Tomoo Iwakuma, MD, PhD
Title | Professor and Director, Translational Laboratory Oncology Research |
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Institution | Children's Mercy Kansas City |
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Department | Pediatrics |
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Address | 2401 Gillham Rd Kansas City MO 64108
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ORCID
![ORCID Icon](https://researchers.childrensmercy.org/Framework/Images/orcid_16x16(1).gif) | 0000-0001-7249-7958 ![Additional info](https://researchers.childrensmercy.org/Framework/Images/info.png) |
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vCard | Download vCard |
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Title | Professor of Pediatrics |
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Institution | University of Missouri-Kansas City |
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Department | Pediatrics |
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Title | Research Professor of Cancer Biology |
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Institution | University of Kansas Medical Center |
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Department | Biology |
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Biography Kyushu University, Fukuoka, Japan | MD, PhD | 1997 | Molecular biology | Kyushu University, Fukuoka, Japan | Residency | 1993 | Orthopedics | Baylor College of Medicine, Houston, TX | Post Doctorial | 2000 | Pharmacology | MD Anderson Cancer Center, Houston | Instructor | 2005 | Molecular genetics |
2015 | Mentorship Award, University of Kansas School of Medicine | 2021 - 2021 | KUCC Director's Award - Basic Science, Children's Mercy Research Institute |
Overview Research Dr. Iwakuma's primary research focuses on the field of Cancer Research, especially dissecting the mechanism of cancer progression and discovering novel drugs or compounds that specifically kill cancer cells, with special focus on the tumor suppressor p53 pathway.
R01CA174735 (IWAKUMA, TOMOO)May 1, 2014 - Apr 30, 2020 NIH The role of MDM2-MTBP axis in cancer metastasis Role: Principal Investigator |
| R01CA214916 (IWAKUMA, TOMOO)Mar 9, 2018 - Feb 28, 2024 NIH Control of mutant p53 stability via the mevalonate pathway-DNAJA1 axis Role: Principal Investigator |
| R13CA281369 (IWAKUMA, TOMOO)Sep 15, 2023 - Aug 31, 2024 NIH The 10th International MDM2 Workshop Role: Principal Investigator |
Bibliography
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Ohki R, Itahana K, Iwakuma T. . Genes to Cells. "The 10th International MDM2 Workshop"—Opening Up New Avenues for MDM2 and p53 Research, the first International MDM2 Workshop in Asia. 2024.
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Ohki R, Itahana K, Iwakuma T. "The 10th International MDM2 Workshop": Opening up new avenues for MDM2 and p53 research, the First International MDM2 Workshop in Asia. Genes Cells. 2024 Mar 29. PMID: 38553254.
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Kamath D, Iwakuma T, Bossmann SH. Therapeutic potential of combating cancer by restoring wild-type p53 through mRNA nanodelivery. Nanomedicine. 2024 Feb; 56:102732. PMID: 38199451.
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Wang ZH, Li J, Liu Q, Qian JC, Li QQ, Wang QY, Zeng LT, Li SJ, Gao X, Pan JX, Gao XF, Wu K, Hu GX, Iwakuma T, Cai JP. A modified nucleoside O6-methyl-2'-deoxyguanosine-5'-triphosphate exhibits anti-glioblastoma activity in a caspase-independent manner. Pharmacol Res. 2024 Jan; 199:106990. PMID: 37984506.
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Wang QY, Zhang W, Zhao Y, Chen HL, Liu Q, Wang ZH, Zeng LT, Li J, Chen SJ, Wei L, Iwakuma T, Cai JP. Colonic L-cell impairment in aged subjects with type 2 diabetes leads to diminished GLP-1 production. Diabetes Metab Syndr. 2023 Dec; 17(12):102907. PMID: 37980723.
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Ranjan A, Thoenen EA, Kaida A, Wood S, Van Dyke T, Iwakuma T. Characterization of an Mtbp Hypomorphic Allele in a Diethylnitrosamine-Induced Liver Carcinogenesis Model. Cancers (Basel). 2023 Sep 16; 15(18). PMID: 37760565.
