Research topics

Main publications

2025

1．Takahashi M.Four decades of the RET gene: From discovery to tumor-agnostic therapy Journal of the Formosan Medical

　 Association 124: 895-901. (2025)

2．Iida M, Tanaka M, Takagi T, Matsuki T, Kimura K, Shibata, K, Kobayashi Y, Mizutani Y, Kuwamura H, Yamada K, Kitaura H,
Kakita A, Sakakibara M, Asai N, Takahashi M, and Asai M. Girdin deficiency causes developmental and
　 epileptic encephalopathy with hippocampal sclerosis and interneuronopathy Epilepsia. 66: 599-617. (2025)

3．Esaki N, Sakoda T, Ando R, Miyai Y, Iida T, Mizutani Y, Yoshida M, Hara Y, Matsuyama M, Kobayashi T,
　 Shiraki Y, Mii S, Ichikawa J, Kawasaki T, Manabe S, Sakai T, Nishida Y, Takahashi M, Enomoto A.
　 Meflin is a druggable target using antibody-drug conjugates in progressive osteosarcoma.Oncogene. 44:4576-4586. (2025)

4． Mihara K(8th author (after omitting 10 authors)). A novel method for generating chimeric antigenreceptor-transduced primary
　　human naturalkiller cells by the use of multiple cytokines and anti-CD2 and anti-NKp46 stimulatory antibodies. 　
　　Biomed Pharmacother. 2025 191:118505.

5． Mihara K(13th author (after omitting 21 authors)). Monoallelic mutations in MMD2 cause
　　autosomal dominant aggressive periodontitis.J Exp Med. 2025 222(9):e20231911.

6． Mihara K(12th author (after omitting 13 authors)). Chimeric PD‑1 receptor redirects primary T cells
　　against childhood solid tumors but not to PD‑1 ligand‑positive CD80‑coexpressing cells. Mol Med Rep. 2025 32(3):243.

7． Mihara K(1st author (after omitting 5 authors)). The Real World Impact of Immunoglobulin Replacement Therapy
　　on Severe Bacterial Infection for Patients With Hypogammaglobulinemia Secondary to Hematologic Malignancies: A Japanese
　　Claims Database Study. EJHaem. 2025 6(4):e70091.

8． Mihara K(5th author (after omitting 6 authors)). Lipid-siRNA Conjugates Targeting High PD-L1 Expression as Potential Novel
　　Immune Checkpoint Inhibitors. Biomolecules. 2025 15(2):293.

2024

1．Watanabe K, Chiu H, Anderson DJ

　 Whole-brain in situ mapping of neuronal activation in Drosophila during social behaviors and optogenetic

　 stimulation.

　 eLife. 12: RP92380. (2024).

2．Kubo T, Yanagihara K, Nishimura Y, Iino Y, Komatsu T, Tansou R, Mihara K, Seyama T. Antitumor Effect of

　Oleoyl-siRNA against Pancreatic Cancer Using a Portal Vein Infusion Liver-Metastatic Mouse Model.

　Mol Pharm. 221: 5115-5125. (2024)

3．Kawamoto H, Kawase T, Nagano S.

　[Development of off-the-shelf universal T cell therapies from ES/iPS cells: applications in cancer and viral

　 infection].

　 Rinsho Ketsueki. 65: 1075-1086. (2024)

4．Abe-Chayama H, Kawase T, Ichinohe T, Ishida Y, Tateno C, Hijikata M, Chayama K. Hepatitis B virus-specific

　 human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV-infected hepatocytes in

　 mice.

　FEBS Lett. 598: 1354-1365. (2024)

5．Naoi H, Suzuki Y, Miyagi A, Horiguchi R, Aono Y, Inoue Y, Yasui H, Hozumi H, Karayama M, Furuhashi K, Enomoto

　N, Fujisawa T, Inui N, Mii S, Ichihara M, Takahashi M, Suda, T.

　CD109 Attenuates Bleomycin-induced Pulmonary Fibrosis by Inhibiting TGF-b Signaling.

　J Immunol. 212: 1221-1231. (2024)

6．Ando R, Shiraki Y, Miyai Y, Shimizu H, Furuhashi K, Minatoguchi S, Kato K, Kato A, Iida T, Mizutani Y, Ito K,

　Asai N, Mii S, Esaki N, Takahashi M, Enomoto A.

