Japanese version

CURRICULUM VITAE

Name: Masato Morikawa
Date of Birth: August 23, 1979
Citizenship: Japan

ORCIDORCID

CONTACT INFORMATION:

Division of Health Science,
Advanced Comprehensive Research Organization (ACRO),
Teikyo University

2-21-1 Kaga, Itabashi, Tokyo, 173-0003, Japan
e-mail: address

SUMMARY

Bone morphogenetic proteins (BMPs) regulate various physiological and pathological processes, in addition to their role in inducing bone formation. It is widely accepted that the biological effects of BMPs are cell-type-specific and context-dependent. In the field of stem cell research, for example, BMP4 sustains the self-renewal of naïve mouse embryonic stem cells (ESCs), while promoting differentiation in other pluripotent stem cell types, including primed human ESCs. Using next-generation sequencing (NGS) technologies, my objective is to uncover the molecular mechanisms behind the cell-type-specific effects of BMPs.

First, my focus is on vascular endothelial cells (ECs). Disruptions in this signaling pathway can lead to genetic vascular diseases, such as hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH). Our research group conducted ChIP-seq experiments on SMAD transcription factors, elucidating how SMAD recognizes its target sites on the genome. Furthermore, we have performed a functional analysis of the transcription factor ATOH8, a direct target of SMAD1/5. Interestingly, our findings suggest that ATOH8 may counteract hypoxic signaling in ECs, thereby preventing the development of PAH. Additionally, we have demonstrated that ATOH8 plays a role in regulating bone remodeling in adult bones through collaboration with Dr. Maeda at Kagoshima University.

Second, I revisited the role of BMPs in mouse ESCs maintained in two different pluripotent states: naïve and primed. We demonstrated that the BMP-SMAD pathway is dispensable for maintaining naïve pluripotency. Currently, we are focusing on the roles of the SMAD pathway during differentiation and cell fate decisions of mouse ESCs.

Lastly, I developed an activin/myostatin/GDF11-selective ligand trap, FSTL3-Fc. Myostatin (MSTN), also known as growth differentiation factor 8 (GDF8), acts as an inhibitor of normal muscle growth. Additionally, GDF11 and activins redundantly function as negative regulators of muscle growth. We discovered that the monovalent form of FSTL3-Fc has a longer serum half-life and induces systemic muscle hypertrophy in WT mice and a mouse model of Duchenne muscular dystrophy. We believe that monovalent FSTL3-based therapy addresses the challenges associated with current anti-myostatin therapies.

EMPLOYMENT HISTORY

2022－Present Associate Professor, Advanced Comprehensive Research Organization (ACRO), Teikyo University, Tokyo, Japan
2016－2022 Assistant Professor, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
2012－2015 Post-doctoral fellow, Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden
2011－2012 Project Assistant Professor, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
2006－2007Fellow in Hematology, The University of Tokyo Hospital, Tokyo, Japan
2004－2006Resident in Internal Medicine, The University of Tokyo Hospital, Tokyo, Japan

EDUCATION

2007－2011Ph.D. in Medicine, The University of Tokyo (Supervisor: Prof. Kohei Miyazono)
1998－2004 M.D., The University of Tokyo

HONORS AND AWARDS

2023Research grant from the Takeda Science Foundation
2023Research grant from The Mochida Memorial Foundation for Medical and Pharmaceutical Research
2021Award for the Best Short Talk, virtual FASEB Science Research Conference, The TGF-β Superfamily Conference: Signaling in Development and Disease
Certificate
2014Best Poster Award, TGF-β meeting in Leiden 2014
Certificate
2013Scholarship for Research Abroad from Saga prefecture: ITO Genboku and SAGARA Chian Memorial Scholarship
2012Best Poster Award, TGF-β meeting in Leiden 2012
Certificate
2011Scholarship for Research Abroad from Kanae Foundation
2011Award for the best oral presentation by a young investigator, 9th Hereditary Hemorrhagic Telangiectasia (HHT) Scientific Conference
Certificate
2011Graduated with distinction (Valedictorian)