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Gonzalez E, Ahmed AA, McCarthy L, Chastain K, Habeebu S, Zapata-Tarres M, Cardenas-Cardos R, Velasco-Hidalgo L, Corcuera-Delgado C, Rodriguez-Jurado R, Garc?a-Rodr?guez L, Parrales A, Iwakuma T, Farooqi MS, Lee B, Weir SJ, Flatt TG. Perinucleolar Compartment (PNC) Prevalence as an Independent Prognostic Factor in Pediatric Ewing Sarcoma: A Multi-Institutional Study. Cancers (Basel). 2023 Apr 10; 15(8). PMID: 37190159.
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Li J, Zhang H, Wang ZH, Li YX, Zhang LQ, Cui J, Li DN, Wang ZH, Liu Q, Liu Z, Iwakuma T, Cai JP. 8-oxo-dGTP curbs tumor development via S phase arrest and AIF-mediated apoptosis. Free Radic Biol Med. 2023 02 20; 196:53-64. PMID: 36640852.
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Nishikawa S, Iwakuma T. Drugs Targeting p53 Mutations with FDA Approval and in Clinical Trials. Cancers (Basel). 2023 Jan 09; 15(2). PMID: 36672377.
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Nishikawa S, Kaida A, Parrales A, Ranjan A, Alalem M, Ren H, Schoenen FJ, Johnson DK, Iwakuma T. DNAJA1- and conformational mutant p53-dependent inhibition of cancer cell migration by a novel compound identified through a virtual screen. Cell Death Discov. 2022 Oct 31; 8(1):437. PMID: 36316326.
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Alalem M, Bhosale M, Ranjan A, Yamamoto S, Kaida A, Nishikawa S, Parrales A, Farooki S, Anant S, Padhye S, Iwakuma T. Mutant p53 Depletion by Novel Inhibitors for HSP40/J-Domain Proteins Derived from the Natural Compound Plumbagin. Cancers (Basel). 2022 Aug 29; 14(17). PMID: 36077724.
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Kaida A, Iwakuma T. Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members. Int J Mol Sci. 2021 Dec 16; 22(24). PMID: 34948322.
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Kaida A, Yamamoto S, Parrales A, Young ED, Ranjan A, Alalem MA, Morita KI, Oikawa Y, Harada H, Ikeda T, Thomas SM, Diaz FJ, Iwakuma T. DNAJA1 promotes cancer metastasis through interaction with mutant p53. Oncogene. 2021 08; 40(31):5013-5025. PMID: 34183772.
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Liang Y, Lyon RC, Pellman J, Bradford WH, Lange S, Bogomolovas J, Dalton ND, Gu Y, Bobar M, Lee MH, Iwakuma T, Nigam V, Asimaki A, Scheinman M, Peterson KL, Sheikh F. Desmosomal COP9 regulates proteome degradation in arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Clin Invest. 2021 06 01; 131(11). PMID: 33857019.
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Ghosh M, Saha S, Bettke J, Nagar R, Parrales A, Iwakuma T, van der Velden AWM, Martinez LA. Mutant p53 suppresses innate immune signaling to promote tumorigenesis. Cancer Cell. 2021 04 12; 39(4):494-508.e5. PMID: 33545063.
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Young ED, Manley SJ, Beadnell TC, Shearin AE, Sasaki K, Zimmerman R, Kauffman E, Vivian CJ, Parasuram A, Iwakuma T, Grandgenett PM, Hollingsworth MA, O'Neil M, Welch DR. Suppression of pancreatic cancer liver metastasis by secretion-deficient ITIH5. Br J Cancer. 2021 01; 124(1):166-175. PMID: 33024269.
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Parrales A, Iwakuma T. TAp63-miRNA-AURKA Axis as a Therapeutic Target for Cutaneous Squamous Cell Carcinoma. Cancer Res. 2020 06 15; 80(12):2439-2440. PMID: 32540854.
