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Toshihiko Tanno, DVM, PhD

Academic Title:

Research Associate

Primary Appointment:

Surgery

Additional Title:

Division of Immunotherapy

Location:

N252, Institute of Human Virology, 725 W. Lombard St., Baltimore, MD 21201

Phone (Primary):

410-706-5890

Education and Training

1995-2001  Osaka Prefecture University, BVSc, Veterinary medicine  

2001-2005  Osaka Prefecture University, PhD, Veterinary science

2005-2010  National Institutes of Health, NIDDK, Visiting fellow, Hematology

2010-2013  Johns Hopkins University School of Medicine, Research fellow, Hematology/Oncology  

Biosketch

After PhD studies in molecular cell biology/biochemistry at Osaka Prefecture University, Dr. Tanno undertook a postdoc training in hematology at National Institute of Health. Using bioinformatics approach, he discovered a novel erythro-cytokine that regulated iron homeostasis. During the last postdoc period in Johns Hopkins University, he conducted a research about cancer stem-like cells (CSC) and found that a cytokine secreted from cancer microenvironment enhanced the CSC properties. These studies were published in major journals and led him focused to translational science in targeting medicine. His current works are development of aptamer-base targeting medicines that delivery nucleic acid therapeutics (miRNA, siRNA etc.) to desired cells in vivo. His newly designed small RNA targeting delivery platform in combination with bioinformatics approch allowed him to develop a novel therapeutic against various types of cancer. His research goal is to expand his invention and approach to a wide range of diseases.

Research/Clinical Keywords

Nucleic acid therapeutics, Targeting delivery, Hematology, Oncology, Bioinformatics

Highlighted Publications

  1. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, Moroney JW, Reed CH, Luban N, Wang RH, Eling T, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL. High level of GDF15 in thalassemia suppresses expression of the regulatory protein hepcidin. Nat. Med. 2007:13(9):1096-1101.
  2. Tanno T, Lim Y, Wang Q, Chesi M, Bergsagel PM, Matthews G, Johnstone RW, Ghosh N, Borrello I, Huff CA, and MatsuiWH. Growth differentiating factor 15 enhances the tumor-initiating and self-renewal potential of multiple myeloma cells. Blood 2014:123(5):725-733.
  3. Anchoori RK, Karanam B, Peng S, WangJ W, Jiang R, Tanno T, Orlowski R, Matsui W, Zhao M, Rudek MA, Hung C and Roden R. A bis-Benzylidine Piperidone Targeting Proteasome Ubiquitin Receptor RPN13 as a novel therapy for cancer. Cancer Cell. 2014:24(6):791-805.
  4. Agarwal JR, Wang Q, Tanno T, Rasheed Z, Merchant A, Ghosh N, Borrello I, Huff CA, Parhami F, Matsui W. Activation of liver x receptors inhibits hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma. Mol. Cancer Ther. 2014:13(7):1873-1881.
  5. Tanno T, Zhang P, Lazarski CA, Liu Y, Zheng P. An aptamer-based targeted delivery of miR-26a protects mice against chemotherapy toxicity while suppressing tumor growth. Blood Adv. 2017:1(15):1107-1119.