MEDICAL LICENSURE/BOARD CERTIFICATION

Oct 2007Board Certified Member of the Japanese Society of Internal Medicine #34547
Apr 2004Full Medical License (Japan) #438446

PROFESSIONAL AND SOCIETY MEMBERSHIPS

Membership:
The Japanese Society of Internal Medicine
The Japanese Biochemical Society
The Molecular Biology Society of Japan
The Japanese Cancer Association

PEER-REVIEWED PUBLICATIONS

    Original Research Article (full list)

  1. Ogami T, Tamura Y, Toss K, Yuki K, Morikawa M, Tsutsumi S, Aburatani H, Miyazawa K, Miyazono K, Koinuma D, MAB21L4 regulates the TGF-β-induced expression of target genes in epidermal keratinocytes, J Biochem, 171(4), 399-410, 2022
  2. Tanabe R, Miyazono K, Todo T, Saito N, Iwata C, Komuro A, Sakai S, Raja E, Koinuma D, Morikawa M, Westermark B, Heldin CH, PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A, Mol Oncol, 16(1), 269-288, 2022
  3. Ozawa T, Miyazono K, Morikawa M*, Preparation of monovalent follistatin-like 3-Fc-fusion protein and evaluation of its effects on muscle mass in mice, STAR Protoc, 2(4), 100839, 2021 (*Corresponding author)
  4. Ozawa T, Morikawa M*, Morishita Y, Ogikubo K, Itoh F, Koinuma D, Nygren PÅ, Miyazono K*, Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice, iScience, 24(5), 102488, 2021 (*Co-corresponding author)
    Press Release
  5. Tamura Y, Morikawa M, Tanabe R, Miyazono K, Koinuma D, Anti-pyroptotic function of TGF-β is suppressed by a synthetic dsRNA analogue in triple negative breast cancer cells, Mol Oncol, 15(5), 1289-1307, 2021
  6. Yahiro Y, Maeda S, Morikawa M, Koinuma D, Jokoji G, Ijuin T, Komiya S, Kageyama R, Miyazono K, Taniguchi N, BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts, Bone Res, 8(1), 32, 2020
  7. Sundqvist A, Vasilaki E, Voytyuk O, Bai Y, Morikawa M, Moustakas A, Miyazono K, Heldin CH, ten Dijke P, van Dam H, TGFβ and EGF signaling orchestrates the AP-1- and p63 transcriptional regulation of breast cancer invasiveness, Oncogene, 39(22), 4436-4449, 2020
  8. Hokari S, Tamura Y, Kaneda A, Katsura A, Morikawa M, Murai F, Ehata S, Tsutsumi S, Ishikawa Y, Aburatani H, Kikuchi T, Miyazono K, Koinuma D, Comparative analysis of TTF-1 binding DNA regions in small-cell lung cancer and non-small-cell lung cancer, Mol Oncol, 14(2), 277-293, 2020
  9. Morikawa M, Mitani Y, Holmborn K, Kato T, Koinuma D, Maruyama J, Vasilaki E, Sawada H, Kobayashi M, Ozawa T, Morishita Y, Bessho Y, Maeda S, Ledin J, Aburatani H, Kageyama R, Maruyama K, Heldin CH, Miyazono K, The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension, Sci Signal, 12(607), eaay4430, 2019
    Press Release　　 UTokyo FOCUS
  10. Raja E, Morikawa M, Nishida J, Tanabe R, Takahashi K, Seeherman SJ, Saito N, Todo T, Miyazono K, Tyrosine kinase Eph receptor A6 sensitizes glioma-initiating cells towards bone morphogenetic protein-induced apoptosis, Cancer Sci, 110(11), 3486-3496, 2019
  11. Richter A, Alexdottir MS, Magnus SH, Richter T, Morikawa M, Zwijsen A, Valdimarsdottir G, EGFL7 mediates BMP9-induced sprouting angiogenesis of endothelial cells derived from human embryonic stem cells, Stem Cell Reports, 12(6), 1250-1259, 2019
  12. Harada M, Morikawa M, Ozawa T, Kobayashi M, Tamura Y, Takahashi K, Tanabe M, Tada K, Seto Y, Miyazono K, Koinuma D, Palbociclib enhances activin-SMAD-induced cytostasis in estrogen receptor-positive breast cancer, Cancer Sci, 110(1), 209-220, 2019
  13. Kawasaki N, Isogaya K, Dan S, Yamori T, Takano H, Yao R, Morishita Y, Taguchi L, Morikawa M, Heldin CH, Noda T, Ehata S, Miyazono K, Koinuma D, TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling, Cell Discov, 4, 1, 2018