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Subramaniam D, Angulo P, Ponnurangam S, Dandawate P, Ramamoorthy P, Srinivasan P, Iwakuma T, Weir SJ, Chastain K, Anant S. Suppressing STAT5 signaling affects osteosarcoma growth and stemness. Cell Death Dis. 2020 02 24; 11(2):149. PMID: 32094348.
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Dandawate P, Ghosh C, Palaniyandi K, Paul S, Rawal S, Pradhan R, Sayed AAA, Choudhury S, Standing D, Subramaniam D, Padhye SB, Gunewardena S, Thomas SM, Neil MO, Tawfik O, Welch DR, Jensen RA, Maliski S, Weir S, Iwakuma T, Anant S, Dhar A. The Histone Demethylase KDM3A, Increased in Human Pancreatic Tumors, Regulates Expression of DCLK1 and Promotes Tumorigenesis in Mice. Gastroenterology. 2019 12; 157(6):1646-1659.e11. PMID: 31442435.
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Thoenen E, Curl A, Iwakuma T. TP53 in bone and soft tissue sarcomas. Pharmacol Ther. 2019 10; 202:149-164. PMID: 31276706.
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Han Y, Wu P, Wang Z, Zhang Z, Sun S, Liu J, Gong S, Gao P, Iwakuma T, Molina-Vila MA, Chen BP, Zhang Y, Ji T, Mo Q, Chen P, Hu J, Wang S, Zhou J, Lu H, Gao Q. Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation. EBioMedicine. 2019 Feb; 40:92-105. PMID: 30674441.
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Yamamoto S, Iwakuma T. Regulators of Oncogenic Mutant TP53 Gain of Function. Cancers (Basel). 2018 Dec 20; 11(1). PMID: 30577483.
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Ranjan A, Iyer SV, Ward C, Link T, Diaz FJ, Dhar A, Tawfik OW, Weinman SA, Azuma Y, Izumi T, Iwakuma T. MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma. Oncotarget. 2018 Apr 20; 9(30):21429-21443. PMID: 29765550.
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Ranjan A, Iwakuma T. Emerging Non-Canonical Functions and Regulation of p53. Int J Mol Sci. 2018 Mar 28; 19(4). PMID: 29597309.
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Parrales A, McDonald P, Ottomeyer M, Roy A, Shoenen FJ, Broward M, Bruns T, Thamm DH, Weir SJ, Neville KA, Iwakuma T, Fulbright JM. Comparative oncology approach to drug repurposing in osteosarcoma. PLoS One. 2018; 13(3):e0194224. PMID: 29579058.
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Parrales A, Thoenen E, Iwakuma T. The interplay between mutant p53 and the mevalonate pathway. Cell Death Differ. 2018 03; 25(3):460-470. PMID: 29238070.
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Dong S, Baranwal S, Garcia A, Serrano-Gomez SJ, Eastlack S, Iwakuma T, Mercante D, Mauvais-Jarvis F, Alahari SK. Nischarin inhibition alters energy metabolism by activating AMP-activated protein kinase. J Biol Chem. 2017 10 13; 292(41):16833-16846. PMID: 28842496.
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Kundu AK, Iyer SV, Chandra S, Adhikari AS, Iwakuma T, Mandal TK. Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma. PLoS One. 2017; 12(6):e0179168. PMID: 28636657.
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Link T, Iwakuma T. Roles of p53 in extrinsic factor-induced liver carcinogenesis. Hepatoma Res. 2017; 3:95-104. PMID: 30123836.
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Parrales A, Ranjan A, Iwakuma T. Unsaturated fatty acids regulate stemness of ovarian cancer cells through NF-?B. Stem Cell Investig. 2017; 4:49. PMID: 28607923.
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Yamamoto S, Iwakuma T. RIPK1-TRAF2 interplay on the TNF/NF-?B signaling, cell death, and cancer development in the liver. Transl Cancer Res. 2017 May; 6(Suppl 3):94-109. PMID: 30123738.
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Ranjan A, Iyer SV, Iwakuma T. Suppressive roles of A3AR and TMIGD3 i1 in osteosarcoma malignancy. Cell Cycle. 2017 05 19; 16(10):903-904. PMID: 28355102.
