Gastroenterology, Hepatology and Nutrition
Takebe Lab

Takebe Research Lab

Modeling Complex Human Development Towards Therapy

On the basis of "reverse reduction-ism based approach," the Takebe Laboratory investigates:

  1. The deductive development of a complex human organoid model
  2. The multidisciplinary dissection of self-driven mechanisms of organogenesis
  3. The technology prototyping towards drug discovery/transplant applications

Through these efforts, with a major focus on foregut- and midgut-derived systems, our lab aims to contribute to human health by establishing new therapies especially for treating pediatric intractable disease.

Also, Dr Takebe holds a joint appointment at the Department of Regenerative Medicine, Yokohama City University in Japan, where he directs a translational program of human induced pluripotent stem cell (iPSC) based liver bud based approach for congenital liver disorders by developing a cGMP manufacturing platform.

Stem cell biology and organoid biology: Think Radically graphic.

Publications

Lansing, F; Mukhametzyanova, L; Rojo-Romanos, T; Iwasawa, K; Kimura, M; Paszkowski-Rogacz, M; Karpinski, J; Grass, T; Sonntag, J; Schneider, PM; Rodriguez-Muela, N; Knöfler, R; Takebe, T; Buchholz, F. Correction of a Factor VIII genomic inversion with designer-recombinases. Nature Communications. 2022; 13:422.

Kimura, M; Iguchi, T; Iwasawa, K; Dunn, A; Thompson, WL; Yoneyama, Y; Chaturvedi, P; Zorn, AM; Wintzinger, M; Quattrocelli, M; Myers, RP; Subramanian, GM; Hwa, V; Takebe, T. En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH. Cell. 2022; 185:4216-4232.e16.

Okabe, R; Chen-Yoshikawa, TF; Yoneyama, Y; Yokoyama, Y; Tanaka, S; Yoshizawa, A; Thompson, WL; Kannan, G; Kobayashi, E; Date, H; Takebe, T. Mammalian enteral ventilation ameliorates respiratory failure. Med. 2021; 2:773-783.e5.

Marsee, A; Roos, FJ M; Verstegen, MM A; Clevers, H; Vallier, L; Takebe, T; Huch, M; Peng, WC; Forbes, SJ; Lemaigre, F; Hu, H; Fuchs, S; Hendriks, D; van der Laan, LJ W. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell. 2021; 28:816-832.

Shinozawa, T; Kimura, M; Cai, Y; Saiki, N; Yoneyama, Y; Ouchi, R; Koike, H; Maezawa, M; Zhang, RR; Dunn, A; Lewis, K; Thompson, WL; Asai, A; Takebe, T. High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids. Gastroenterology. 2021; 160:831-846.e10.

Han, L; Chaturvedi, P; Kishimoto, K; Koike, H; Nasr, T; Iwasawa, K; Giesbrecht, K; Witcher, PC; Eicher, A; Haines, L; Morimoto, M; Wells, JM; Takebe, T; Zorn, AM. Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis. Nature Communications. 2020; 11:4158.

Koido, M; Kawakami, E; Fukumura, J; Noguchi, Y; Ohori, M; Nio, Y; Nicoletti, P; Aithal, GP; Daly, AK; Watkins, PB; Anayama, H; Dragan, Y; Shinozawa, T; Takebe, T. Polygenic architecture informs potential vulnerability to drug-induced liver injury. Nature Medicine. 2020; 26:1541-1548.

Koike, H; Iwasawa, K; Ouchi, R; Maezawa, M; Giesbrecht, K; Saiki, N; Ferguson, A; Kimura, M; Thompson, WL; Wells, JM; Zorn, AM; Takebe, T. Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary. Nature. 2019; 574:112-116.

Ouchi, R; Togo, S; Kimura, M; Shinozawa, T; Koido, M; Koike, H; Thompson, W; Karns, RA; Mayhew, CN; McGrath, PS; Akazawa, C; Yoshikawa, HY; Wells, JM; Takebe, T. Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids. Cell Metabolism. 2019; 30:374-384.e6.

Takebe, T; Wells, JM. Organoids by design. Science. 2019; 364:956-959.

