Masanobu Komatsu, Ph.D.

Headshot of Masanobu Komatsu
  • Associate Professor of Orthopaedic Surgery

Research Interests

Normalization of pathological vasculature; High endothelial venules associated with tertiary lymphoid structure in cancer; Vascular targeting for drug delivery more


Dr. Komatsu is a Principal Investigator of the Cancer & Blood Disorders Institute, Johns Hopkins All Children's Hospital and an Associate Professor of Orthopaedic Surgery, Johns Hopkins University School of Medicine. He is also affiliated with the Department of Surgery and the Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital. He studies the malformation and malfunction of blood vessels and how these abnormalities impact medical conditions such as cancer, cardiovascular diseases, and infectious diseases. He hopes to discover ways to restore normal function to these blood vessels, which would have a profound effect on the efficacy of treatments.

Dr. Komatsu earned an undergraduate degree in marine science/biology and a Ph.D. in cell biology at the University of Miami, where he also did post-doctoral training in immunology. He continued his post-doctoral study at the Sanford Burnham Prebys Medical Discovery Institute under Dr. Erkki Ruoslahti who discovered cell adhesion molecules such as fibronectin and integrins. In 2005, he became an Assistant Professor of the University of Alabama at Birmingham Department of Pathology, where he began investigating the molecular mechanism of blood vessel formation and stability. He also began working on the development of vascular targeting technologies for target-specific drug delivery and imaging. He joined Sanford Burnham's NCI-designated Cancer Center as a faculty member in 2008 before coming to Johns Hopkins All Children’s Hospital in 2018 to continue his research at Johns Hopkins University. He holds patents related to the vascular regulation by R-RAS and peptide-mediated drug targeting of pulmonary arterial hypertension, sepsis, and cancer. more


  • Associate Professor of Orthopaedic Surgery

Departments / Divisions

Centers & Institutes



  • B.S.; University of Miami (Florida) (1991)
  • Ph.D.; University of Miami Leonard M. Miller School of Medicine (Florida) (1998)

Research & Publications

Research Summary

The mission of Dr. Komatsu’s research is to take a multidisciplinary approach to address important unmet needs in various medical conditions associated with vascular disorders and abnormalities. The broad research background of the group allows them to bring multiple disciplines together to basic research, application, and technology development. The research focus of Dr. Komatsu’s laboratory is twofold. One is to investigate the molecular mechanisms of blood vessel formation, remodeling, and dysfunction. With this knowledge, they search for breakthrough solutions for the treatment of cancer, cardiovascular diseases, and vascular complications in various other conditions. The other research focus is to develop novel vascular targeting strategies for site-specific drug delivery to diseased organs and tissues.

The current research focus of the Komatsu Lab includes the role of the tumor vasculature in shaping the tumor immune landscape – in particular, the role of intratumoral high endothelial venules in facilitating tertiary lymphoid structure (TLS) formation and potentiating anti-tumor immunity. 

In a separate research program, the group investigates endothelial cell and pericyte signaling pathways responsible for the maturation and stability of blood vessels in an effort to find a way to restore normal function to pathologically regenerating or remodeling blood vessels. For the drug targeting focus area, Dr. Komatsu explores the use of specific peptides that selectively target drug delivery to the tumor vasculature, hypertensive pulmonary arteries, or inflamed endothelium in sepsis. 


High endothelial venules as gateways for lymphocyte entry into tumors

High endothelial venules (HEV) are venules specialized for recruiting naïve T and B cells into lymph nodes from the circulation. A subset of cancer patients presents lymph node-like structures called tertiary lymphoid structures (TLS) inside or at the periphery of the tumors. TLS are composed of clusters of accumulating immune cells that contain T cells, B cells, and dendritic cells surrounding HEVs. It is thought that TLS are the recruitment centers for T cells and B cells where these lymphocytes become activated locally by tumor antigens, and the HEVs serve as the main entrance for the recruitment. The densities of TLS and HEVs correlate with favorable clinical outcomes of conventional cancer therapies. The presence of TLS with B cell germinal centers predicts a significant response to anti-PD-1 immune checkpoint inhibition therapies. These clinical observations suggest that increased intratumoral HEV formation allowing lymphocyte recruitment may heighten cancer immunotherapies. The Komatsu lab is investigating the molecular mechanisms of intratumoral HEV formation and developing clinically translatable strategies to induce TLS in malignant tumors.

Regulation of blood vessel maturation and stability

Blood vessel formation and maturation are regulated by the balance between pro-angiogenic and anti-angiogenic signals. Dr. Komatsu’s group has identified a key role for the small GTPase R-Ras in promoting vessel maturation while attenuating excessive angiogenic response in pathologically regenerating vasculature. R-Ras is highly expressed in fully differentiated, quiescent vascular smooth muscle cells, endothelial cells, and pericytes of the mature adult vasculature. Unlike prototypic oncoprotein Ras such as K-Ras, R-Ras inhibits vascular cell proliferation and invasion and promotes vascular quiescence. R-Ras signaling primarily affects vessel remodeling and regeneration by counterbalancing vessel activation. The elevated R-Ras expression normalizes pathologically regenerating vasculature.