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Sasaki K, Kurahara H, Young ED, Natsugoe S, Ijichi A, Iwakuma T, Welch DR. Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer. Clin Exp Metastasis. 2017 04; 34(3-4):229-239. PMID: 28289921.
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Parrales A, Iwakuma T. p53 as a Regulator of Lipid Metabolism in Cancer. Int J Mol Sci. 2016 Dec 10; 17(12). PMID: 27973397.
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Ranjan A, Iwakuma T. Non-Canonical Cell Death Induced by p53. Int J Mol Sci. 2016 Dec 09; 17(12). PMID: 27941671.
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Braun MW, Iwakuma T. Regulation of cytotoxic T-cell responses by p53 in cancer. Transl Cancer Res. 2016 Dec; 5(6):692-697. PMID: 28944167.
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Iyer SV, Ranjan A, Elias HK, Parrales A, Sasaki H, Roy BC, Umar S, Tawfik OW, Iwakuma T. Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-?B and osteosarcoma progression. Nat Commun. 2016 11 25; 7:13561. PMID: 27886186.
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Parrales A, Ranjan A, Iyer SV, Padhye S, Weir SJ, Roy A, Iwakuma T. DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway. Nat Cell Biol. 2016 Nov; 18(11):1233-1243. PMID: 27775703.
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Kurahara H, Bohl C, Natsugoe S, Nishizono Y, Harihar S, Sharma R, Iwakuma T, Welch DR. Suppression of pancreatic cancer growth and metastasis by HMP19 identified through genome-wide shRNA screen. Int J Cancer. 2016 08 01; 139(3):628-38. PMID: 27012470.
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Ranjan A, Bera K, Iwakuma T. Murine double minute 2, a potential p53-independent regulator of liver cancer metastasis. Hepatoma Res. 2016; 2:114-121. PMID: 28944296.
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Iyer SV, Parrales A, Begani P, Narkar A, Adhikari AS, Martinez LA, Iwakuma T. Allele-specific silencing of mutant p53 attenuates dominant-negative and gain-of-function activities. Oncotarget. 2016 Feb 02; 7(5):5401-15. PMID: 26700961.
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Parrales A, Iwakuma T. Targeting Oncogenic Mutant p53 for Cancer Therapy. Front Oncol. 2015; 5:288. PMID: 26732534.
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Sasaki H, Iyer SV, Sasaki K, Tawfik OW, Iwakuma T. An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma. Anal Biochem. 2015 Oct 01; 486:70-4. PMID: 26142221.
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Bi Q, Ranjan A, Fan R, Agarwal N, Welch DR, Weinman SA, Ding J, Iwakuma T. MTBP inhibits migration and metastasis of hepatocellular carcinoma. Clin Exp Metastasis. 2015 Apr; 32(4):301-11. PMID: 25759210.
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Harihar S, Pounds KM, Iwakuma T, Seidah NG, Welch DR. Furin is the major proprotein convertase required for KISS1-to-Kisspeptin processing. PLoS One. 2014; 9(1):e84958. PMID: 24454770.
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Liu W, Beck BH, Vaidya KS, Nash KT, Feeley KP, Ballinger SW, Pounds KM, Denning WL, Diers AR, Landar A, Dhar A, Iwakuma T, Welch DR. Metastasis suppressor KISS1 seems to reverse the Warburg effect by enhancing mitochondrial biogenesis. Cancer Res. 2014 Feb 01; 74(3):954-63. PMID: 24351292.
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Iwakuma T, Agarwal N. MDM2 binding protein, a novel metastasis suppressor. Cancer Metastasis Rev. 2012 Dec; 31(3-4):633-40. PMID: 22684342.
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Iyer SV, Iwakuma T. A novel link between the HER2-Akt and MDM2-p53 pathways via CSN6. Cell Cycle. 2012 Nov 15; 11(22):4112. PMID: 23099920.
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Agarwal N, Adhikari AS, Iyer SV, Hekmatdoost K, Welch DR, Iwakuma T. MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4. Oncogene. 2013 Jan 24; 32(4):462-70. PMID: 22370640.
