千葉大学大学院医学研究院

小児病態学

千葉大学病院

小児科

① 先天異常症候群の研究：
　Rett症候群，巨脳症-毛細血管奇形症候群，Gorlin症候群，結節性硬化症，神経線維腫症1型を対象として，microRNAやプロテオミクス，疾患iPS研究，脳形態などの臨床的特徴について研究しています。

② ニューロフィードバック研究：
　ADHDに対する経頭蓋直流電流刺激の研究をしています。

③ ヒト脳MRIの網羅的脳形態解析：
　2018年よりハーバード大学ボストン小児病院の高橋恵美博士（現MGH）と共同研究を継続しています。
　また、疾患脳の多施設共同研究の基盤構築を目指して，MRI機種間補正法による小児脳領域の基準値創出研究（BASH Study），正常小児脳における遺伝的・環境的調整因子の解明をめざした，出生コホート研究を用いた脳MRI研究（BIC-B Study）に取り組んでいます。

① 大規模小児コホートを用いた発育関連因子の探索
　（勤務地；千葉）千葉大学予防医科学センター、千葉大学小児科

② 膵β細胞の生理・増殖・再生の研究
　（勤務地；千葉）千葉大学小児科

1. Takatani T, Shirakawa J, Shibue K, Gupta MK, Kim H, Lu S, Hu J, White MF, Kennedy RT, Kulkarni RN. Insulin receptor substrate 1, but not IRS2, plays a dominant role in regulating pancreatic alpha cell function in mice. J Biol Chem. 2021;296:100646.

2. Takatani R, Yoshioka Y, Takahashi T, Watanabe M, Hisada A, Yamamoto M, Sakurai K, Takatani T, Shimojo N, Hamada H, Ochiya T, Mori C. Investigation of umbilical cord serum miRNAs associated with childhood obesity: A pilot study from a birth cohort study. J Diabetes Investig. 2022;13:1740-1744.

3. Takatani T, Eguchi A, Yamamoto M, Sakurai K, Takatani R, Taniguchi Y, Nakayama SF, Mori C, Kamijima M; Japan Environment and Children's Study Group. Individual and mixed metal maternal blood concentrations in relation to birth size: An analysis of the Japan Environment and Children's Study (JECS). Environ Int. 2022;165:107318.

① 腸内細菌叢に着目した川崎病病因の研究　
　（勤務地：千葉・大阪）国立循環器病研究センター研究所、千葉大小児科

② 川崎病冠動脈瘤の発症に関する遺伝学的研究
　（勤務地：千葉）千葉大学公衆衛生学、千葉大学小児科

③ 血小板活性化に着目した川崎病血管障害の発症機序の研究
　（勤務地：千葉）千葉大学小児科、千葉大学実験免疫学

④ 遺伝子多型による重症川崎病患者に対する免疫調節療法の開発
　（勤務地：千葉）千葉大学小児科、千葉大学病院臨床試験部

1. Kobayashi H, Kimura MY, Hasegawa I, Suganuma E, Ikehara Y, Azuma K, et al. Increased Myosin light chain 9 expression during Kawasaki disease vasculitis. Front Immunol. 2022;13:1036672.2.

2. Mitsuishi T, Miyata K, Ando A, Sano K, Takanashi JI, Hamada H. Characteristic nail lesions in Kawasaki disease: Case series and literature review. J Dermatol 2022; 49:232-8.

3. Johnson TA, Mashimo Y, Wu JY, Yoon D, Hata A, Kubo M, et al. Association of an IGHV3-66 gene variant with Kawasaki disease. J Hum Genet. 2021;66(5):475-89.

4. Ae R, Shibata Y, Kosami K, Nakamura Y, Hamada H. Kawasaki Disease and Pediatric Infectious Diseases During the Coronavirus Disease 2019 Pandemic. J Pediatr 2021;239:50-8.

5. Suzuki J, Abe K, Matsui T, Honda T, Yasukawa K, Takanashi JI, et al. Kawasaki Disease Shock Syndrome in Japan and Comparison With Multisystem Inflammatory Syndrome in Children in European countries. Front Pediatr. 2021;9:625456.

