|
Affiliation |
Graduate School of Engineering Science Department of Life Science Life Science Course |
FUJITA Kaori
|
|
|
Research Interests 【 display / non-display 】
-
cell biology
-
molecular biology
-
p53
-
p53 isoform
-
cellular senescence
Graduating School 【 display / non-display 】
-
1991.04-1995.03
Tohoku University Faculty of Pharmaceutical Science Graduated
Graduate School 【 display / non-display 】
-
1997.04-2000.03
Tohoku University Graduate School, Division of Pharmaceutical Sciences Doctor's Degree Program Completed
-
1995.04-1997.03
Tohoku University Graduate School, Division of Pharmaceutical Sciences Master's Degree Program Completed
Campus Career 【 display / non-display 】
-
2021.04-Now
Akita University Graduate School of Engineering Science Department of Life Science Life Science Course Lecturer
External Career 【 display / non-display 】
-
2010.01-2012.01
National Cancer Institute, National Institutes of Health, USA Laboratory of Human Carcinogenesis Federal Employee, Research Fellow
-
2005.02-2009.01
National Cancer Institute, National Institutes of Health, USA Laboratory of Human Carcinogenesis Visiting Fellow
Academic Society Affiliations 【 display / non-display 】
-
2019.12-Now
United Kingdom
International Cell Senescence Association (ICSA)
Research Areas 【 display / non-display 】
-
Life Science / Medical biochemistry
-
Life Science / Cell biology
-
Life Science / Orthopedics
-
Life Science / Pathological biochemistry
Research Achievements 【 display / non-display 】
-
p53 isoforms in cellular senescence- and ageing-associated biological and physiological functions.
Kaori FUJITA
International Journal of Molecular Sciences 20 ( 23 ) 6023 2019.11 [Refereed] [Invited]
Research paper (journal) Single author
-
Positive feedback between p53 and TRF2 during telomere-damage signaling and cellular senescence.
Kaori FUJITA, Izumi Horikawa, Abdul M Mondal, Lisa M Miller Jenkins, et al.
Nature Cell Biology 12 ( 12 ) 1205 - 1212 2010.12 [Refereed]
Research paper (journal) International Co-author
-
p53 isoforms Δ133p53 and p53β are endogenous regulators of replicative cellular senescence.
Kaori FUJITA, Abudal M Mondal, Izumi Horikawa, Giang H Nguyễn, et al.
Nature Cell Biology 11 ( 9 ) 1135 - 1142 2009.09 [Refereed]
Research paper (journal) International Co-author
-
Autophagic degradation of the inhibitory p53 isoform Δ133p53α as a regulatory mechanism for p53-mediated senescence.
Izumi Horikawa, Kaori FUJITA, Lisa M Miller Jenkins, Yukiharu Hiyoshi, et al.
Nature Communications 5 4706 2014.08 [Refereed]
Research paper (journal) International Co-author
-
p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes.
Abdul M Mondal, Izumi Horikawa, Sharon R Pine, Kaori FUJITA, et al.
International Journal of Clinical Investigation 123 ( 12 ) 5247 - 5257 2013.12 [Refereed]
Research paper (journal) International Co-author
-
Changes in acetyl-CoA mediate Sik3-induced maturation of chondrocytes in endochondral bone formation
Kosai A.
