Keigi Fujiwara, PhD
Department of Cardiology, Division of Internal Medicine
About Dr. Fujiwara
I received my PhD in Biology from the University of Pennsylvania and postdoctoral training at the Department of Cell Biology and Anatomy at Harvard Medical School under Dr. Thomas Pollard. After my postdoctoral training, I was appointed an Assistant Professor and then Associate Professor. I helped create the Department of Structural Analysis with the newly founded National Cardiovascular Center Research Institute in Japan. I served as chairman of the department for 16 years. Afterwards, I returned to the US as a Professor in the Department of Medicine at Rochester University Medical School. In 2014, I joined MD Anderson as a Professor in the Department of Cardiology.
Present Title & Affiliation
Primary Appointment
Professor, Department of Cardiology - Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
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. While many investigators are studying various responses, such as changes in the gene and protein expression, morphological changes, activation of signaling cascades, and so on, of cells exposed to mechanical forces, we focus onto mechanosensing. How do cells sense 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, endothelial dysfunction, and cancer treatment-induced cardiovascular events. These latter studies are conducted in collaboration with Dr. Jun-ichi Abe, Professor, UT MD Anderson Cancer Center. In addition, we are investigating how to mitigate effects of space radiation and microgravity which are known risk factors for astronauts to develop cancer and other diseases including neurological, cardiovascular and general systemic dysfunction. 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 using confocal and multi-photon microscopy, FRET, TIRF, intravital microscopy, polarization microscopy, and time lapse recording. More recently, we employ Imaging Mass Cytometry (IMC) to study expression of >30 proteins simultaneously within cells in tissues.
Education & Training
Degree-Granting Education
| 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 |
Postgraduate Training
| 1974-1977 | Research Fellowship, Harvard Medical School, Department of Anatomy, Boston, MA |
| 1973-1973 | Physiology Course, Marine Biological Laboratory, Wood Holes, MA |
Experience & Service
Academic Appointments
Research Professor, Department of Department of Medicine, Division of Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, 2007 - 2014
Research Professor, Department of Department of Biomedical Engineering, Division of School of Engineering, University of Rochester, Rochester, NY, 2007 - 2014
Professor, Department of Department of Biomedical Engineering, Division of School of Engineering, University of Rochester, Rochester, NY, 2006 - 2007
Professor, Department of Department of Medicine, Division of Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, 2001 - 2007
Administrative Appointments/Responsibilities
Co-Director, Department of Department of Medicine, University of Rochester, Rochester, NY, 2013 - 2014
Director, Department of Aab Cardiovascular Research Institute, University of Rochester, Rochester, NY, 2005 - 2014
Other Appointments/Responsibilities
Microscopy Core Committee Member, University of Rochester, Rochester, NY, 2010 - 2014
Annotator, The Cell: An Imaging Library, American Society for Cell Biology, Bethesda, MD, 2010 - 2012
Electron Microscope Core Committee Member, University of Rochester, Rochester, NY, 2006 - 2014
Honors & Awards
| 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) |
Selected Publications
Peer-Reviewed Articles
- Yamanouchi S, Rhone J, Mao JH, Fujiwara K, Saganti PB, Takahashi A, Hada M. Simultaneous Exposure of Cultured Human Lymphoblastic Cells to Simulated Microgravity and Radiation Increases Chromosome Aberrations. Life (Basel) 10(9), 2020. e-Pub 2020. PMID: 32927618.
- McBeath E, Parker-Thornburg J, Fujii Y, Aryal N, Smith C, Hofmann MC, Abe JI, Fujiwara K. Rapid Evaluation of CRISPR Guides and Donors for Engineering Mice. Genes (Basel) 11(6), 2020. e-Pub 2020. PMID: 32521708.
- Luo W, Wang Y, Zhang L, Ren P, Zhang C, Li Y, Azares AR, Zhang M, Guo J, Ghaghada KB, Starosolski ZA, Rajapakshe K, Coarfa C, Li Y, Chen R, Fujiwara K, Abe JI, Coselli JS, Milewicz DM, LeMaire SA, Shen YH. Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture. Circulation 141(1):42-66, 2020. e-Pub 2019. PMID: 31887080.
- Kotla S, Le NT, Vu HT, Ko KA, Gi YJ, Thomas TN, Giancursio C, Lusis AJ, Cooke JP, Fujiwara K, Abe JI. Endothelial senescence-associated secretory phenotype (SASP) is regulated by Makorin-1 ubiquitin E3 ligase. Metabolism 100:153962, 2019. e-Pub 2019. PMID: 31476350.
- Kotla S, Vu HT, Ko KA, Wang Y, Imanishi M, Heo KS, Fujii Y, Thomas TN, Gi YJ, Mazhar H, Paez-Mayorga J, Shin JH, Tao Y, Giancursio CJ, Medina JL, Taunton J, Lusis AJ, Cooke JP, Fujiwara K, Le NT, Abe JI. Endothelial senescence is induced by phosphorylation and nuclear export of telomeric repeat binding factor 2-interacting protein. JCI Insight 4(9), 2019. e-Pub 2019. PMID: 31045573.