　 Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the

　 pancreas.

　 J Pathol. 262: 61-75. (2024)

7．Owaki T, Iida T, Miyai Y, Kato K, Hase T, Ishii M, Ando R, Hinohara K, Akashi T, Mizutani Y, Ishikawa T, Mii

　 S, Shiraki Y, Esaki N, Yamamoto M, Tsukamoto T, Nomura S, Murakami T, Takahashi M, Yuguchi Y et al.

　 Synthetic retinoid-mediated preconditioning of cancer-associated fibroblasts and macrophages improves cancer

　 response to immune checkpoint blockade.

　 Brit J Cancer. 131: 372-386. (2024)

2023

１. Ando1 R, Shiraki Y, Miyai Y, Shimizu H, Furuhashi K, Minatoguchi S, Kato K, Kato A, Iida T, Mizutani Y, Ito K, Asai N, Mii S,
Esaki N, Takahashi M, Enomoto A.
Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the pancreas.
J Pathol. in press (2023)

２．Takahashi M.
RET proto-oncogene.
Molecular Diagnostics of Cancer (Intechopen) Editor: Dr. Pier Paolo Piccaluga

３．Mori N, Esaki N, Shimoyama Y, Shiraki Y, Asai N, Sakai T, Nishida Y, Takahashi M, Enomoto A, Mii S.
Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling.
Pathol Res Pract. 245:154443. (2023)

４．Aono Y, Suzuki Y, Horiguchi R, Inoue Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Mii S, Takahashi M, Suda T.
CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation.
Am J Respir Cell Mol Biol. 68:201-212. (2023)

5．Sato T, Yamanaka Y, Ueno M, Sotozono C.
Extra Eyelid-Derived Muscle Stem Cells.
Methods Mol Biol. 2640:13-19. (2023)

6．Imai H, Kawase T, Yoshida S, Mese T, Roh S, Fujita A, Uchiki T, Sasaki A, Nagamatsu S, Takazawa A, Ichinohe T, Koshima I.
　　Peripheral T cell profilingreveals downregulated exhaustion marker and increased diversity in lymphedema post-lymphatic
　　venous anastomosis. iScience.
　　2023;26(6):106822.

7. Ito Y, Yamagata M, Yamamoto Y, Hirasaka K, Nikawa T, Sato T.
The reciprocal regulation between mitochondrial-associated membranes and Notch signaling in skeletal muscle atrophy.
eLife, 12:RP89381.doi:10.7554/eLife.89381.(2023)

2022

1. Okamoto A., Fujigaki H., Iriyama C., Goto N., Yamamoto H., Mihara K., Inaguma Y., Miura Y., Furukawa K., Yamamoto Y., Akatsuka Y., Kasahara S., Miyao K., Tokuda M., Sato S., Mizutani Y., Osawa M., Hattori K., Iba S., Kajiya R, Okamoto M., Saito K. and Tomita A.
CD19-positive lymphocyte count is critical for acquisition of anti-SARS-CoV-2 IgG after vaccination in B-cell lymphoma.
Blood Adv. 6: 3230-3233 (2022).

2. Iida T., Mizutani Y., Esaki N., Ponik S.M., Burkel B.M., Weng L., Kuwata K., Masamune A., Ishihara S., Haga H., Kataoka K., Mii S., Shiraki Y., Ishikawa T., Ohno E., Kawashima H., Hirooka Y., Fujishiro M., Takahashi M. and Enomoto A.
Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics.
Oncogene 41: 2764-2777 (2022).

3. Miyai Y., Sugiyama D., Hase T., Asai N., Taki T., Nishida K., Fukui T., Chen-Yoshikawa T.F., Kobayashi H., Mii S., Shiraki Y., Hasegawa Y., Nishikawa H., Ando Y., Takahashi M. and Enomoto A.
Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade.
Life Sci Alliance. 5: e202101230 (2022).

4. Takahashi M.
RET receptor signaling: Function in development, metabolic disease and cancer.
Proc. Japan Acad. Ser. B 98: 112-125. (2022).