Takahashi, Y; Sekine, K; Kin, T; Takebe, T; Taniguchi, H. Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic Transplantation. Cell Reports. 2018; 23:1620-1629.

Camp, JG; Sekine, K; Gerber, T; Loeffler-Wirth, H; Binder, H; Gac, M; Kanton, S; Kageyama, J; Damm, G; Seehofer, D; Ayabe, H; Taniguchi, H; Takebe, T; Treutlein, B. Multilineage communication regulates human liver bud development from pluripotency. Nature. 2017; 546:533-538.

Takebe, T; Enomura, M; Yoshizawa, E; Kimura, M; Koike, H; Ueno, Y; Matsuzaki, T; Yamazaki, T; Toyohara, T; Osafune, K; Nakauchi, H; Yoshikawa, HY; Taniguchi, H. Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation. Cell Stem Cell. 2015; 16:556-565.

Takebe, T; Sekine, K; Enomura, M; Koike, H; Kimura, M; Ogaeri, T; Zhang, R; Ueno, Y; Zheng, Y; Koike, N; Aoyama, S; Adachi, Y; Taniguchi, H. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013; 499:481-484.

Poling, HM; Sundaram, N; Fisher, GW; Singh, A; Shiley, JR; Nattamai, K; Govindarajah, V; Cortez, AR; Krutko, MO; Ménoret, S; Mayhew, CN; Takebe, T; Mahe, MM; Helmrath, MA. Human pluripotent stem cell-derived organoids repair damaged bowel in vivo. Cell Stem Cell. 2024; 31:1513-1523.e7.

Sheth, M; Sharma, M; Lehn, M; Reza, HA; Takebe, T; Takiar, V; Wise-Draper, T; Esfandiari, L. Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids. APL Bioengineering. 2024; 8:036106.

Kang, SY; Kimura, M; Shrestha, S; Lewis, P; Lee, S; Cai, Y; Joshi, P; Acharya, P; Liu, J; Yang, Y; Alsberg, E; Wells, JM; Takebe, T; Lee, MY. A Pillar and Perfusion Plate Platform for Robust Human Organoid Culture and Analysis. Advanced healthcare materials. 2024; 13:e2302502.

Kimura, M; Takebe, T. Cellotype-phenotype associations using 'organoid villages'. Trends in Endocrinology and Metabolism. 2024; 35:462-465.

Nishimura, T; Takebe, T. Synthetic human gonadal tissues for toxicology. Reproductive Toxicology. 2024; 126:108598.

Osonoi, S; Takebe, T. Organoid-guided precision hepatology for metabolic liver disease. Journal of Hepatology. 2024; 80:805-821.

Naraoka, Y; Mabuchi, Y; Kiuchi, M; Kumagai, K; Hisamatsu, D; Yoneyama, Y; Takebe, T; Akazawa, C. Quality Control of Stem Cell-Based Cultured Meat According to Specific Differentiation Abilities. Cells. 2024; 13:135.

Reza, HA; Farooqui, Z; Reza, AA; Conroy, C; Iwasawa, K; Ogura, Y; Okita, K; Osafune, K; Takebe, T. Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids. Stem Cell Reports. 2023; 18:2071-2083.

Múnera, JO; Kechele, DO; Bouffi, C; Qu, N; Jing, R; Maity, P; Enriquez, JR; Han, L; Campbell, I; Mahe, MM; Hu, YC; Takebe, T; Helmrath, MA; Wells, JM. Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell. 2023; 30:1434-1451.e9.

Kawakami, E; Saiki, N; Yoneyama, Y; Moriya, C; Maezawa, M; Kawamura, S; Kinebuchi, A; Kono, T; Funata, M; Sakoda, A; Itoh, Y; Takayama, K; Nio, Y; Takebe, T. Complement factor D targeting protects endotheliopathy in organoid and monkey models of COVID-19. Cell Stem Cell. 2023; 30:1315-1330.e10.

Matsuzaki, T; Kawano, Y; Horikiri, M; Shimokawa, Y; Yamazaki, T; Okuma, N; Koike, H; Kimura, M; Kawamura, R; Yoneyama, Y; Nakauchi, H; Taniguchi, H; Takebe, T; Yoshikawa, HY. Preparation of mechanically patterned hydrogels for controlling the self-condensation of cells. Star Protocols. 2023; 4:102471.