  14. Komuro A, Raja E, Iwata C, Soda M, Isogaya K, Yuki K, Ino Y, Morikawa M, Todo T, Aburatani H, Suzuki H, Ranjit M, Natsume A, Mukasa A, Saito N, Okada H, Mano H, Miyazono K, Koinuma D, Identification of a novel fusion gene HMGA2-EGFR in glioblastoma, Int J Cancer, 142(8), 1627-1639, 2018
  15. Sundqvist A#, Morikawa M#, Ren J, Vasilaki E, Kawasaki N, Kobayashi M, Koinuma D, Aburatani H, Miyazono K, Heldin CH, van Dam H, ten Dijke P, JUNB governs a feed-forward network of TGFβ signaling that aggravates breast cancer invasion, Nucleic Acids Res, 46(3), 1180-1195, 2018 (#Co-first author)
  16. Katsura A, Tamura Y, Hokari S, Harada M, Morikawa M, Sakurai T, Takahashi K, Mizutani A, Nishida J, Yokoyama Y, Morishita Y, Murakami T, Ehata S, Miyazono K, Koinuma D, ZEB1-regulated inflammatory phenotype in breast cancer cells, Mol Oncol, 11(9), 1241-1262, 2017
  17. Raja E, Komuro A, Tanabe R, Sakai S, Ino Y, Saito N, Todo T, Morikawa M, Aburatani H, Koinuma D, Iwata C, Miyazono K, Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells, Oncogene, 36(35), 4963-4974, 2017
  18. Vasilaki E, Morikawa M, Koinuma D, Mizutani A, Hirano Y, Ehata S, Sundqvist A, Kawasaki N, Cedervall J, Olsson AK, Aburatani H, Moustakas A, Miyazono K, Heldin CH, Ras and TGF-β signaling enhance cancer progression by promoting the ΔNp63 transcriptional program, Sci Signal, 9(442), ra84, 2016
  19. Sakurai T, Isogaya K, Sakai S, Morikawa M, Morishita Y, Ehata S, Miyazono K, Koinuma D, RNA binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma, Oncogene, 35(38), 5000–5009, 2016
  20. Morikawa M, Koinuma D, Mizutani A, Kawasaki N, Holmborn K, Sundqvist A, Tsutsumi S, Watabe T, Aburatani H, Heldin CH, Miyazono K, BMP sustains embryonic stem cell self-renewal through distinct functions of different Krüppel-like factors, Stem Cell Reports, 6(1), 64-73, 2016
    UTokyo FOCUS
  21. Arase M, Horiguchi K, Ehata S, Morikawa M, Tsutsumi S, Aburatani H, Miyazono K, Koinuma D, Transforming growth factor-β-induced lncRNA-Smad7 inhibits apoptosis of mouse breast cancer JygMC(A) cells, Cancer Sci, 105(8), 974-982, 2014
  22. Kaneda A, Fujita T, Anai M, Yamamoto S, Nagae G, Morikawa M, Tsuji S, Oshima M, Miyazono K, Aburatani H, Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence, PLoS Genet, 7(11), e1002359, 2011
  23. Mizutani A, Koinuma D, Tsutsumi S, Kamimura N, Morikawa M, Suzuki HI, Imamura T, Miyazono K, Aburatani H, Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4α in HepG2 cells, J Biol Chem, 286(34), 29848-29860, 2011
  24. Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Kanki Y, Heldin CH, Aburatani H, Miyazono K, ChIP-seq reveals cell type-specific binding patterns of BMP-specific Smads and a novel binding motif, Nucleic Acids Res, 39(20), 8712-8727, 2011
  25. Yoshimatsu Y, Yamazaki T, Mihira H, Itoh T, Suehiro J, Yuki K, Harada K, Morikawa M, Iwata C, Minami T, Morishita Y, Kodama T, Miyazono K, Watabe T, Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1, J Cell Sci, 124(Pt 16), 2753-2762, 2011
  26. Ishiura H, Morikawa M, Hamada M, Watanabe T, Kako S, Chiba S, Motokura T, Hangaishi A, Shibahara J, Akahane M, Goto J, Kwak S, Kurokawa M, Tsuji S, Lymphomatoid granulomatosis involving central nervous system successfully treated with rituximab alone, Arch Neurol, 65(5), 662-665, 2008
  27. Ohka S, Matsuda N, Tohyama K, Oda T, Morikawa M, Kuge S, Nomoto A, Receptor (CD155)-dependent endocytosis of poliovirus and retrograde axonal transport of the endosome, J Virol, 78(13), 7186-7198, 2004

