Masanobu Komatsu, PhD

Dr. Komatsu is a senior Principal Investigator at the Cancer & Blood Disorders Institute and the Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital. He is an Associate Professor in the Department of Orthopaedic Surgery and Oncology and a member of Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine. 

He 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 post-doctoral studies under Erkki Ruoslahti, M.D., Ph.D., at the Sanford Burnham Prebys Medical Discovery Institute.

Dr. Komatsu became an assistant professor in the University of Alabama at Birmingham Department of Pathology while maintaining an adjunct position with Sanford Burnham. He joined Sanford Burnham full time in 2008 before coming to Johns Hopkins All Children’s in 2018. He holds patents related to the R-RAS protein and peptide-mediated vascular targeting of pulmonary arterial hypertension (PAH).

• New therapy kickstarts immune response to cancer. Interview by Baltimore Sun, Oct 2025
• Johns Hopkins Researchers Discover Innovative Immune System Enhancement to Combat Cancer Cells. Bioengineer, Sep 2025
• Scientists create tumor immune hubs to stop cancer growth and prevent relapse. Brighter side of news, Sep 2025
• 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

600, 5th street South
St. Petersburg, FL 33701

mkomats1@jhmi.edu

Tertiary lymphoid structures in cancer, Peptide-directed target-specific drug delivery, Normalization of pathologically remodeling/regenerating vasculature

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

1. Immuno-Oncology Program

Drug induction of tertiary lymphoid structures

Many malignant tumors are immune-suppressive or “immune cold”, which makes them unresponsive to cancer treatments. The goal of this research is to convert immune cold tumors “immune hot” or immune responsive so that patient’s defense mechanism will destroy cancer cells and enhance efficacy of conventional chemotherapy and immunotherapy. Dr. Komatsu’s team explores novel strategies to do this by activating key innate and adaptive immune pathways. Their current focus is ectopic lymphoid structures called tertiary lymphoid structures (TLS). The abundant TLS formation in patients’ tumors is strongly associated with therapy response and cancer survival. Dr. Komatsu’s research team has discovered that simultaneous activation of STING and lymphotoxin-β receptor pathways induces fully functional TLS in TLS-free tumors and provides protection against future recurrence and metastasis, enabling complete cure. Using this approach, functional TLS can be induced without any preconditioning, in different tumor types and anatomical sites, not restricted to certain organs such as the immune environment of the lung. The team demonstrated that “spicing up” the tumor immune environment with STING activation improves the “fitness” of TLS and dramatically enhances B cell and T cell responses against tumors. Dr. Komatsu’s team is further investigating the mechanism of action of TLS-based therapy and developing its clinical use in adult and pediatric cancer treatment.

2. Drug Targeting Program

Innovation in drug delivery

The other research program of Dr. Komatsu's laboratory is to develop and examine novel vascular targeting strategies for target-specific drug delivery guided by specific peptides. Peptide-directed vascular targeting takes advantage of unique molecular signatures of blood vessels at specific locations in the body. Originally developed by Dr. Erkki Ruoslahti, this technology enables the direct delivery of drugs to tumors or other diseased tissues through the vascular network. Since drugs are targeted to specific disease sites, it is possible to enhance drug efficacy while reducing the effective dose and minimizing adverse effects associated with standard chemotherapies. In collaboration with IF7Cure, Dr. Komatsu has been advancing the clinical development of IF7-SN38, an IF7 peptide-conjugated chemotherapeutic agent. IF7-SN38 is currently being evaluated in a veterinary clinical trial for pet dogs with cancer. Building on this work, the team is working with the U.S. Food and Drug Administration (FDA) toward an Investigational New Drug (IND) application to enable a Phase I clinical trial and the first-in-human evaluation of IF7-SN38.

