Virginia Commonwealth University

Make it real.

Featured Researcher

Research Expertise and Focus

Breast Cancer, Role of Sphingosine-1-phosphate in breast cancer progression

Professional Highlights


  • Scholar, Building Interdisciplinary Research Careers in Women’s Health (BIRCWH)
  • Fellow, American College of Surgeons
  • Visiting Professor, Noguchi Medical Institute, 2008
  • Surgical Oncology Fellow, Virginia Commonwealth University, 2006-2008

Education and Training

  • Ph.D, Yokohama City University, Yokohama, Japan.
  • M.D., Niigata University School of Medicine, Niigata, Japan

Selected Publications

Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol. 2015 Apr 15;7(4):17-29. doi: 10.4251/wjgo.v7.i4.17. Review. PubMed PMID: 25897346; PubMed Central PMCID: PMC4398892.

Nagahashi M, Takabe K, Liu R, Peng K, Wang X, Wang Y, Hait NC, Wang X, Allegood JC, Yamada A, Aoyagi T, Liang J, Pandak WM, Spiegel S, Hylemon PB, Zhou  H. Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression. Hepatology. 2015 Apr;61(4):1216-26. doi: 10.1002/hep.27592. Epub 2015 Mar 9. PubMed PMID: 25363242; PubMed Central PMCID: PMC4376566.

Aoki M, Aoki H, Ramanathan R, Hait NC, Takabe K. Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential. Mediators Inflamm. 2016;2016:8606878. doi: 10.1155/2016/8606878. Epub 2016 Feb 7. Review. PMID: 26966342 Free PMC Article

Tsuchida J, Nagahashi M, Rashid OM, Takabe K, Wakai T. At what age should screening mammography be recommended for asian women? Cancer Med. 2015 Jul;4(7):1136-1144. PMCID: PMC4529351

Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol. 2015 Apr 15;7(4):17-29. PMCID: PMC4398892

Rashid OM, Takabe K. Animal models for exploring the pharmacokinetics of breast cancer therapies. Expert Opin Drug Metab Toxicol. 2015 Feb;11(2):221-230. PMCID: PMC4583421

Raza A, Takabe K, Wolfe LG, Lockhart CG, Kim RH. Outcomes of hybrid video assisted thoracoscopic surgery for pulmonary metastasectomy. J Surg Sci. 2014 Dec;2(1):18-24. PMCID: PMC4332393

Ishikawa T, Ichikawa Y, Shimizu D, Sasaki T, Tanabe M, Chishima T, Takabe K, Endo I. The role of HER-2 in breast cancer. J Surg Sci. 2014 Dec;2(1):4-9. PMCID: PMC4323095

Rashid OM, Nagahashi M, Ramachandran S, Dumur C, Schaum J, Yamada A, Terracina KP, Milstien S, Spiegel S, Takabe K. An improved syngeneic orthotopic murine model of human breast cancer progression. Breast Cancer Res Treat. 2014 Oct;147(3):501-512. PMCID: PMC4176514

Ishikawa T, Sasaki T, Tanabe M, Narui K, Kida K, Shimada K, Shimizu D, Yamada A, Morita S, Oba MS, Kawachi K, Nozawa A, Ichikawa Y, Takabe K, Endo I. The pathological response to anthracycline is associated with topoisomerase IIalpha gene amplification in the HER2 breast cancer subset. J Surg Sci. 2014 Dec;2(1):10-12. PMCID: PMC4309011

Takabe K, Spiegel S. Export of sphingosine-1-phosphate and cancer progression. J Lipid Res. 2014 Sep;55(9):1839-1846. PMCID: PMC4617347

Aoyagi T, Terracina KP, Raza A, Takabe K. Current treatment options for colon cancer peritoneal carcinomatosis. World J Gastroenterol. 2014 Sep 21;20(35):12493-12500. PMCID: PMC4168082

Raza A, Huang WC, Takabe K. Advances in the management of peritoneal mesothelioma. World J Gastroenterol. 2014 Sep 7;20(33). PMCID: PMC4155360

Harikumar KB, Yester JW, Surace MJ, Oyeniran C, Price MM, Huang WC, Hait NC, Allegood JC, Yamada A, Kong X, Lazear HM, Bhardwaj R, Takabe K, Diamond MS, Luo C, et al. K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5. Nat Immunol. 2014 Mar;15(3):231-238. PMCID: PMC3976678

Rashid OM, Takabe K. Does removal of the primary tumor in metastatic breast cancer improve survival? J Womens Health (Larchmt). 2014 Feb;23(2):184-188. PMCID: PMC3922396

Arora TK, Terracina KP, Soong J, Idowu MO, Takabe K. Primary and secondary angiosarcoma of the breast. Gland Surg. 2014 Feb;3(1):28-34. PMCID: PMC4115777

Nagahashi M, Hait NC, Maceyka M, Avni D, Takabe K, Milstien S, Spiegel S. Sphingosine-1-phosphate in chronic intestinal inflammation and cancer. Adv Biol Regul. 2014 Jan;54112-120. PMCID: PMC3946530