    28. Review Articles

  28. Miyazono K, Katsuno Y, Koinuma D, Ehata S, Morikawa M, Intracellular and extracellular TGF-β signaling in cancer: some recent topics, Front Med, 12(4), 387-411, 2018
  29. Morikawa M, Derynck R, Miyazono K, TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology, Cold Spring Harb Perspect Biol, 8(5), a021873, 2016
  30. Morikawa M, Koinuma D, Miyazono K, Heldin CH, Genome-wide mechanisms of Smad binding, Oncogene, 32(13), 1609-1615, 2013
  31. Miyazono K, Kamiya Y, Morikawa M, Bone morphogenetic protein receptors and signal transduction, J Biochem, 147(1), 35-51, 2010

LECTURES/CONFERENCE PRESENTATIONS

International:
Oct 12, 2022 13th International BMP Conference, Dubrovnik, Croatia
"Follistatin-like 3-based ligand trap increases muscle mass in mice" (Oral, Invited)
Morikawa M, Miyazono K
July 21, 2021 virtual FASEB Science Research Conference, The TGF-β Superfamily Conference: Signaling in Development and Disease
"Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice" (Selected Poster Oral)
Morikawa M, Ozawa T, Miyazono K
Oct 24, 2018 12th International BMP Conference, Tokyo, Japan
"The ALK-1/SMAD/ATOH8 axis protects against hypoxia and development of pulmonary arterial hypertension" (Oral)
Morikawa M, Mitani Y, Holmborn K, Koinuma D, Kageyama R, Maruyama K, Heldin CH, Miyazono K
Sep 18, 2014 10th International BMP Conference, Berlin, Germany
"Differential roles of BMP-induced Smad and non-Smad signals in naïve mouse ES cells" (Oral, Invited)
Morikawa M, Koinuma D, Heldin CH, Miyazono K
Oct 28, 2013 3rd International Symposium by JSPS Core-to-Core Program, Cooperative International Framework in TGF-β Family Signaling
"Differential roles of BMP signaling in embryonic stem cells" (Oral)
Morikawa M
May 24, 20119th Hereditary Hemorrhagic Telangiectasia (HHT) Scientific Conference, Antalya, Turkey
"Genome-wide analysis of Smad1/5 binding sitesin endothelial cells" (Oral)
Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Heldin CH, Aburatani H, Miyazono K
National:
Mar 6, 2011 4th retreat of Global COE, Integrative Life Science Based on the Study of Biosignaling Mechanisms, Hokuto
"Genome-wide analysis of Smad1/5 binding sitesin endothelial cells" (Oral)
Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Heldin CH, Aburatani H, Miyazono K
Dec 9, 2010 33rd Annual Meeting of the Molecular Biology Society of Japan, Kobe
"Genome-wide analysis of Smad1/5 binding sitesin endothelial cells" (Oral)
Morikawa M, Koinuma D, Tsutsumi S, Vasilaki E, Heldin CH, Aburatani H, Miyazono K
Seminar:
Oct 8, 2013Center for Human Genetics and VIB Center for the Biology of Disease, KU Leuven, Belgium
"Genome-wide mechanisms of BMP/Smad signaling"
Morikawa M

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