Biochemical and Biophysical Research Communications ( Biochemical and Biophysical Research Communications ) 516 ( 4 ) 1097 - 1102 2019.09 [Refereed]
Domestic Co-author
The maturation of chondrocytes is strictly regulated for proper endochondral bone formation. Although recent studies have revealed that intracellular metabolic processes regulate the proliferation and differentiation of cells, little is known about how changes in metabolite levels regulate chondrocyte maturation. To identify the metabolites which regulate chondrocyte maturation, we performed a metabolome analysis on chondrocytes of Sik3 knockout mice, in which chondrocyte maturation is delayed. Among the metabolites, acetyl-CoA was decreased in this model. Immunohistochemical analysis of the Sik3 knockout chondrocytes indicated that the expression levels of phospho-pyruvate dehydrogenase (phospho-Pdh), an inactivated form of Pdh, which is an enzyme that converts pyruvate to acetyl-CoA, and of Pdh kinase 4 (Pdk4), which phosphorylates Pdh, were increased. Inhibition of Pdh by treatment with CPI613 delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture. These results collectively suggest that decreasing the acetyl-CoA level is a cause and not result of the delayed chondrocyte maturation. Sik3 appears to increase the acetyl-CoA level by decreasing the expression level of Pdk4. Blocking ATP synthesis in the TCA cycle by treatment with rotenone also delayed chondrocyte maturation in metatarsal primordial cartilage in organ culture, suggesting the possibility that depriving acetyl-CoA as a substrate for the TCA cycle is responsible for the delayed maturation. Our finding of acetyl-CoA as a regulator of chondrocyte maturation could contribute to understanding the regulatory mechanisms controlling endochondral bone formation by metabolites.
-
骨代謝と病気の新たなクロストーク:臓器連関から創薬まで 疾患特異的ヒトiPS細胞を用いた成長板軟骨モデルの確立と創薬への応用
木村 武司, 尾崎 友則, 藤田 香里, 山下 晃弘, 森岡 美穂, 大薗 恵一, 妻木 範行
日本骨代謝学会学術集会プログラム抄録集 ( (一社)日本骨代謝学会 ) 36回 115 - 115 2018.07
-
Horikawa I.
Cell Death and Differentiation ( Cell Death and Differentiation ) 24 ( 6 ) 1017 - 1028 2017.06
p53 functions to induce cellular senescence, which is incompatible with self-renewal of pluripotent stem cells such as induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC). However, p53 also has essential roles in these cells through DNA damage repair for maintaining genomic integrity and high sensitivity to apoptosis for eliminating severely damaged cells. We hypothesized that Delta 133p53, a physiological inhibitory p53 isoform, is involved in the balanced regulation of self-renewing capacity, DNA damage repair and apoptosis. We examined 12 lines of human iPSC and their original fibroblasts, as well as three ESC lines, for endogenous protein levels of Delta 133p53 and full-length p53 (FL-p53), and mRNA levels of various p53 target genes. While FL-p53 levels in iPSC and ESC widely ranged from below to above those in the fibroblasts, all iPSC and ESC lines expressed elevated levels of Delta 133p53. The p53-inducible genes that mediate cellular senescence (p21(WAF1), miR-34a, PAI-1 and IGFBP7), but not those for apoptosis (BAX and PUMA) and DNA damage repair (p53R2), were downregulated in iPSC and ESC. Consistent with these endogenous expression profiles, overexpression of Delta 133p53 in human fibroblasts preferentially repressed the p53-inducible senescence mediators and significantly enhanced their reprogramming to iPSC. The iPSC lines derived from Delta 133p53 overexpressing fibroblasts formed well-differentiated, benign teratomas in immunodeficient mice and had fewer numbers of somatic mutations than an iPSC derived from p53-knocked-down fibroblasts, suggesting that Delta 133p53 overexpression is non-or less oncogenic and mutagenic than total inhibition of p53 activities. Overexpressed Delta 133p53 prevented FL-p53 from binding to the regulatory regions of p21(WAF1) and miR-34a promoters, providing a mechanistic basis for its dominant-negative inhibition of a subset of p53 target genes. This study supports the hypothesis that upregulation of Delta 133p53 is an endogenous mechanism that facilitates human somatic cells to become self-renewing pluripotent stem cells with maintained apoptotic and DNA repair activities.
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
-
Grant-in-Aid for Scientific Research(C)
Project Year： 2023.04 - 2026.03
-
Grant-in-Aid for Scientific Research(B)
Project Year： 2018.04 - 2021.03
-
Grant-in-Aid for Challenging Research (Pioneering)/(Exploratory)
Project Year： 2014.04 - 2016.03
-
Grant-in-Aid for Scientific Research(B)
Project Year： 2013.04 - 2017.03