Nagahashi M, Takabe K, Terracina KP, Soma D, Hirose Y, Kobayashi T, Matsuda Y, Wakai T. Sphingosine-1-phosphate transporters as targets for cancer therapy. Biomed Res Int. 2014;2014651727. PMCID: PMC4123566

Takabe K. Welcome to the. J Surg Sci. 2013 Dec;1(1):1-2. PMCID: PMC4225642

Nagahashi M, Aoyagi T, Yamada A, Rashid OM, Adams BJ, Takabe K. Intestinal co-infection of tuberculosis and CMV can cause massive lower GI bleeding in a patient with HIV. J Surg Sci. 2013 Dec 1;1(1):12-15. PMCID: PMC4109321

Rashid OM, Nagahashi M, Ramachandran S, Graham L, Yamada A, Spiegel S, Bear HD, Takabe K. Resection of the primary tumor improves survival in metastatic breast cancer by reducing overall tumor burden. Surgery. 2013 Jun;153(6):771-8. PMCID: PMC3664113

Rashid OM, Nagahashi M, Ramachandran S, Dumur CI, Schaum JC, Yamada A, Aoyagi T, Milstien S, Spiegel S, Takabe K. Is tail vein injection a relevant breast cancer lung metastasis model. J Thorac Dis. 2013 Aug;5(4):385-92. PMCID: PMC3755653

Miyazaki H, Takabe K, Yeudall WA. Chemokines, chemokine receptors and the gastrointestinal system. World J Gastroenterol. 2013 May 21;19(19):2847-2863. PMCID: PMC3660811

Rashid OM, Cassano AD, Takabe K. Thymic neoplasm: A rare disease with a complex clinical presentation. J Thorac Dis. 2013 Apr;5(2):173-183. PMCID: PMC3621939

Rashid OM, Nagahashi M, Takabe K. Minimally invasive colostomy revision for palliation of large stomal prolapse and an adherent sliding peristomal hernia. Am Surg. 2013 Apr;79(4):E167-8. PMCID: PMC3671947

Trebska-McGowan K, Terracina KP, Takabe K. Update on the surgical management of paget’s disease. Gland Surg. 2013 Aug 1;2(3):10.3978/j.issn.2227-684X.2013.08.03. PMCID: PMC3876799

Yamada A, Ishikawa T, Takabe K, Endo I. Earwax type and osmidrosis: Prognostic factor for breast cancer? response to letter to the editor. Breast Cancer Res Treat. 2013 Apr;138(2):652-653. PMCID: PMC3707799

Nagahashi M, Kim EY, Yamada A, Ramachandran S, Allegood JC, Hait NC, Maceyka M, Milstien S, Takabe K, Spiegel S. Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network. Faseb J. 2013 Mar;27(3):1001-1011. PMCID: PMC3574288

Yamada A, Ishikawa T, Ota I, Kimura M, Shimizu D, Tanabe M, Chishima T, Sasaki T, Ichikawa Y, Morita S, Yoshiura K, Takabe K, Endo I. High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. Breast Cancer Res Treat. 2013 Feb;137(3):773-782. PMCID: PMC3560367

Huang WC, Nagahashi M, Terracina KP, Takabe K. Emerging role of sphingosine-1-phosphate in inflammation, cancer, and lymphangiogenesis. Biomolecules. 2013;3(3):10.3390/biom3030408. PMCID: PMC3839861

Liang J, Nagahashi M, Kim EY, Harikumar KB, Yamada A, Huang WC, Hait NC, Allegood JC, Price MM, Avni D, Takabe K, Kordula T, Milstien S, Spiegel S. Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer. Cancer Cell. 2013 Jan 14;23(1):107-120. PMCID: PMC3578577

Rashid AM, Williams C, Noble J, Rashid OM, Takabe K, Anand RJ. Pneumothorax, an underappreciated complication with an airway exchange catheter. J Thorac Dis. 2012 Dec;4(6):659-62. PMCID: PMC3506810

Yamada A, Takabe K. Should we examine sentinel lymph nodes during the operation? Gland Surg. 2012 Nov 1;1(3):161-163. PMCID: PMC4018831

Rashid OM, Ku JK, Nagahashi M, Yamada A, Takabe K. Inverted Meckel’s diverticulum as a cause of occult lower gastrointestinal hemorrhage. World J Gastroenterol. 2012 Nov 14;18(42):6155-9. PMCID: PMC3496894

Aoyagi T, Nagahashi M, Yamada A, Takabe K. The role of sphingosine-1-phosphate in breast cancer tumor-induced lymphangiogenesis. Lymphat Res Biol. 2012 Sep;10(3):97-106. PMCID: PMC3444762

Takabe K, Yamada A, Rashid OM, Adams BJ, Huang WC, Aoyagi T, Nagahashi M. Twofer anti-vascular therapy targeting sphingosine-1-phosphate for breast cancer. Gland Surg. 2012 Aug 1;1(2):80-83. PMCID: PMC4027044

Rashid OM, Takabe K. Are video-assisted thoracoscopic surgery (VATS) and robotic video-assisted thoracic surgery (RVATS) for pulmonary resection ready for prime time? J Thorac Dis. 2012 Aug; 4(4): 341–2. PMCID: PMC3426748

