis by catalyzing the proteolytic release of soluble TRAIL from tumor cell surface. Cancer Research, 67 (22): 10869-78.
44. Shin M, Kadowaki T, Iwata J, Kawakubo T, Yamaguchi N, Takii R, Tsukuba T, and Yamamoto K (2007). Association of cathepsin E with tumor growth arrest through angiogenesis inhibition and enhanced immune responses. Biol. Chem., 388 (11): 1173-81.
45. Komatsu M, Wang QJ, Holstein GR, Friedrich VL Jr, Iwata J, Kominami E, Chait BT, Tanaka K, and Yue Z (2007). Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration. Proc. Natl. Acad. Sci. USA, Sep 4; 104 (36): 14489-94.
46. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, and Tanaka K (2006). Loss of autophagy in the central nervous system causes neurodegeneration. Nature, 441 (7095), 880-884.
47. Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I, Chiba T, Tanaka K, and Kominami E (2006) Excess peroxisomes are degraded by autophagic machinery in mammals. J. Biol. Chem., 281, 4035-41.
48. Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, and Chiba T (2005) Impairment of starvation–induced and constitutive autophagy in Atg7–deficient mice. J. Cell Biol., 169, 425-434.
1. Suzuki A and Iwata J (2021) Amino acid metabolism and autophagy in skeletal development and homeostasis. Bone. 2021 May;146:115881. PMID: 33578033.
2. Suzuki A, Ogata K, and Iwata J (2021) Cell signaling regulation in salivary gland development. Cellular and Molecular Life Sciences. 2021 Jan 15. PMID: 33449148.
3. Suzuki A, Minamide M, Iwaya C, Ogata K, and Iwata J (2020) Role of metabolism in bone development and homeostasis. International Journal of Molecular Sciences. 2020 Nov 26;21(23):8992. PMID: 33256181.
4. Iwata J (2020) Gene ? environment interplay and microRNAs in cleft lip and cleft palate. Oral Science International (2020).
5. Iwata J (2020) Regulatory mechanism of salivary protein secretion. Japanese Association of Oral Science (2020).
6. Suzuki A and Iwata J (2018) Molecular regulatory mechanism of exocytosis in the salivary glands. International Journal of Molecular Sciences. 2018 Oct 17;19(10):3208. PMID: 30336591.
7. Suzuki A, Sangani DR, Ansari A, and Iwata J (2016) Molecular mechanism of midfacial developmental defects. Developmental Dynamics, Mar;245(3):276-93. PMID: 26562615.
8. Suzuki A and Iwata J (2016) Mouse genetic models for temporomandibular joint development and disorders. Oral Diseases, Jan;22(1):33-38. PMID: 26096083.
9. Sangani D, Suzuki A, VonVille H, Hixson JE, and Iwata J (2015) Gene mutations associated with temporomandibular joint disorders: a systematic review. Open Access Library Journal, Doi:10.4236/oalib.1101583.
10. Suzuki A and Iwata J (2015) WNT signaling mechanism in muscle development and homeostasis. Journal of Nature and Science. 2015; 1 (8): e143.
11. Suzuki A, Sangani DR, and Iwata J (2014) Molecular mechanism of cranial neural crest cell development. Journal of Dentistry and Clinical Research, October, 1 (1): 005.
12. Suzuki A and Iwata J (2014) Genetic and environmental risk factors for cleft lip and cleft palate. Progressive Science, 1:e01. doi: 10.14721/pscience.2014.e01.
13. Iwata J, Parada C, and Chai Y. (2011) The mechanism of TGF-β signaling during palate formation: a novel target for prevention of cleft palate. Oral Diseases, Nov; 17 (8): 733-744.
14. Iwata J, Kawakubo T, and Yamamoto K. (2004) Angiostatin. Connective Tissue, 36 (3), 165-169.
1941 East Road, BBS 4208
Houston, TX 77054
Tel: 713-486-2641 (Office)
Tel: 713-486-2678 (Lab)