There is currently no successful strategy for promoting vascular maturation for therapeutic purposes. The studies conducted by Dr. Komatsu’s group showed that R-Ras coordinates multiple signaling events in endothelial cells and pericytes to redirect nascent vessel formation from angiogenic sprouting to vessel stabilization. The group also showed an important activity of R-Ras to facilitate tubulogenesis (creation of lumen) of growing vessels via non-canonical Akt pathway that stabilizes the microtubule cytoskeleton. The unique multifaceted activities of R-Ras make this Ras homolog an important subject of investigation in search of a new strategy for manipulating blood vessel function.

Innovation in drug delivery technology

The other area of Dr. Komatsu’s research is to develop novel vascular targeting strategies for target-specific drug delivery. Vascular targeting technology takes advantage of unique molecular signatures of blood vessels at specific sites in the body. This technology enables direct delivery of drugs to tumors or other diseased tissues through the vascular network. Since drugs are targeted to specific sites, it is possible to enhance the drug efficacy while substantially reducing the adverse side effects of the drugs. 

Dr. Komatsu’s group succeeded in targeting the lung lesions of pulmonary arterial hypertension. Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary vascular resistance. PAH is a serious lung disorder, which can lead to right heart failure and death. There is currently no effective treatment for PAH. Dr. Komatsu’s group used a 9 amino-acid cyclic peptide, CARSKNKDC (CAR) to selectively target PAH lesions. The unique property of the CAR peptide offers a novel drug delivery system for PAH.

Lab Website: Komatsu Laboratory, Johns Hopkins All Children's Hospital/All Children's Research Institute

Technology Expertise Keywords

Development of vascular targeting technology for organ/lesion-specific drug delivery; Development of vascular imaging technology

Selected Publications

View all on PubMed

Sawada J, Hiraoka N, Qi R, Jiang L, Fournier-Goss AE, Yoshida M, Kawashima H, Komatsu M. Molecular Signature of Tumor-Associated High Endothelial Venules that can Predicts Breast Cancer Survival. Cancer Immunology Research. 2022 online ahead of print, PMID: 35201289

Sawada J, Perrot CY, Chen L, Fournier-Goss AE, Oyer J, Copik A, Komatsu M. High Endothelial Venules Accelerate Naive T Cell Recruitment by Tumor Necrosis Factor-Mediated R-Ras Upregulation. Am J Pathol. 2021; 191(2):396-414. PMID: 33159887

Li F, Sawada J, and Komatsu M. R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature. Nature Communications. 2017; 8(1):1720, PMID: 29170374

Sawada J, Urakami T, Li F, Urakami A, Zhu W, Fukuda M, Li DY, Ruoslahti E, Komatsu M. Small GT Pase R-Ras regulates integrity and functionality of tumor blood vessels. Cancer Cell. 2012 Aug 14;22(2):235-49. doi: 10.1016/j.ccr.2012.06.013. PMID: 22897853

Komatsu M, Ruoslahti E. R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nature Medicine 2005 Dec;11(12):1346-50. PMID: 16286923


R-Ras activity in vascular regulation
Patent # U.S. Patent No. US8506965 B2 | 

CAR Peptide for Homing, Diagnosis & Targeted Therapy for Pulmonary and Fibrotic Disorders
Patent # U.S. Patent No. US9180161 B2 | 

Compositions containing a pharmacophore with selectivity to diseased tissue and methods of making same
Patent # U.S. Patent No. US20190022170A1 | 

Contact for Research Inquiries

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St. Petersburg, FL 33701 map

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Activities & Honors


  • Top 10 most popular science news release of 2017
  • Altmetric Score 98th percentile of all the tracked articles of a similar age in all journals and featured in 21 public news outlets. R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature. Nature Communications, 2017
  • Article selected by the Faculty of 1000. Peptide-Directed Highly Selective Targeting of Pulmonary Arterial Hypertension. American Journal of Pathology, 2011
  • Article selected by the Faculty of 1000. R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nature Medicine, 2005
  • 2001-2002 Ruth L. Kirschstein National Research Service Award, National Institute of Health


  • American Association for Cancer Research
  • American Heart Association
  • North American Vascular Biology Organization
  • American Thoracic Society

Videos & Media

Recent News Articles and Media Coverage

Researchers Probe the New Frontier of Immune Therapy, JHACH Newsroom, Mar 2021

Getting the ‘Akt’ straight in angiogenesis, DDNews, Mar 2018

Angiogenesis - Latest research and news, Ivanhoe Broadcast, Feb 2018

Study sheds light on how the body forms new blood vessels, Futurism, Nov 2017

Top stories of 2017: #10) Scientists find key to regenerating blood vessels, EurekAlert!, Dec 2017

To treat breast cancer, give it a lifeline, SBP Beaker Blog, (October 2016)

Molecule that fixes “leaky” blood vessels can impact cancer, stroke, and blindness, SBP Beaker Blog, (March 2015)

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