Professor, Department of Cardiology - Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
I am a cell biologist interested in cell motility such as cell migration, cell division, intracellular organelle trafficking, and cell contraction. Our studies on the cytoskeleton of endothelial cells have led us to the field of endothelial mechanotransduction. Unique flow and cell stretch apparatuses are developed to study endothelial cell responses to mechanical forces. Through a series of in vitro cell and molecular biological studies, we were able to identify platelet endothelial cell adhesion molecule 1 (PECAM-1/CD31) to be a mechanosensor molecule of endothelial cells. The precise mechanism for mechanotransduction by PECAM-1 is being investigated. Our studies are also aimed at endothelial cell biology and physiology, especially on topics related to the cytoskeleton and cell adhesion and to cell signaling in the context of atherogenesis and endothelial dysfunction. In the past several years, I am collaborating with Dr. Jun-ichi Abe, Professor, UT MD Anderson Cancer Center, to study signaling cascades in endothelial cells that are exposed to disturbed flow. Identifying signaling cascades activated specifically by disturbed flow is an important step towards the discovery of new pharmacologic interventions for atherosclerosis and other cardiovascular diseases. Our studies are also focused on negative effects of cancer treatments on the cardiovascular system, which has become a critical issue for cancer patients and survivors. As a graduate student in the Biophysical Cytology Program at Penn headed by Dr. Shinya Inoue, I received arguably the best training on light microscopy. Throughout my scientific career, I have given numerous numbers of workshops, courses, and lectures on microscopy, especially fluorescence microscopy and live cell imaging techniques such as confocal and multi-photon microscopy, FRET, TIRF, intravital microscopy, polarization microscopy, and time lapse recording.
|1974||University of Pennsylvania, Phildelphia, PA, USA, PHD, Biology, Program in Biophysical Cytology|
|1968||International Christian University, Mitaka, JPN, BA, Natural Sciences; Division of Biology|
|1974-1977||Research Fellowship, Harvard Medical School, Department of Anatomy, Boston, MA|
|1973-1973||Physiology Course, Marine Biological Laboratory, Wood Holes, MA|
|1978||Steps-Toward-Independence Fellowship, Marine Biological Laboratory|
|1975||Muscular Dystrophy Association Postdoctoral Fellowship, Muscular Dystrophy Association|
|1962||American Field Service (AFS) International Scholarship, American Field Service (AFS)|
- Smolock EM, Burke RM, Wang C, Thomas T, Batchu SN, Qiu X, Zettel M, Fujiwara K, Berk BC, Korshunov VA. Intima modifier locus 2 controls endothelial cell activation and vascular permeability. Physiol Genomics 46(17):624-33, 2014. e-Pub 2014. PMID: 24986958.
- Heo KS, Cushman HJ, Akaike M, Woo CH, Wang X, Qiu X, Fujiwara K, Abe J. ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis. Circulation 130(2):180-91, 2014. e-Pub 2014. PMID: 25001623.
- Heo KS, Chang E, Le NT, Cushman H, Yeh ET, Fujiwara K, Abe J. De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis. Circ Res 112(6):911-23, 2013. e-Pub 2013. PMID: 23381569.
- Heo KS, Chang E, Takei Y, Le NT, Woo CH, Sullivan MA, Morrell C, Fujiwara K, Abe J. Phosphorylation of protein inhibitor of activated STAT1 (PIAS1) by MAPK-activated protein kinase-2 inhibits endothelial inflammation via increasing both PIAS1 transrepression and SUMO E3 ligase activity. Arterioscler Thromb Vasc Biol 33(2):321-9, 2013. e-Pub 2012. PMID: 23202365.
- Le NT, Heo KS, Takei Y, Lee H, Woo CH, Chang E, McClain C, Hurley C, Wang X, Li F, Xu H, Morrell C, Sullivan MA, Cohen MS, Serafimova IM, Taunton J, Fujiwara K, Abe J. A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis. Circulation 127(4):486-99, 2013. e-Pub 2012. PMID: 23243209.
- Kim GY, Nigro P, Fujiwara K, Abe J, Berk BC. p62 binding to protein kinase C ζ regulates tumor necrosis factor α-induced apoptotic pathway in endothelial cells. Arterioscler Thromb Vasc Biol 32(12):2974-80, 2012. e-Pub 2012. PMID: 23023376.
- Le NT, Takei Y, Shishido T, Woo CH, Chang E, Heo KS, Lee H, Lu Y, Morrell C, Oikawa M, McClain C, Wang X, Tournier C, Molina CA, Taunton J, Yan C, Fujiwara K, Patterson C, Yang J, Abe J. p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction. Circ Res 110(4):536-50, 2012. e-Pub 2012. PMID: 22267842.
- Wang XQ, Nigro P, World C, Fujiwara K, Yan C, Berk BC. Thioredoxin interacting protein promotes endothelial cell inflammation in response to disturbed flow by increasing leukocyte adhesion and repressing Kruppel-like factor 2. Circ Res 110(4):560-8, 2012. e-Pub 2012. PMID: 22267843.
- Miller CL, Cai Y, Oikawa M, Thomas T, Dostmann WR, Zaccolo M, Fujiwara K, Yan C. Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart. Basic Res Cardiol 106(6):1023-39, 2011. e-Pub 2011. PMID: 22012077.
- Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo CH, Abe J. PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol 193(5):867-84, 2011. PMID: 21624955.
- Chang E, Heo KS, Woo CH, Lee H, Le NT, Thomas TN, Fujiwara K, Abe J. MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation. Blood 117(8):2527-37, 2011. e-Pub 2010. PMID: 21131586.