Tamaoki, N; Siebert, S; Maeda, T; Ha, NH; Good, ML; Huang, Y; Vodnala, SK; Haro-Mora, JJ; Uchida, N; Tisdale, JF; Robey, PG; Kruhlak, MJ; Restifo, NP; Vizcardo, R. Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from induced pluripotent stem cells. Cell Reports: Methods. 2023; 3:100460.

Wu, Y; Oda, M; Hayashi, Y; Kawamura, S; Takebe, T; Mori, K. (2023) Thrombosis region extraction and quantitative analysis in confocal laser scanning microscopic image sequence in in-vivo imaging. SPIE, the international society for optics and photonics. 12468:124680f-124680f-7.

Fujii, T; Yoneyama, Y; Kinebuchi, A; Ozeki, N; Maeda, S; Saiki, N; Chen-Yoshikawa, TF; Date, H; Nishiwaki, K; Takebe, T. Enteral liquid ventilation oxygenates a hypoxic pig model. iScience. 2023; 26:106142.

Mizuno, M; Matsuzaki, T; Ozeki, N; Katano, H; Koga, H; Takebe, T; Yoshikawa, HY; Sekiya, I. Cell membrane fluidity and ROS resistance define DMSO tolerance of cryopreserved synovial MSCs and HUVECs. Stem Cell Research and Therapy. 2022; 13:177.

Lansing, F; Mukhametzyanova, L; Rojo-Romanos, T; Iwasawa, K; Kimura, M; Paszkowski-Rogacz, M; Karpinski, J; Grass, T; Sonntag, J; Schneider, PM; Rodriguez-Muela, N; Knöfler, R; Takebe, T; Buchholz, F. Correction of a Factor VIII genomic inversion with designer-recombinases. Nature Communications. 2022; 13:422.

Kishimoto, K; Iwasawa, K; Sorel, A; Ferran-Heredia, C; Han, L; Morimoto, M; Wells, JM; Takebe, T; Zorn, AM. Directed differentiation of human pluripotent stem cells into diverse organ-specific mesenchyme of the digestive and respiratory systems. Nature Protocols. 2022; 17:2699-2719.

Kimura, M; Iguchi, T; Iwasawa, K; Dunn, A; Thompson, WL; Yoneyama, Y; Chaturvedi, P; Zorn, AM; Wintzinger, M; Quattrocelli, M; Myers, RP; Subramanian, GM; Hwa, V; Takebe, T. En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH. Cell. 2022; 185:4216-4232.e16.

Matsuzaki, T; Shimokawa, Y; Koike, H; Kimura, M; Kawano, Y; Okuma, N; Kawamura, R; Yoneyama, Y; Furuichi, Y; Hakuno, F; Nakauchi, H; Taniguchi, H; Takebe, T; Yoshikawa, HY. Mechanical guidance of self-condensation patterns of differentiating progeny. iScience. 2022; 25:105109.

Lee, IS; Takebe, T. Narrative engineering of the liver. Current Opinion in Genetics and Development. 2022; 75:101925.

Jurickova, I; Bonkowski, E; Angerman, E; Novak, E; Huron, A; Akers, G; Iwasawa, K; Braun, T; Hadar, R; Hooker, M; Takebe, T; Mollen, KP; Haberman, Y; Denson, LA. Eicosatetraynoic Acid and Butyrate Regulate Human Intestinal Organoid Mitochondrial and Extracellular Matrix Pathways Implicated in Crohn's Disease Strictures. Inflammatory Bowel Diseases. 2022; 28:988-1003.

Wu, Y; Oda, M; Hayashi, Y; Takebe, T; Nagata, S; Wang, C; Mori, K. (2022) Blood Vessel Segmentation from Low-Contrast and Wide-Field Optical Microscopic Images of Cranial Window by Attention-Gate-Based Network. Institute of Electrical and Electronics Engineers (IEEE). 00:1863-1872.

Dunn, AW; Cai, Y; Iwasawa, K; Kimura, M; Takebe, T. Synthesis and application of POLYseq for profiling human liver organoids. Star Protocols. 2021; 2:100976.