6. Hamada H, Suzuki H, Onouchi Y, Ebata R, Terai M, Fuse S, et al. Efficacy of primary treatment with immunoglobulin plus ciclosporin for prevention of coronary artery abnormalities in patients with Kawasaki disease predicted to be at increased risk of non-response to intravenous immunoglobulin (KAICA): a randomised controlled, open-label, blinded-endpoints, phase 3 trial. The Lancet. 2019;393(10176):1128-37.

7. Ebata R, Yasukawa K, Nagai K, Higashi K, Homma J, Takeda N, et al. Sivelestat sodium hydrate treatment for refractory Kawasaki disease patients. Pediatr Int 2019;61:438-43.

① ビタミンD投与によるアレルギー疾患の予防に関する研究（D-PAC）
　（勤務地：千葉）千葉大学小児科

② 重症牛乳アレルギー児を対象としたビタミンD併用効果研究（特定臨床研究）
　（勤務地：千葉）千葉大学小児科

③ 細胞解析、プロテオミクスを用いたアレルギー疾患患者の病態解析
　（勤務地：千葉）かずさDNA研究所、千葉大学小児科

④ 遺伝子、蛋白の網羅的解析手法を用いた小児炎症性疾患の病態解析・バイオマーカー探索研究　
　（勤務地；千葉）かずさDNA研究所、 千葉大学小児科

1. Sato H, Inoue Y, Kawashima Y, Konno R, Ohara O, Kuwana M, et al. In-depth proteomic analysis of juvenile dermatomyositis serum reveals protein expression associated with muscle-specific autoantibodies. Rheumatology (Oxford). 2023.

2. Inoue Y, Yamamoto Y, Suzuki S, Ochiai S, Eguchi A, Nakano T, et al. Maternal and infant serum carotenoids are associated with infantile atopic dermatitis development. Allergy. 2023.

3. Sato N, Yamaide F, Nakano T, Yonekura S, Okamoto Y, Shimojo N. Association of umbilical cord serum TARC/CCL17 with childhood allergies: A birth cohort study. Allergol Int. 2023.

4. Sato H, Inoue Y, Kawashima Y, Nakajima D, Ishikawa M, Konno R, et al. In-Depth Serum Proteomics by DIA-MS with In Silico Spectral Libraries Reveals Dynamics during the Active Phase of Systemic Juvenile Idiopathic Arthritis. ACS Omega. 2022;7(8):7012-23.

5. Yamamoto T, Endo Y, Onodera A, Hirahara K, Asou HK, Nakajima T, et al. DUSP10 constrains innate IL-33-mediated cytokine production in ST2(hi) memory-type pathogenic Th2 cells. Nat Commun. 2018;9(1):4231.

6. Nakano T, Ochiai S, Suzuki S, Yamaide F, Morita Y, Inoue Y, et al. Breastfeeding promotes egg white
sensitization in early infancy. Pediatr Allergy Immunol. 2020;31(3):315-8.

① 急性骨髄性白血病の薬剤代謝SNP解析：臨床検体を用いたSNP解析と臨床情報の統合による予後解析　
　（勤務地；千葉）千葉大学小児科

② 急性白血病に対するNKT細胞療法の開発： NKT細胞のCD1d非依存性腫瘍認識機構の解明　
　（勤務地；千葉）千葉大学免疫細胞医学、千葉大学小児科

③ CAR-iPS-NKT細胞療法の開発　
　（勤務地；横浜）理化学研究所、千葉大学小児科

1. Aoki T, Motohashi S, Koseki H. Regeneration of invariant natural killer T (iNKT) cells: application of iPSC technology for iNKT cell-targeted tumor immunotherapy. Inflamm regen. 43:27-27, 2023

2. Aoki T, Takahashi H, Tomizawa D, et al. Predisposition to prolonged neutropenia after chemotherapy for paediatric acute myeloid leukaemia is associated with better prognosis in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study. Br J Haematol. 193; 176-180, 2021.

3. Aoki T, Takatani T, Motohashi S, et al. Activated invariant natural killer T cells directly recognize leukemia cells in a CD1d-independent manner. Cancer science 111; 2223-2233, 2020.