3. Vascular Biology Program

Normalization of pathologically remodeled blood vessels

Malfunction and malformation of blood vessels are associated with a broad range of medical conditions, including cancer, cardiovascular diseases, and neurological disorders. The goal of this research is to find a way to reverse the process of abnormal vessel formation and restore normal function to these vessels. Normalization of blood vessels provides unique therapeutic opportunities. It can enhance the efficacy of cancer treatments and potentiate anti-tumor immunity, reestablish blood flow to ischemic hearts and limbs, and prevent blindness caused by diabetic retinopathy or macular degeneration. Dr. Komatsu's research team has identified a key role for the small GTPase R-Ras in promoting vessel maturation while preventing excessive angiogenic responses in regenerating vasculature. Unlike K-Ras or H-Ras, R-Ras inhibits vascular cell proliferation and invasion and promotes quiescence. The elevated R-Ras expression normalizes pathologically regenerating blood vessels. There is currently no successful therapeutic strategy for vascular normalization. Dr. Komatsu's team 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 unique activities of R-Ras make this Ras homolog an important subject of investigation in search of a new strategy for manipulating blood vessel function.

The overall mission of Dr. Komatsu’s research is to take a multidisciplinary approach to address important unmet medical needs in cancer and various other diseases. The broad research background of his team including cancer biology, immunology, and vascular biology allows them to bring multiple disciplines together to basic research, application, and technology development. The current research focus of the laboratory is twofold. One is to investigate the tumor immune landscape and tumor vasculature, and through this knowledge, develop novel strategies to remodel the tumor microenvironment for therapeutic advantage. In particular, the research team is focused on investigating tertiary lymphoid structures (TLS), lymph node-like structures of lymphocyte aggregates ectopically formed in tumors, and their roles in developing immunity against cancer cells. The other area of research is to develop novel vascular targeting strategies for the delivery of therapeutics and imaging probes to diseased organs and tissues.

• Simultaneous STING and lymphotoxin-β receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunity. Sawada J, Kikuchi Y, Duah M, Herrera JL, Kanamori F, Csomos K, Stansel T, Hiraoka N, Yoshida M, Walter J, Ware CF, and Komatsu M. Nature Immunology. 2025; 26(10):1766-1780. PMID: 40897896
• Akt3 activation by R-Ras in an endothelial cell enforces quiescence and barrier stability of neighboring endothelial cells via Jagged1. Herrera JL and Komatsu M. Cell Reports. 2024; 43(3):113837. PMID: 38402584
• Molecular signature of tumor-associated high endothelial venules that can predict breast cancer survival. Sawada J, Hiraoka N, Qi R, Jiang L, Fournier-Goss AE, Yoshida M, Kawashima H, Komatsu M. Cancer Immunology Research. 2022; 10(4):468-481. PMID: 35201289
• R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature. Li F, Sawada J, and Komatsu M. Nature Communications. 2017; 8(1):1720. PMID: 29170374
• Small GT Pase R-Ras regulates integrity and functionality of tumor blood vessels. Sawada J, Urakami T, Li F, Urakami A, Zhu W, Fukuda M, Li DY, Ruoslahti E, Komatsu M. Cancer Cell. 2012 Aug 14;22(2):235-49. PMID: 22897853

• R-Ras activity in vascular regulation, U.S. Patent No. US8506965 B2
• Compositions containing a pharmacophore with selectivity to diseased tissue and methods of making same, U.S. Patent No. US20190022170A1
• CAR Peptide for Homing, Diagnosis & Targeted Therapy for Pulmonary and Fibrotic Disorders, U.S. Patent No. US9180161 B2

• Altmetric Score 99th percentile and featured in 18 public news outlets. Simultaneous STING and lymphotoxin-β receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunity. Nature Immunology, 2025
• Top 10 most popular science news release of 2017
• Altmetric Score 98th percentile 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. Am J Pathol., 2011
• Article selected by the Faculty of 1000. R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nat Med, 2005
• Ruth L. Kirschstein National Research Service Award, NIH 5 T32 CA 09579, 2001-2002
• Winner, Sylvester Cancer Center Research Competition, 2000
• Third place, Sylvester Cancer Center Research Competition, 1999
• Winner, Sylvester Cancer Center Research Competition, University of Miami, 1998

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