Iwasawa, K; Takebe, T. Organogenesis in vitro. Current Opinion in Cell Biology. 2021; 73:84-91.

Lewis, K; Yoshimoto, M; Takebe, T. Fetal liver hematopoiesis: from development to delivery. Stem Cell Research and Therapy. 2021; 12:139.

Fang, H; Geng, S; Hao, M; Chen, Q; Liu, M; Liu, C; Tian, Z; Wang, C; Takebe, T; Guan, JL; Chen, Y; Guo, Z; He, W; Diao, J. Simultaneous Zn2+ tracking in multiple organelles using super-resolution morphology-correlated organelle identification in living cells. Nature Communications. 2021; 12:109.

Reza, HA; Okabe, R; Takebe, T. Organoid transplant approaches for the liver. Transplant International. 2021; 34:2031-2045.

Naraoka, Y; Mabuchi, Y; Yoneyama, Y; Suto, EG; Hisamatsu, D; Ikeda, M; Ito, R; Nakamura, T; Takebe, T; Akazawa, C. Isolation and Characterization of Tissue Resident CD29-Positive Progenitor Cells in Livestock to Generate a Three-Dimensional Meat Bud. Cells. 2021; 10:2499.

Dunn, A; Cai, Y; Iwasawa, K; Kimura, M; Takebe, T. POLYseq: A poly(β-amino ester)-based vector for multifunctional cellular barcoding. Stem Cell Reports. 2021; 16:2149-2158.

Okabe, R; Chen-Yoshikawa, TF; Yoneyama, Y; Yokoyama, Y; Tanaka, S; Yoshizawa, A; Thompson, WL; Kannan, G; Kobayashi, E; Date, H; Takebe, T. Mammalian enteral ventilation ameliorates respiratory failure. Med. 2021; 2:773-783.e5.

Marsee, A; Roos, FJ M; Verstegen, MM A; Clevers, H; Vallier, L; Takebe, T; Huch, M; Peng, WC; Forbes, SJ; Lemaigre, F; Hu, H; Fuchs, S; Hendriks, D; van der Laan, LJ W. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell. 2021; 28:816-832.

Dobrindt, K; Hoagland, DA; Seah, C; Kassim, B; O'Shea, CP; Murphy, A; Iskhakova, M; Fernando, MB; Powell, SK; Deans, PJ M; Huckins, LM; tenOever, BR; Akbarian, S; Brennand, KJ. Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection. Stem Cell Reports. 2021; 16:505-518.

Annabi, N; Baker, M; Boettiger, A; Chakraborty, D; Chen, Y; Corbett, KS; Correia, B; Dahlman, J; de Oliveira, T; Ertuerk, A; Takebe, T; Vandenberghe, LH; Varshney, RK; Wang, J. Voices of biotech research. Nature Biotechnology. 2021; 39:281-286.

Hayashi, H; Osaka, S; Sakabe, K; Fukami, A; Kishimoto, E; Aihara, E; Sabu, Y; Mizutani, A; Kusuhara, H; Naritaka, N; Mayhew, C; Setchell, K; Takebe, T; Asai, A. Modeling Human Bile Acid Transport and Synthesis in Stem Cell-Derived Hepatocytes with a Patient-Specific Mutation. Stem Cell Reports. 2021; 16:309-323.

Shinozawa, T; Kimura, M; Cai, Y; Saiki, N; Yoneyama, Y; Ouchi, R; Koike, H; Maezawa, M; Zhang, RR; Dunn, A; Lewis, K; Thompson, WL; Asai, A; Takebe, T. High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids. Gastroenterology. 2021; 160:831-846.e10.

Koike, H; Iwasawa, K; Ouchi, R; Maezawa, M; Kimura, M; Kodaka, A; Nishii, S; Thompson, WL; Takebe, T. Engineering human hepato-biliary-pancreatic organoids from pluripotent stem cells. Nature Protocols. 2021; 16:919-936.

Thompson, WL; Takebe, T. Human liver model systems in a dish. Development, Growth and Differentiation. 2021; 63:47-58.