- Abe JI, Ko KA, Kotla S, Wang Y, Paez-Mayorga J, Shin IJ, Imanishi M, Vu HT, Tao Y, Leiva-Juarez MM, Thomas TN, Medina JL, Won JH, Fujii Y, Giancursio CJ, McBeath E, Shin JH, Guzman L, Abe RJ, Taunton J, Mochizuki N, Faubion W, Cooke JP, Fujiwara K, Evans SE, Le NT. MAGI1 as a link between endothelial activation and ER stress drives atherosclerosis. JCI Insight 4(7), 2019. e-Pub 2019. PMID: 30944250.
- Moslehi J, Fujiwara K, Guzik T. Cardio-oncology: a novel platform for basic and translational cardiovascular investigation driven by clinical need. Cardiovasc Res 115(5):819-823, 2019. PMID: 30888396.
- Singh MV, Kotla S, Le NT, Ae Ko K, Heo KS, Wang Y, Fujii Y, Thi Vu H, McBeath E, Thomas TN, Jin Gi Y, Tao Y, Medina JL, Taunton J, Carson N, Dogra V, Doyley MM, Tyrell A, Lu W, Qiu X, Stirpe NE, Gates KJ, Hurley C, Fujiwara K, Maggirwar SB, Schifitto G, Abe JI. Senescent Phenotype Induced by p90RSK-NRF2 Signaling Sensitizes Monocytes and Macrophages to Oxidative Stress in HIV-Positive Individuals. Circulation 139(9):1199-1216, 2019. PMID: 30586719.
- Hada M, Ikeda H, Rhone JR, Beitman AJ, Plante I, Souda H, Yoshida Y, Held KD, Fujiwara K, Saganti PB, Takahashi A. Increased Chromosome Aberrations in Cells Exposed Simultaneously to Simulated Microgravity and Radiation. Int J Mol Sci 20(1), 2018. e-Pub 2018. PMID: 30583489.
- Le NT, Martin JF, Fujiwara K, Abe JI. Sub-cellular localization specific SUMOylation in the heart. Biochim Biophys Acta Mol Basis Dis 1863(8):2041-2055, 2017. e-Pub 2017. PMID: 28130202.
- Snyder JL, McBeath E, Thomas TN, Chiu YJ, Clark RL, Fujiwara K. Mechanotransduction properties of the cytoplasmic tail of PECAM-1. Biol Cell 109(8):312-321, 2017. e-Pub 2017. PMID: 28643869.
- Lin SC, Lee YC, Yu G, Cheng CJ, Zhou X, Chu K, Murshed M, Le NT, Baseler L, Abe JI, Fujiwara K, deCrombrugghe B, Logothetis CJ, Gallick GE, Yu-Lee LY, Maity SN, Lin SH. Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer. Dev Cell 41(5):467-480.e3, 2017. PMID: 28586644.
- Le NT, Sandhu UG, Quintana-Quezada RA, Hoang NM, Fujiwara K, Abe JI. Flow signaling and atherosclerosis. Cell Mol Life Sci 74(10):1835-1858, 2017. e-Pub 2016. PMID: 28039525.
- Mao Y, Luo W, Zhang L, Wu W, Yuan L, Xu H, Song J, Fujiwara K, Abe JI, LeMaire SA, Wang XL, Shen YH. STING-IRF3 Triggers Endothelial Inflammation in Response to Free Fatty Acid-Induced Mitochondrial Damage in Diet-Induced Obesity. Arterioscler Thromb Vasc Biol 37(5):920-929, 2017. e-Pub 2017. PMID: 28302626.
- Abe JI, Sandhu UG, Hoang NM, Thangam M, Quintana-Quezada RA, Fujiwara K, Le NT. Coordination of Cellular Localization-Dependent Effects of Sumoylation in Regulating Cardiovascular and Neurological Diseases. Adv Exp Med Biol 963:337-358, 2017. PMID: 28197922.
- Fujiwara K, Sheu SS. Mitochondrial dynamics regulate neointima formation. Cardiovasc Res 106(2):175-7, 2015. e-Pub 2015. PMID: 25800033.
- 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.
- 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.
Invited Articles
- Ko KA, Fujiwara K, Krishnan S, Abe JI. En face preparation of mouse blood vessels. J Vis Exp(123), 2017. e-Pub 2017. PMID: 28570508.
- 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.
- Chatterjee S, Fujiwara K, Pérez 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(12):H1451–H1462, 2015. e-Pub 2015. PMID: 25862828.
- 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.
- 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.
Grant & Contract Support
| Title: | Mechanism of PECAM-1 tyrosine phosphorylation |
| Funding Source: | American Heart Association |
| Role: | Principal Investigator |
| Title: | Fluid shear stress signal transduction in endothelium |
| Funding Source: | NIH/NHLBI |
| Role: | Co-Principal Investigator |
| Title: | Single molecule force spectroscopy analysis of PECAM-1 mechanotransduction |
| Funding Source: | NIH/NHLBI |
| Role: | Co-Principal Investigator |
| Title: | Implantable cell-embedded biosensor for heart failure |
| Funding Source: | Clinical Translational Science Institute (CTSI) Grant |
| Role: | Co-Principal Investigator |