5. Kobayashi H., Gieniec K.A., Lannagan T.R.M., Wang T., Asai N., Mizutani Y., Iida T., Ando R., Thomas E.M., Sakai A.,Suzuki N., Ichinose M., Wright J.A., Vrbanac L., Ng J.Q., Goyne J., Radford G., Lawrence M.J., Sammour T., Hayakawa Y., Klebe S., Shin A.E., Asfaha S., Bettington M.L., Rieder F., Arpaia N., Danino T., Butler L.M., Burt A.D., Leedham S.J., Rustgi A.K.., Mukherjee S, Takahashi M., Wang T.C., Enomoto A., Woods S.L. and Worthley D.L.
The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis.
Gastroenterology 162: 890-906. (2022).

6. Ichihara R., Shiraki Y., Mizutani Y., Iida T., Miyai Y., Esaki N., Kato A., Mii S., Ando R., Hayashi M., Takami H., Fujii T., Takahashi M. and Enomoto A.
Matrix remodeling-associated protein 8 is a marker of a subset of cancer-associated fibroblasts in pancreatic cancer.
Pathol Int. 72: 161-175. (2022).

7. Sawada A., Yamamoto T. and Sato T.
Tceal5 and Tceal7 Function in C2C12 Myogenic Differentiation via Exosomes in Fetal Bovine Serum
Int. J. Mol. Sci. 23: 2036 (2022).

8. Igarashi J., Niwa Y. and Sugiyama D.
Research and development of oligonucleotide therapeutics in Japan for rare diseases.
Future Rare Dis. 2: 0008 (2022).

9．Igarashi J, Niwa Y, Sugiyama D
　　Current Opinion on Oligonucleotide Therapeutics for Allergy
　　J Allergy Ther, Vol.13 Iss.5 No:1000285. (2022)

2021

1. Takahashi M., Kobayashi H., Mizutani Y., Hara A., Iida T., Miyai Y., Asai N., Enomoto A.

Roles of the mesenchymal stromal/stem cell marker Meflin/Islr in cancer fibrosis.

Front. Cell Dev. Biol. 9:749924 (2021).

2. Ozono Y., Tamura A., Nakayama S., Herawati E., Hanada Y., Ohata K., Takagishi M., Takahashi M., Imai T., Ohta Y., Oshima K.,
Sato T., Inohara H. and Tsukita S.

Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules.

Sci. Rep. 11: 20224 (2021).

3. Kobayashi H., Gieniec K.A., Ng, J.Q., Goyne, J., Lannagan, T.R.M., Thomas, E.M., Radford, G., Wang, T., Suzuki, N., Ichinose, M.,
Wright, J.A., Vrbanac, L., Burt, A.D., Takahashi, M., Enomoto, A.,
Worthley, D.L. and Woods, S.L.Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma.
J. Vis. Exp. Sep 3;(175) (2021).

4. Yasuda Y., Iwama S., Sugiyama D., Okuji T., Kobayashi T., Ito M., Okada N., Enomoto A., Ito S., Yan Y., Sugiyama M., Onoue T.,
Tsunekawa T., Ito Y., Takagi H., Hagiwara D., Goto M., Suga H., Banno R.,Takahashi M., Nishikawa H. and Arima H.

CD4+ T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in
thyroglobulin-immunized mice.

Sci. Transl. Med. 13: eabb7495 (2021).

5. Nakahara Y., Hashimoto N., Sakamoto K., Enomoto A., Adams T.S., Yokoi T., Omote N., Poli S., Ando A., Wakahara K., Suzuki A.,
Inoue M., Hara A., Mizutani Y., Imaizumi K., Kawabe T., Rosas I.O., Takahashi M., Kaminski N. and Hasegawa Y.

　 Fibroblasts positive for meflin have anti-fibrotic property in pulmonary fibrosis.

　 Eur. Resp. J. 58: 2003397. (2021).

6. Hara A., Kato K., Ishihara T., Kobayashi H., Asai N., Mii S., Shiraki Y., Miyai Y., Ando r., Mizutani Y., Iida T., Takefuji M.,
Murohara T.,Takahashi M. and Enomoto A.

　Meflin defines mesenchymal stem cells and early progenitors with multilineage differentiation capacity across multiple tissues.

　Genes Cells 26: 495-512. (2021)

7. Nakayama S., Yano T., Namba T., Konishi S., Takagishi M., Herawati E., Nishida T., Imoto Y., Ishihara S., Takahashi M., Furuta K.,
Oiwa K., Tamura A. and Tsukita S.