Funata, M; Nio, Y; Erion, DM; Thompson, WL; Takebe, T. The promise of human organoids in the digestive system. Cell Death and Differentiation. 2021; 28:84-94.

YONEYAMA, Y; OKABE, R; TAKEBE, T. Enteral ventilation technology to combat severe respiratory failure. 2021; 3:93-97.

Han, L; Chaturvedi, P; Kishimoto, K; Koike, H; Nasr, T; Iwasawa, K; Giesbrecht, K; Witcher, PC; Eicher, A; Haines, L; Morimoto, M; Wells, JM; Takebe, T; Zorn, AM. Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis. Nature Communications. 2020; 11:4158.

Sekine, K; Ogawa, S; Tsuzuki, S; Kobayashi, T; Ikeda, K; Nakanishi, N; Takeuchi, K; Kanai, E; Otake, Y; Okamoto, S; Kobayashi, T; Takebe, T; Taniguchi, H. Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media. Scientific Reports. 2020; 10:17937.

Koido, M; Kawakami, E; Fukumura, J; Noguchi, Y; Ohori, M; Nio, Y; Nicoletti, P; Aithal, GP; Daly, AK; Watkins, PB; Anayama, H; Dragan, Y; Shinozawa, T; Takebe, T. Polygenic architecture informs potential vulnerability to drug-induced liver injury. Nature Medicine. 2020; 26:1541-1548.

Kobayashi, N; Togo, S; Matsuzaki, T; Hashiseko, K; Kawamura, R; Suganuma, M; Nakabayashi, S; Yoneyama, Y; Ouchi, R; Takebe, T; Yoshikawa, HY. Stiffness distribution analysis in indentation depth direction reveals clear mechanical features of cells and organoids by using AFM. Applied Physics Express. 2020; 13:097001.

Okabe, R; Chen-Yoshikawa, TF; Yoshizawa, A; Hirashima, T; Saito, M; Date, H; Takebe, T. Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice. European Journal of Cardio-Thoracic Surgery. 2020; 58:638-645.

Sakabe, K; Takebe, T; Asai, A. Organoid Medicine in Hepatology. Clinical Liver Disease. 2020; 15:3-8.

Thompson, WL; Takebe, T. Generation of multi-cellular human liver organoids from pluripotent stem cells. Methods in Cell Biology. : Elsevier; Elsevier; 2020.

Iizuka, S; Nishii, S; Tanimoto, E; Nakazawa, H; Kodaka, A; Takebe, T. Waiting Time Analysis at University Hospitals Based on Visitor Psychology. Lecture Notes in Computer Science. 2020; 12184:212-221.

Science Blog

Takebe Receives Vilcek Foundation Award for Creative Promise
Organoids

Takebe Receives Vilcek Foundation Award for Creative Promise

Takanori Takebe, MD, PhD2/6/2024

Engineered Organoids Might Serve as Bridge to Liver Transplantation in Severe Jaundice
Organoids

Engineered Organoids Might Serve as Bridge to Liver Transplantation in Severe Jaundice

Takanori Takebe, MD, PhD10/23/2023

Human Vascular Organoids Reveal Clues for a Potential COVID Treatment
Organoids

Human Vascular Organoids Reveal Clues for a Potential COVID Treatment

Takanori Takebe, MD, PhD10/5/2023

JSPS PRIZE Recipient

Dr. Takanori Takebe was selected as one of six young Japanese researchers to receive the JSPS PRIZE. The Japan Society for the Promotion of Science (JSPS) offers this annual award to recognize and support young researchers with superlative research abilities in early stages of their careers. Recipients have the potential to become world leaders in their fields. Dr. Takebe will receive the award from the Imperial Prince of Japan in February 2019. Learn more about PRIZE

Contact Us

A photo of Takanori Takebe.

Takanori Takebe, MD
Assistant Professor, UC Department of Pediatrics

Mailing Address
Division of Gastroenterology, Hepatology and Nutrition &  Division of Developmental Biology
3333 Burnet Ave.
MLC 2010
Cincinnati, OH 45229-3039 

Lab: Location R, Room 3543 

Office: Location S, Suite S3.622

Phone: 513-803-7807 
Fax: 513-636-5581
Email: Takanori.Takebe@cchmc.org

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