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Kibe R, Zhang S, Guo D, Marrero L, Tsien F, Rodriguez P, Khan S, Zieske A, Huang J, Li W, Durum SK, Iwakuma T, Cui Y. IL-7Ra deficiency in p53null mice exacerbates thymocyte telomere erosion and lymphomagenesis. Cell Death Differ. 2012 Jul; 19(7):1139-51. PMID: 22281704.
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Pant V, Xiong S, Iwakuma T, Quint?s-Cardama A, Lozano G. Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc Natl Acad Sci U S A. 2011 Jul 19; 108(29):11995-2000. PMID: 21730132.
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Zhang S, Zheng M, Kibe R, Huang Y, Marrero L, Warren S, Zieske AW, Iwakuma T, Kolls JK, Cui Y. Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis. FASEB J. 2011 Jul; 25(7):2387-98. PMID: 21471252.
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Zhao R, Yeung SC, Chen J, Iwakuma T, Su CH, Chen B, Qu C, Zhang F, Chen YT, Lin YL, Lee DF, Jin F, Zhu R, Shaikenov T, Sarbassov D, Sahin A, Wang H, Wang H, Lai CC, Tsai FJ, Lozano G, Lee MH. Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers. J Clin Invest. 2011 Mar; 121(3):851-65. PMID: 21317535.
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Agarwal N, Tochigi Y, Adhikari AS, Cui S, Cui Y, Iwakuma T. MTBP plays a crucial role in mitotic progression and chromosome segregation. Cell Death Differ. 2011 Jul; 18(7):1208-19. PMID: 21274008.
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Adhikari AS, Agarwal N, Iwakuma T. Metastatic potential of tumor-initiating cells in solid tumors. Front Biosci (Landmark Ed). 2011 01 01; 16(5):1927-38. PMID: 21196274.
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Post SM, Quint?s-Cardama A, Pant V, Iwakuma T, Hamir A, Jackson JG, Maccio DR, Bond GL, Johnson DG, Levine AJ, Lozano G. A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell. 2010 Sep 14; 18(3):220-30. PMID: 20832750.
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Adhikari AS, Agarwal N, Wood BM, Porretta C, Ruiz B, Pochampally RR, Iwakuma T. CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance. Cancer Res. 2010 Jun 01; 70(11):4602-12. PMID: 20460510.
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Odvody J, Vincent T, Arrate MP, Grieb B, Wang S, Garriga J, Lozano G, Iwakuma T, Haines DS, Eischen CM. A deficiency in Mdm2 binding protein inhibits Myc-induced B-cell proliferation and lymphomagenesis. Oncogene. 2010 Jun 03; 29(22):3287-96. PMID: 20305689.
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Adhikari AS, Iwakuma T. Mutant p53 gain of oncogenic function: in vivo evidence, mechanism of action and its clinical implications. Fukuoka Igaku Zasshi. 2009 Jun; 100(6):217-28. PMID: 19670804.
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Busso CS, Iwakuma T, Izumi T. Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway. Oncogene. 2009 Apr 02; 28(13):1616-25. PMID: 19219073.
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Barboza JA, Iwakuma T, Terzian T, El-Naggar AK, Lozano G. Mdm2 and Mdm4 loss regulates distinct p53 activities. Mol Cancer Res. 2008 Jun; 6(6):947-54. PMID: 18567799.
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Terzian T, Suh YA, Iwakuma T, Post SM, Neumann M, Lang GA, Van Pelt CS, Lozano G. The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss. Genes Dev. 2008 May 15; 22(10):1337-44. PMID: 18483220.
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Iwakuma T, Tochigi Y, Van Pelt CS, Caldwell LC, Terzian T, Parant JM, Chau GP, Koch JG, Eischen CM, Lozano G. Mtbp haploinsufficiency in mice increases tumor metastasis. Oncogene. 2008 Mar 20; 27(13):1813-20. PMID: 17906694.