基礎疾患を有する小児に対するワクチンの効果と安全性に関する研究
　（勤務地：千葉）千葉大学小児科、千葉大学真菌医学研究センター

1. Ishiwada N, Suzuki C, Hasebe S, Tsuchiya A, Takeuchi N, Hishiki H, Sato Y, Sugita K. The effects of health education on health science teachers’ intention to recommend adolescent HPV vaccine for female students in Japan. Hum Vaccin Immunother. 2020; 16: 2752-2757.

2. Takeshita K, Ishiwada N, Takeuchi N, Hishiki H, Hoshino T, Shimojo N. Haemophilus influenzae type b capsular polysaccharide antibody levels in Japanese young patients with hematological malignancies and asplenia J Infect Chemther 2020; 26: 959-62.

3. Hishiki H, Kawashima T, Tsuji NM, Ikari N, Takemura R, Kido H, Shimojo N. A Double-Blind, Randomized, Placebo-Controlled Trial of Heat-Killed Pediococcus acidilactici K15 for Prevention of Respiratory Tract Infections among Preschool Children. Nutrients 2020 ;12(7):1989.

4. Takei H, Takeuchi N, Hoshino T, Ohkusu M, Segawa S, Murata S, Ishiwada N. Bacteriological analysis of Neisseria lactamica isolated from the respiratory tract in Japanese children. J Infect Chemother 2021; 27: 65-69.

5. Takeshita K, Takeuchi N, Ohkusu M, Ohata M, Suehiro M, Maejima H, Abe H, Ohta F, Ohama Y, Tamai K, Haraki M, Ishiwada N.Population-based study of a free rubella-specific antibody testing and immunization campaign in Chiba city in response to the 2018–2019 nationwide rubella outbreak in Japan. Hum Vaccin Immunother. 2021; 17:1779-1784.

6. Ishiwada N, Fujimaki K, Matsumoto T, Kiyota H, Tateda K, Sato J, Hanaki H, Takayanagi R, Yamaguchi Y, Hoshino T, Kuroki H, Iwata S, Tajima T, Horikoshi Y, Shiro H, Bamba M, Kawamura N, Ouchi K, Matsubara K, Okada T, Furuno K, Tsumura N. Nationwide surveillance of bacterial pathogens isolated from children conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2017: General overview of pathogenic antimicrobial susceptibility. J Infect Chemother 2021; 27:139-150.

7. Takeshita K, Takeuchi N, Takahashi Y, Fukasawa C, Hishiki H, Hoshino T, Ishiwada N, Shimojo N. Pneumococcal serotype-specific IgG and opsonophagocytic activity in young Japanese patients with asplenia. Hum Vaccin Immunother. 2021;17(10):3687-3691.

8. Takeshita K, Ishiwada N, Takeuchi N, Ohkusu M, Ohata M, Hino M, Hishiki H, Takeda Y, Sakaida E, Takahashi Y, Shimojo N, Hamada H. Immunogenicity and safety of routine 13-valent pneumococcal conjugate vaccination outside recommended age range in patients with hematological malignancies and solid tumors. Vaccine. 2022;40(9):1238-1245.

9. Takeshita K, Takeuchi N, Ohkusu M, Hishiki H, Shiko Y, Kawasaki Y, Chang B, Ishiwada N. Epidemiological characteristics in serotype 24 paediatric invasive pneumococcal disease according to an 11-year population-based study in Japan. Epidemiol Infect. 2022 Feb 28;150:e66.

10. Kurihara E, Takeshita K, Tanaka S, Takeuchi N, Ohkusu M, Hishiki H, Ishiwada N. Clinical and Bacteriological Analysis of Pediatric Pneumococcal Meningitis after 13-Valent Pneumococcal Conjugate Vaccine Introduction in Japan.　Microbiol Spectr. 2022 Apr 27;10(2):e0182221.

子どもの死因究明、不慮の事故の予防を目的として小児科外来に臨床法医外来を開設し、予防可能な子どもの死について診療・研究を行っています。
　（勤務地：千葉）千葉大学法医学、小児科

先天性疾患、小児期疾患を有した患者の成人診療科との連携や移行の諸問題の抽出とその解決
　（勤務地：千葉）千葉大学小児科、千葉大学病院移行期医療センター