　Planar cell polarity induces local microtubule bundling for coordinated ciliary beating.

　J. Cell Biol. 220: e202010034 (2021).

8. Ohgami N., Iizuka A., Hirai H., Yajima I., Iida M., Shimada A., Tsuzuki T., Jijiwa M., Asai N., Takahashi M. and Kato M.

　Loss-of-function mutation of c-Ret causes cerebellar hypoplasia in mice with Hirschsprung disease and Down's syndrome.

　J. Biol. Chem. 296: 100389 (2021).

9. Isomura H., Taguchi A., Kajino T., Asai N., Nakatochi M., Kato S., Suzuki K., Yanagisawa K., Suzuki M., Fujishita T., Yamaguchi T.,
Takahashi M. and Takahashi T.

　Conditional Ror1 knockout reveals crucial involvement in lung adenocarcinoma development
and identifies novel HIF-1α regulator.

　 Cancer Sci. 112: 1614-1623 (2021).

10. Nakamichi E., Sakakura H., Mii S., Yamamoto N., Hibi H., Asai M. and Takahashi M.

　 Detection of serum/salivary exosomal Alix in patients with oral squamous cell carcinoma.

　 Oral Dis. 27: 439-447 (2021).

11. Hagiwara S., Sasaki E., Hasegawa Y., Suzuki H., Nishikawa D., Beppu S., Terada H., Sawabe M., Takahashi M. and Hanai N.

　 Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma. 　
Cancer Med. 10: 1335-1346 (2021).

12. Kobayashi H., Gieniec K.A., Wright J.A., Wang T., Asai N., Mizutani Y., Ida T., Ando R., Suzuki N., Lannagan T.R.M., Ng J.Q.,
Hara A., Shiraki Y., Mii S., Ichinose M., Vrbanac L., Lawrence M.J., Sammour T., Uehara 　 K., Davies G., Lisowski L.,
Alexander I.E., Hayakawa Y., Butler L.M., Zannettino A.C.W., Din M.O., Hasty J., Burt A.D., Leedham S.J., Rustgi A.K.,
Mukherjee S., Wang T.C., Enomoto A., Takahashi M., Worthley D.L. and Woods S.L. 　
The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. 　
Gastroenterology 160: 1224-1239 (2021).

2020年

1. Esaki N., Enomoto A., Takagishi M., Mizutani Y., Iida T., Ushida K., Shiraki Y., Mii S. and Takahashi M.
The Daple-CK1ε complex regulates Dvl2 phosphorylation and canonical Wnt signaling.
Biochem Biophys Res Commun. 532:406-413 (2020).

2. Chen C., Enomoto A., Weng L., Taki T., Shiraki Y., Mii S., Ichihara R., Kanda M., Koike M., Kodera Y. and Takahashi M.
Complex roles of the actin-binding protein Girdin/GIV in DNA damage-induced apoptosis of cancer cells.
Cancer Sci. 111: 4303-4317 (2020).

3. Taki T., Shiraki Y., Enomoto A., Weng L., Chen C., Asai N., Murakumo Y., Yokoi K., Takahashi M. and Mii S.
CD109 regulates in vivo tumor invasion in lung adenocarcinoma through TGF-β signaling.
Cancer Sci. 111: 4616-4628 (2020).

4. Takagishi M., Esaki N., Takahashi K. and Takahashi M.
Cytoplasmic Dynein Functions in Planar Polarization of Basal Bodies within Ciliated Cells.
iScience 23:101213 (2020).

5. Iida M., Tazaki A., Yajima I., Ohgami N., Taguchi N., Goto Y., Kumasaka Y.M., Prevost-Blondel A., Kono M., Akiyama M., Takahashi M. and Kato M.
Hair graying with aging in mice carrying oncogenic RET
Aging Cell 19: e13273 (2020).

6. Kawai K. and Takahashi M.
Intracellular RET signaling pathways activated by GDNF.
Cell Tissue Res. 382:113-123 (2020).

7. Takahashi M., Kawai K. and Asai N.
Roles of the RET Proto-oncogene in Cancer and Development
JMA J. 3: 175-181 (2020).