ORCID |
Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta (TGF-β) family, regulate a wide range of biological processes in development and disease. Although BMPs are best known for their roles in bone formation, their effects vary greatly depending on cell type and context. For example, BMP4 helps maintain mouse embryonic stem cells (ESCs) in a naïve state, but promotes differentiation in other pluripotent stem cells, including human ESCs and mouse epiblast stem cells (EpiSCs). My research uses genomic and sequencing-based approaches to understand how BMPs produce these context-dependent effects in different cells.
As part of this work, I have organized a SMAD Binding Resource, a curated collection of public datasets on SMAD binding with browser-ready tracks for comparative inspection. This resource was prepared as a practical entry point for meta-analysis of signal-dependent transcription factor datasets, because their interpretation requires more than listing binding sites and must take into account stimulation time course, cell type, and experimental context.
In one project, I studied how BMPs function in mouse ESCs in two pluripotent states, naïve and primed. Our findings showed that the BMP-SMAD pathway is not essential for maintaining naïve ESCs. I am now studying how this signaling pathway affects cell fate choices during differentiation into specialized cell types, using single-cell RNA sequencing.
Another focus of my work is on endothelial cells, which line the inside of blood vessels. Disruption of BMP signaling in these cells can lead to vascular diseases such as hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH). I have used chromatin immunoprecipitation followed by sequencing (ChIP-seq) to study how SMAD proteins, key mediators of BMP signaling, bind to DNA and regulate genes. I have also examined ATOH8, a direct target of SMAD1/5. Our findings suggest that ATOH8 may help protect endothelial cells from hypoxic stress and may thereby reduce the risk of PAH. In collaboration with Dr. Maeda at Kagoshima University, we also found that ATOH8 plays a role in adult bone remodeling.
Lastly, I developed a therapeutic protein, FSTL3-Fc, to increase muscle mass by targeting specific members of the TGF-β family, including myostatin (GDF8), GDF11, and activins. We found that a modified form of FSTL3-Fc remained in the circulation longer and significantly increased muscle mass in both healthy mice and a mouse model of Duchenne muscular dystrophy. This approach may provide an alternative to current anti-myostatin therapies, which have shown limitations in clinical trials.
| 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 | Postdoctoral 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 |
| 2006-2007 | Hematology Fellow, The University of Tokyo Hospital, Tokyo, Japan |
| 2004-2006 | Junior Resident (PGY1–2) in Internal Medicine, The University of Tokyo Hospital, Tokyo, Japan |
| 2007-2011 | Ph.D. in Medicine, Graduate School of Medicine, The University of Tokyo (Supervisor: Prof. Kohei Miyazono) |
| 1998-2004 | M.D., The University of Tokyo |
| 2024 | Research grant from The Naito Foundation |
| 2023 | Research grant from the Takeda Science Foundation |
| 2023 | Research grant from The Mochida Memorial Foundation for Medical and Pharmaceutical Research |
| 2021 | Award for the Best Short Talk, virtual FASEB Science Research Conference, The TGF-β Superfamily Conference: Signaling in Development and Disease Certificate |
| 2014 | Best Poster Award, TGF-β meeting in Leiden 2014 Certificate |
| 2013 | Scholarship for Research Abroad from Saga prefecture: ITO Genboku and SAGARA Chian Memorial Scholarship |
| 2012 | Best Poster Award, TGF-β meeting in Leiden 2012 Certificate |
| 2011 | Scholarship for Research Abroad from Kanae Foundation |
| 2011 | Award for the best oral presentation by a young investigator, 9th Hereditary Hemorrhagic Telangiectasia (HHT) Scientific Conference Certificate |
| 2011 | Selected as representative of the doctoral graduating class |
| Oct 2007 | Board Certified Member of the Japanese Society of Internal Medicine #34547 |
| Apr 2004 | Full Medical License (Japan) #438446 |
| Membership: | |
| The Japanese Society of Internal Medicine | |
| The Japanese Biochemical Society | |
| The Molecular Biology Society of Japan | |
| The Japanese Cancer Association | |
| 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, 2011 | 9th 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, 2013 | Center for Human Genetics and VIB Center for the Biology of Disease, KU Leuven, Belgium "Genome-wide mechanisms of BMP/Smad signaling" Morikawa M |