- Nigro P, Abe J, Woo CH, Satoh K, McClain C, O'Dell MR, Lee H, Lim JH, Li JD, Heo KS, Fujiwara K, Berk BC. PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5. Blood 116(11):1971-9, 2010. e-Pub 2010. PMID: 20538799.
- Shi F, Harman J, Fujiwara K, Sottile J. Collagen I matrix turnover is regulated by fibronectin polymerization. Am J Physiol Cell Physiol 298(5):C1265-75, 2010. e-Pub 2010. PMID: 20107040.
- Chiu YJ, McBeath E, Fujiwara K. Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation. J Cell Biol 182(4):753-63, 2008. e-Pub 2008. PMID: 18710921.
- Kusano K, Thomas TN, Fujiwara K. Phosphorylation and localization of protein-zero related (PZR) in cultured endothelial cells. Endothelium 15(3):127-36, 2008. PMID: 18568953.
- Shi F, Chiu YJ, Cho Y, Bullard TA, Sokabe M, Fujiwara K. Down-regulation of ERK but not MEK phosphorylation in cultured endothelial cells by repeated changes in cyclic stretch. Cardiovasc Res 73(4):813-22, 2007. e-Pub 2006. PMID: 17289004.
- van Nieuw Amerongen GP, Natarajan K, Yin G, Hoefen RJ, Osawa M, Haendeler J, Ridley AJ, Fujiwara K, van Hinsbergh VW, Berk BC. GIT1 mediates thrombin signaling in endothelial cells: role in turnover of RhoA-type focal adhesions. Circ Res 94(8):1041-9, 2004. e-Pub 2004. PMID: 15016733.
- Osawa M, Masuda M, Kusano K, Fujiwara K. Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction: is it a mechanoresponsive molecule?. J Cell Biol 158(4):773-85, 2002. e-Pub 2002. PMID: 12177047.
- Hosokawa H, Ninomiya H, Kitamura Y, Fujiwara K, Masaki T. Vascular endothelial cells that express dystroglycan are involved in angiogenesis. J Cell Sci 115(Pt 7):1487-96, 2002. PMID: 11896196.
- Katoh K, Kano Y, Amano M, Kaibuchi K, Fujiwara K. Stress fiber organization regulated by MLCK and Rho-kinase in cultured human fibroblasts. Am J Physiol Cell Physiol 280(6):C1669-79, 2001. PMID: 11350763.
- Katoh K, Kano Y, Amano M, Onishi H, Kaibuchi K, Fujiwara K. Rho-kinase--mediated contraction of isolated stress fibers. J Cell Biol 153(3):569-84, 2001. PMID: 11331307.
- Konishi K, Kojima Si , Katoh T, Yazawa M, Kato K, Fujiwara K, Onishi H. Two new modes of smooth muscle myosin regulation by the interaction between the two regulatory light chains, and by the S2 domain. J Biochem 129(3):365-72, 2001. PMID: 11226875.
- Kojima S, Konishi K, Katoh K, Fujiwara K, Martinez HM, Morales MF, Onishi H. Functional roles of ionic and hydrophobic surface loops in smooth muscle myosin: their interactions with actin. Biochemistry 40(3):657-64, 2001. PMID: 11170382.
- Onishi H, Konishi K, Fujiwara K, Hayakawa K, Tanokura M, Martinez HM, Morales MF. On the tryptophan residue of smooth muscle myosin that responds to binding of nucleotide. Proc Natl Acad Sci U S A 97(21):11203-8, 2000. PMID: 11016961.
- Kano Y, Katoh K, Fujiwara K. Lateral zone of cell-cell adhesion as the major fluid shear stress-related signal transduction site. Circ Res 86(4):425-33, 2000. PMID: 10700447.
- Le NT, Takei Y, Izawa-Ishizawa Y, Heo K-S, Lee H, Smrcka AV, Miller BL, Ko KA, Ture S, Morrell C, Fujiwara K, Akaike M, Abe J. Identification of activators of ERK5 transcriptional activity by high-throughput screening and the role of endothelial ERK5 in vasoprotective effects induced by statins and antimalarial agents. J Immunol 193:3803-3815. e-Pub 2014.
- Xu S, Ha CH, Wang W, Xu X, Yin M, Jin FQ, Mastrangelo M, Koroleva M, Fujiwara K, Jin ZG.. PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling. Cellular Signaling 28:117-124, 2016.
- Heo KS, Le NT, Cushman HJ, Giancursio CJ, Chang E, Woo CH, Sullivan MA, Taunton J, Yeh ETH, Fujiwara K, Abe J.. Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function. J Clin Invest 125(3):1299-1310, 2015.
- Chatterjee S, Fujiwara K, Perez NG, Ushio-Fukai M, Fisher AB.. Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses. Am J Physiol Heart Circ Physiol 308:H1451–H1462, 2015.
- Mao Y, Luo W, Zhang L, Wu W, Yuan L, Xu H, Fujiwara K, Abe J, Wang XL, and Shen YH.. STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage. Arterioscler Thromb Vasc Biol.
- KO KA, Fujiwara K, Abe J.. En face preparation of mouse blood vessels. J Vis Exp.
|Title:||Mechanism of PECAM-1 tyrosine phosphorylation|
|Funding Source:||American Heart Association|
|Title:||Fluid shear stress signal transduction in endothelium|
|Title:||Single molecule force spectroscopy analysis of PECAM-1 mechanotransduction|
|Title:||Implantable cell-embedded biosensor for heart failure|
|Funding Source:||Clinical Translational Science Institute (CTSI) Grant|