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Tomoo Iwakuma, MD, PhD

Professor
Frank B. Tyler Professor of Cancer Research
Adjunct faculty, Department of Molecular & Integrative Physiology, KUMC
Director, Translational Laboratory Oncology Research Program at the Children's Mercy Research Institute
M.D.: 1991, Kyushu University
Ph.D.: 1997, Kyushu University
Postdoctoral: 1997-2005, University of Florida, MD Anderson Cancer Center
Assistant Professor: 2005-2011, Louisiana State University Health Sciences Center
Associate Professor: 2011-2018, KUMC
Assistant Professor: 2005-2011, Louisiana State University Health Sciences Center


Dr. Iwakuma's primary research focuses on the field of Cancer Research, specifically on cancer progression including liver cancer, and head and neck squamous cell carcinoma, and bone and soft tissue sarcoma. Over 50% of human cancers have mutations in the tumor suppressor p53 which regulates cell cycle progression, cell death, senescence, chromosome integrity, DNA repair, metabolism, and metastasis. Therefore, understanding of the pathway involved in the regulation of p53 is essential for discovering novel cancer therapies. With special focus on the tumor suppressor p53 pathway, Dr. Iwakuma dissects the mechanism of cancer progression using several mouse models, attempts to discover novel compounds to target the p53 pathway, and applies disease models to translational research, to ultimately cure cancer.

Lab Members

Alejandro Parrales, PhD
Postdoctoral Fellow

Atul Ranjan, PhD
Postdoctoral Fellow

 

Alalem Mohamed, PhD
Postdoctoral Fellow

 

Elizabeth Thoenen
Graduate Student

Hongyi Ren
Graduate Student

 

Satomi Yamamoto, MD
Research Assistant

 

 

 

 

 

 

 

 

 



Selected Publications (out of 65)


1. Iwakuma T, Lozano G.  Mdm2, an Introduction.  Mol. Cancer Res. 2003; 1 (14): 993-1000. Review. PMID: 14707282 #The top4 most cited paper in year 2007~2013.  

2. Iwakuma T, Parant JM, Fasulo Jr 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; 23 (46): 7644-7650. PMID: 15361844  

3. Lang GA*, Iwakuma T*, Suh A-Y, 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; 119 (6): 861-872. *These two authors contributed equally to this study. PMID: 15607981    

4. Iwakuma T#, Tochigi Y, Van Pelt CS, Caldwell LC, Terzian T, Parant JM, Chau GP, Koch J, Eischen CM, Lozano G#. Mtbp haploinsufficiency in mice increases tumor metastasis. Oncogene 2008; 27(13):1813-1820.  PMID: 17906694.  

5. Terzian T, Suh Y-A, 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 & Development 2008; 22(10): 1337-1344. PMID: 18483220. PMCID: PMC2377188  

6. Adhikari A, Agarwal N, Wood BM, Constance P, Pochampally RR, and Iwakuma T#. CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance. Cancer Research 2010; 70(11): 4602-4612. PMID: 20460510.  

7. Post SM, Quintás-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; 18(3):220-230. PMID: 20832750, PMCID: PMC2944041  

8. Agarwal N, Tochigi Y, Amit S. Adhikari AS, Cui S, Cui Y, and Iwakuma T#. MTBP plays a crucial role in mitotic progression and chromosome segregation. Cell Death & Differentiation 2011; 18, 1208-1219; doi:10.1038/cdd.2010.189; PMID: 21274008, PMCID: PMC3131950  

9. Pant V, Xiong S, Iwakuma T, Quintas-Cardama A, and Lozano G. Mdm2-Mdm4 heterodimerization is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc. Natl. Acad. Sci. USA. 2011; 108(29):11995-2000. PMID: 21730132, PMCID: PMC3141986.  

10. Iwakuma T# and Agarwal N. MDM2 Binding Protein, a novel metastasis suppressor, Cancer Metastasis Review 2012; 31(3-4):633-640. PMID: 22684342. doi: 10.1007/s10555-012-9364-x.

11. Agarwal N, Adhikari AS, Iyer SV, Hekmatdoost K, Welch DR, and Iwakuma T#. MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4. Oncogene 2013; 32(4):462-70. PMID:22370640.  

12. Bi Q*, Ranjan A*,Fan R, Agarwal N, Welch DR, Weinman SA, Ding J#Iwakuma T#.  MTBP suppresses metastasis in hepatocellular carcinoma. Clinical and Experimental Metastasis 2015; 32(4):301-11. PMID: 25759210. PMCID: PMC4510982.

13. Sasaki H, Iyer SV, Sasaki K, Tawfik O, and Iwakuma T#. An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma, Analytical Biochemistry 2015; 486:70-74. PMID: 26142221. PMCID: PMC4537805.

14. Iyer SV, Parrales A, Begani P, Narkar A, Adhikari AS, Martinez LA, Iwakuma T#. Allele-specific siRNA silencing for p53 mutants for p53 mutants attenuates their dominant-negative gain-of-function activities. Oncotarget 2016; 7(5):5401-15. doi: 10.18632/oncotarget.6634. PMID: 26700961, PMICD: PMC4868694.

15. Parrales A, Ranjan A, Iyer SV, Padhye S, Weir SJ, Roy A, Iwakuma T#. DNAJA1 controls the fate of misfolded mutant p53 via the mevalonate pathway. Nature Cell Biology 2016; 18(11):1233-1243. PMID: 27775703, PMCID: PMC5340314.

16. Iyer SV, Ranjan A, Elias HK, Parrales A, Sasaki H, Roy BC, Umar, S, Tawfik OW, Iwakuma T#. TMIGD3 isoform 1 suppresses osteosarcoma progression via the NF-κB pathway. Nature Communications 20165; 7:13561. PMID: 27886186, PMCID: PMC5133659. 

17. 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;34(3-4):229-239. PMID: 28289921, PMCID: PMC5450640.

18. Ranjan A, Iyer SV, Ward C, Link T, Diaz FJ, Dhar A, Tawfik O, Weinman S, Azuma Y, Izumi T, Iwakuma T#. MTBP inhibits the Erk1/2-Elk1 pathway to inhibit HCC migration. Oncotarget 2018; 9:21429-21443. PMID: 29765550, PMCID: PMC5940416.  

19. Parrales A, Thoenen E, Iwakuma T#. The interplay between mutant p53 and the mevalonate pathway. Cell Death Differ. 2018; 25(3):460-470. PMID: 29238070, PMCID: PMC5864191.  

20. 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; 26;13(3):e0194224. PMID: 29579058 PMCID: PMC5868798  

Last modified: Aug 15, 2018

Tomoo Iwakuma, MD, PhD

Contact

Tomoo Iwakuma, MD, PhD
Professor
Frank B. Tyler Professor of Cancer Research
Adjunct faculty, Department of Molecular & Integrative Physiology, KUMC
Director, Translational Laboratory Oncology Research Program at the Children's Mercy Research Institute

2005 Wahl East, Mailstop 1027
3901 Rainbow Boulevard
Kansas City, KS 66160

P: (913) 588-7412
tiwakuma@kumc.edu

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