Rashid OM, Takabe K. The evolution of the role of surgery in the management of breast cancer lung metastasis. J Thorac Dis. 2012 Aug; 4(4): 420-4.  PMCID: PMC3426738

Adams BJ, Goldberg S, Massey HD, Takabe K. A cause of unbearably painful breast, diffuse dermal angiomatosis. Gland Surg. 2012 Aug 1;1(2):10.3978/j.issn.2227-684X.2012.07.02. PMCID: PMC3864042

Seitelman E, Arellano JJ, Takabe K, Barrett L, Faust G, Angus LD. Chylothorax after blunt trauma. J Thorac Dis. 2012 Jun 1;4(3):327-330. PMCID: PMC3378189

Rashid OM, Nagahashi  M, Takabe K. Management of massive soft tissue defects: The use of INTEGRA® artificial skin after necrotizing soft tissue infection of the chest. J Thorac Dis. 2012 Jun 1; 4(3): 331-5.  PMCID: PMC3378193

Rashid OM, Takabe K. Sentinel lymph node biopsy for breast cancer: Our technique and future directions in lymph node staging. J Nucl Med Radiat Ther. 2012 May 28;2012(S2):005. PMCID: PMC3600158

Stevenson CE, Nagahashi M, Ramachandran S, Yamada A, Bear HD, Takabe K. Bevacizumab and breast cancer: What does the future hold? Future Oncol. 2012 Apr;8(4):403-414. PMCID: PMC3464486

Nagahashi M, Ramachandran S, Kim EY, Allegood JC, Rashid OM, Yamada A, Zhao R, Milstien S, Zhou H, Spiegel S, Takabe K. Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis. Cancer Res. 2012 Feb 1;72(3):726-735. PMCID: PMC3289261

Studer E, Zhou X, Zhao R, Wang Y, Takabe K, Nagahashi M, Pandak WM, Dent P, Spiegel S, Shi R, Xu W, Liu X, Bohdan P, Zhang L, Zhou H, et al. Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes. Hepatology. 2012 Jan;55(1):267-276. PMCID: PMC3245352

Stevenson CE, Takabe K, Nagahashi M, Milstien S, Spiegel S. Targeting sphingosine-1-phosphate in hematologic malignancies. Anticancer Agents Med Chem. 2011 Nov;11(9):794-798. PMCID: PMC3368248

Seitelman E, Donenfeld P, Kay K, Takabe K, Andaz S, Fox S. Successful treatment of primary pulmonary melanoma. J Thorac Dis. 2011 Sep; 3(3): 207-8. PMCID: PMC3256523

Takabe K. Is T790M mutation the key in development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)? J Thorac Dis. 2011 Mar;3(1):1-3. PMCID: PMC3256500

Kim RH, Takabe K, Lockhart CG. Outcomes of a hybrid technique for video-assisted thoracoscopic surgery (VATS) pulmonary resection in a community setting. J Thorac Dis. 2010 Dec;2(4):210-214. PMCID: PMC3256472

Ramachandran S, Shida D, Nagahashi M, Fang X, Milstien S, Takabe K, Spiegel S. Lysophosphatidic acid stimulates gastric cancer cell proliferation via ERK1-dependent upregulation of sphingosine kinase 1 transcription. FEBS Lett. 2010 Sep 24;584(18):4077-4082. PMCID: PMC2947956

Nagahashi M, Ramachandran S, Rashid OM, Takabe K. Lymphangiogenesis: A new player in cancer progression. World J Gastroenterol. 2010 Aug 28;16(32):4003-4012. PMCID: PMC2928453

Kim RH, Takabe K, Milstien S, Spiegel S. Export and functions of sphingosine-1-phosphate. Biochim Biophys Acta. 2009 Jul;1791(7):692-696. PMCID: PMC2763566

Takabe K, Kim RH, Allegood JC, Mitra P, Ramachandran S, Nagahash M, Kuzhuvelil B. Harikumar KB, Nitai C. Hait NC, Milstien S, Spiegel S. Estradiol Induces Export of Sphingosine 1-Phosphate from Breast Cancer Cells via ABCC1 and ABCG2. J Biol Chem. 2010 Apr 2; 285(14): 10477-86. PMCID: PMC2856255

Takabe K, Paugh SW, Milstien S, Spiegel S. “Inside-out” signaling of sphingosine-1-phosphate: Therapeutic targets. Pharmacol Rev. 2008 Jun;60(2):181-195. PMCID: PMC2695666

Shida D, Fang X, Kordula T, Takabe K, Lepine S, Alvarez SE, Milstien S, Spiegel S. Cross-talk between LPA1 and epidermal growth factor receptors mediates up-regulation of sphingosine kinase 1 to promote gastric cancer cell motility and invasion. Cancer Res. 2008 Aug 15;68(16):6569-6577. PMCID: PMC2763580

Shida D, Takabe K, Kapitonov D, Milstien S, Spiegel S. Targeting SphK1 as a new strategy against cancer. Curr Drug Targets. 2008 Aug;9(8):662-673. PMCID: PMC2674575