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MASANOBU KOMATSU, PH.D.
Associate Professor

Primary Appointment:
Tumor Microenvironment

Secondary Appointment:
Cardiovascular Pathobiology

858.646.3100 x4502 (phone)
mkomatsu@sanfordburnham.org

RESEARCH FOCUS, BIOGRAPHY, STAFF, PUBLICATIONS

Research Focus
Malfunction of blood vessels and abnormal vessel growth are associated with many medical conditions, ranging from heart diseases and cancer, to metabolic problems such as diabetes and to age-related conditions such as macular degeneration. Dr. Komatsu’s research goal is to find a way to reverse the process of abnormal vessel regeneration and restore normal functions into these vessels. The improvement of vessel functionality will enhance drug delivery and radiation efficacy during cancer treatment, avoid occlusions of coronary arteries, and slow the deterioration of the eyesight in elderly people. Dr. Komatsu’s current research focuses on the role of an intracellular signaling protein, R-Ras, in inhibiting the abnormal vessel growth and normalizing the disease-associated defective vasculature.

During development and normal regeneration of adult tissues, newly formed blood vessels undergo maturation process. It is important to understand the cellular and molecular basis of this process because its failure will lead to structural and functional deficiencies of the blood vessels, which are typically seen in pathological lesions such as tumors. Dr. Komatsu’s recent studies indicate that R-Ras is one of the key promoters of blood vessel maturation during vascular remodeling and regeneration. R-Ras promotes this important biological process through regulating vascular smooth muscle cells, endothelial cells, and pericytes (mural cells), which are all essential cellular constituents of the blood vessel wall. These findings suggest that R-Ras signaling may also be useful in tissue engineering and therapeutic angiogenesis where formation of ‘functional’ vessels is crucial.


Biography
Dr. Komatsu earned his undergraduate degree and his Ph.D. at the University of Miami, where he also completed post-doctoral studies in immunology. He continued his post-doctoral studies at Sanford-Burnham, as a fellow in the lab of Dr. Erkki Ruoslahti, Sanford-Burnham’s president (1989-2002). After five years at Sanford-Burnham, Dr. Komatsu became an Assistant Professor in the Department of Pathology, Division of Molecular and Cellular Pathology at the University of Alabama at Birmingham and maintained an adjunct faculty and investigator status with the Sanford-Burnham Cancer Center in La Jolla. In 2008, Dr. Komatsu joined Sanford-Burnham full-time with a primary appointment to the Tumor Microenvironment program in the Cancer Center and with a secondary appointment to the Cardiovascular Pathobiology program in the Diabetes and Obesity Research Center.

Dr. Komatsu holds a patent in R-Ras Activity in Vascular Regulation along with inventors: David Mann and Erkki Ruoslahti, 2007.


Selected Publications

  1. Xu, L. and Komatsu, M. (2009). Promoter cloning and characterization of the anti-vascular proliferation gene, R-ras: Role of ETS and Sp binding motifs. J Biol Chem 284: 2706-2718.
  2. Pilch, J., Brown, D. M., Komatsu, M., Jarvinen, T. A., Yang, M., Peters, D., Hoffman, R. M., and Ruoslahti, E. (2006). Peptides selected for binding to clotted plasma accumulate in tumor stroma and wounds. Proc Natl Acad Sci USA 103: 2800-2804.
  3. Komatsu, M. and Ruoslahti, E. R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. (2005). Nat Med 11, 1346-1350.
  4. Jan, Y., Matter, M, Pai, J., Chen. Y., Pilch, J., Komatsu, M., Ong, E., Fukuda, M., Ruoslahti, E. (2004). A Mitochondrial Protein, Bit1, Mediates Apoptosis Regulated by Integrins and Groucho/TLE Co-Repressors. Cell 116, 751-762.
  5. Komatsu, M., Mammolenti, M., Jones, M., Jurecic, R., Sayers, T. J., and Levy, R. B. (2003). Antigen-primed CD8+ T cells can mediate resistance, preventing allogeneic marrow engraftment in the simultaneous absence of perforin-, CD95L-, TNFR1-, and TRAIL-dependent killing. Blood 101, 3991-3999.
  6. Komatsu, M., Arango, M. E., and Carraway, K. L. (2002). Synthesis and secretion of Muc4/sialomucin complex: implication of intracellular proteolysis. Biochem J 368, 41-48.
  7. Jepson, S.*, Komatsu, M.*, Haq, B., Arango, M. E., Huang, D., Carraway, C. A., and Carraway, K. L. (2002). Muc4/sialomucin complex, the intramembrane ErbB2 ligand, induces specific phosphorylation of ErbB2 and enhances expression of p27(kip), but does not activate mitogen-activated kinase or protein kinaseB/Akt pathways. Oncogene 21, 7524-7532.
  8. Komatsu, M., Jepson, S., Arango, M. E., Carothers Carraway, C. A., and Carraway, K. L. (2001). Muc4/sialomucin complex, an intramembrane modulator of ErbB2/HER2/Neu, potentiates primary tumor growth and suppresses apoptosis in a xenotransplanted tumor. Oncogene 20, 461-470.