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Iwakuma T, Lozano G. Crippling p53 activities via knock-in mutations in mouse models. Oncogene. 2007 Apr 02; 26(15):2177-84. PMID: 17401426.
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Iwakuma T, Lozano G, Flores ER. Li-Fraumeni syndrome: a p53 family affair. Cell Cycle. 2005 Jul; 4(7):865-7. PMID: 15917654.
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Lang GA, Iwakuma T, Suh YA, Liu G, Rao VA, Parant JM, Valentin-Vega YA, Terzian T, Caldwell LC, Strong LC, El-Naggar AK, Lozano G. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 2004 Dec 17; 119(6):861-72. PMID: 15607981.
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Iwakuma T, Parant JM, Fasulo M, Zwart E, Jacks T, de Vries A, Lozano G. Mutation at p53 serine 389 does not rescue the embryonic lethality in mdm2 or mdm4 null mice. Oncogene. 2004 Oct 07; 23(46):7644-50. PMID: 15361844.
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Bruins W, Zwart E, Attardi LD, Iwakuma T, Hoogervorst EM, Beems RB, Miranda B, van Oostrom CT, van den Berg J, van den Aardweg GJ, Lozano G, van Steeg H, Jacks T, de Vries A. Increased sensitivity to UV radiation in mice with a p53 point mutation at Ser389. Mol Cell Biol. 2004 Oct; 24(20):8884-94. PMID: 15456863.
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Iwakuma T, Lozano G. MDM2, an introduction. Mol Cancer Res. 2003 Dec; 1(14):993-1000. PMID: 14707282.
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Zhu K, Henning D, Iwakuma T, Valdez BC, Busch H. Adriamycin inhibits human RH II/Gu RNA helicase activity by binding to its substrate. Biochem Biophys Res Commun. 1999 Dec 20; 266(2):361-5. PMID: 10600508.
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Iwakuma T, Cui Y, Chang LJ. Self-inactivating lentiviral vectors with U3 and U5 modifications. Virology. 1999 Aug 15; 261(1):120-32. PMID: 10441560.
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Cui Y, Iwakuma T, Chang LJ. Contributions of viral splice sites and cis-regulatory elements to lentivirus vector function. J Virol. 1999 Jul; 73(7):6171-6. PMID: 10364378.
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Chang LJ, Urlacher V, Iwakuma T, Cui Y, Zucali J. Efficacy and safety analyses of a recombinant human immunodeficiency virus type 1 derived vector system. Gene Ther. 1999 May; 6(5):715-28. PMID: 10505094.
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Shinozaki K, Sato H, Iwakuma T, Sato R, Kurimoto T, Yoshida K. Synthesis and thromboxane A2 antagonistic activity activity of indane derivatives. Bioorg Med Chem Lett. 1999 Feb 08; 9(3):401-6. PMID: 10091692.
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Tsuzuki T, Kawate H, Iwakuma T. [Study on carcinogenesis and mutation suppression: repair of alkylation DNA damage and suppression of tumors]. Fukuoka Igaku Zasshi. 1998 Jan; 89(1):1-10. PMID: 9494281.
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Iwakuma T, Sakumi K, Nakatsuru Y, Kawate H, Igarashi H, Shiraishi A, Tsuzuki T, Ishikawa T, Sekiguchi M. High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase. Carcinogenesis. 1997 Aug; 18(8):1631-5. PMID: 9276640.
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Tanaka K, Iwakuma T, Harimaya K, Sato H, Iwamoto Y. EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells. J Clin Invest. 1997 Jan 15; 99(2):239-47. PMID: 9005992.
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1997 | 2 | 1998 | 1 | 1999 | 5 | 2003 | 1 | 2004 | 3 | 2005 | 1 | 2007 | 2 | 2008 | 2 | 2009 | 2 | 2010 | 3 | 2011 | 5 | 2012 | 4 | 2013 | 1 | 2014 | 1 | 2015 | 3 | 2016 | 8 | 2017 | 8 | 2018 | 4 | 2019 | 3 | 2020 | 3 | 2021 | 4 | 2022 | 2 | 2023 | 6 | 2024 | 3 |
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