Additional Publication Citations

  1. Takenaka S, Takubo K, Watanabe F, Tanno T, Tsuyama S., Nakano Y., Tamura Y. Occurrence of coenzyme forms of vitamin B12 in a cultured purple laver (Porphyla yezoensis). Biosci. Biotechnol. Biochem. 2003:67(11):2480-2482.
  2. Tanno T, Takenaka S. Tsuyama S. Expression and function of Slit1α, a novel alternative splicing product for Slit1. J. Biochem. 2004:136(5):575-581.
  3. Takenaka S., Tanno T, Tsuyama S. Turning point for the research of Slit-Robo signaling. Radiation Biology Research Comunications 2004:39:408-416.
  4. Tanno T, Fujiwara A, Takenaka S, Kuwamura M, Tsuyama S. Expression of a chemorepellent factor Slit2 in peripheral nerve regeneration. Biosci. Biotechnol. Biochem. 2005:69(12):2431-2434.
  5. Tanno T, Tanaka Y, Sugiura T, Akiyoshi H, Takenaka S, Kuwamura M, Yamate J, Ohashi F, Kubo K, Tsuyama S. Expression Patterns of the slit Subfamily mRNA in Canine Malignant Mammary Tumors. J. Vet. Med. Sci. 2006:68(11):1173-1177.
  6. Tanno T, Fujiwara A, Sakaguchi K, Tanaka K, Takenaka S, Tsuyama S. Slit3 regulates Cell Motility through Rac/Cdc42 activation in Lipopolysaccharide-stimulated Macrophages. FEBS Lett. 2007:581(5):1022-1026.
  7. Tamary H, Shalev H, Peretz-Avraham G, Zoldan M, Tanno T, Miller J. High Levels of Growth Differentiation Factor 15 in Patients with Congenital Dyserythtopoietic Anemia Type I. Blood 2008:112(13):5241-5244.
  8. Zimmermann M, Winichagoon P, Sirankapracha P, Zeder C, Gowachirapant S, Tanno T,Miller J, Hurrell R, Fucharoen S. Iron metabolism in heterozygotes for HbE, α-thalassemia1 or β-thalassemia and compound heterozygotes for HbE/ β-thalassemia. Am. J. Clin. Nutri. 2008:88(4):1026-1031.
  9. Tanno T, Porayette P, Sripichai O, Noh SJ,Byrnes C,Bhupatiraju A, Lee YT, Goodnough JB,Harandi O, Ganz T, Paulson RF, Miller JL. Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 2009:114(1):181-186.
  10. Sripichai O, Kiefer CM, Bhanu NV, Tanno T, Noh SJ, Goh SH, Russell JE, Rognerud CL, Ou CN, Oneal PA, Meier ER, Gantt NM, Byrnes C, Lee YT, Dean A, and Miller JL. Cytokines increase fetal hemoglobin via mechanisms of globin gene histone modification and transcription factor reprogramming. Blood 2009:114(11):2299-2306.
  11. Tanno T, Rabel A, Lee TY, Yau YY, Leitman SF, Miller JL. Expression of growth differentiation factor 15 is not elevated in individuals with iron deficiency secondary to volunteer blood donation. Transfusion 2010:50(7):1532-1535.
  12. Tanno T, Miller JL.Growth differentiation factor 15 in health and disease. Curr. Opin. Hematol. 2010:17(3):184-190.  
  13. Tanno T, Miller JL. Iron loading and overloading due to ineffective erythropoiesis. Adv. Hematol. 2010:2010:358283.
  14. Cercamondi C, Egli I, Ahouandjinou E, Dossa R, Zeder C, Lamidhi S, Tjalsma H, Wiegerinck E, Tanno T, Miller J, Hurrell R, Hounhouigan J, Zimmermann M. Afebrile P. falciparum parasitemia decreases absorption of fortification iron but does not effect systemic iron utilization: a double stable isotope study in young Beninese women. Am. J. Clin. Nutri. 2010:92(6):1385-1392.
  15. Tanno T, Rabel EA,Alleyne M, Lee YT, Dahut W, Gulley JL, Miller JL. Hepcidin Expression and Iron-Restricted Anemia Among Prostate Cancer Research Subjects. BJU. Int. 2011:107(4):678-679.
  16. Tanno T, MillerJL. GDF15 expression and iron overload in ineffective erythropoiesis. Rinsho Ketsueki. 2011:52:389-398.
  17. Tanno T, Matsui W. Development and maintenance of cancer stem cells under chronic inflammation. J Nippon Med Sch. 2011:78(3):138-145.
  18. Tanno T, Matsui WH. Stem cell theory and inflammation-related cancer (Chapter 2). In: Kawanish S and Ohoshima H eds. Cancer and Inflammation Mechanisms: Chemical, Biological, and Clinical Aspects. John Wiley & Sons, Inc, 2014.
  19. Ittiprasert W, Mann VH, Karinshak SE, Coghlan A, Rinaldi G, Sankaranarayanan G, Chaidee A, Tanno T, Kumkhaek C, Prangtaworn P, Mentink-Kane M, Cochran CJ, Driguez P, Holroyd N, Tracey A, Rodpai R, Everts B, Hokke CH, Hoffmann KF, Berriman M, Brindley PJ, Programmed genome editing of the omega-1 ribonucleaseof the blood fluke, Schistosomamansoni. eLife. 2018:7:e41337. 
  20. Zhang Y, Tanno T, Kanellopoulou C. Cancer therapeutic implications of microRNAs in the regulation ofimmune checkpoint blockade. ExRNA. 2019, 1:19

Research Interests

The recent rapid expansion of genomic data greatly contributes to the understanding of disease development and progression. To translate these genetic discoveries into clinical applications, we need to develop therapeutic platforms that can specifically modulate the expression of disease-related genes in target cells in vivo. Small RNAs, such as microRNAs and siRNAs function in messenger RNA silencing and post-transcriptional regulation of gene expression. Given the challenge of targeting delivery of the small RNAs to specific cells and tissues in vivo, Dr. Tanno developed a small RNA targeting delivery platform, comprising a miRNA/siRNA sequence, a cell surface receptor-targeting DNA aptamer (a “chemical antibody”), and cholesterol. This newly designed delivery platform combines all the desired attributes of a small RNA targeting molecule by enabling the specific delivery of miRNA or siRNA into the desired cells through the targeting aptamers and increasing half-life by limiting nuclease degradation and renal excretion. Furthermore, these three components are assembled together by complementary base pairing of the RNA nucleic acid sequences, thus creating a highly versatile platform in which the therapeutic or targeting moieties can be changed to suit the intended purpose or target indication (patent pending). Using this platform, Dr. Tanno aims to develop novel therapeutics and research tools for a wide range of diseases. Current research interests are 1) applying the platform to breast and lung cancer therapies, 2) applying the platform to cancer immunotherapy, 3) screening aptamers targeting cancer specific glycosylation, and 4) developing new targeting delivery platform that can deliver various types of nucleic acids.

 

Awards and Affiliations

2001                Japan National License for Veterinary Medicine (DVM)

2001-2005       Japan Student Service Organization (JASSO) Scholarship

2005                Awarded trainee for Korea-China-Japan Joint-Bioinformatics Training Course, Japan Science and Technology Agency (JST)

2007                Novartis President’s Award, International BioIron Society, awarded for best young scientist presentation at 2nd annual meeting 

2011-2013       Ruth L. Kirschstein National Research Service Award (NRSA), NHLBI/Johns Hopkins University

2013-2018       Staff Scientist, Center for Cancer and Immunology Research, Children's National Medical Center 

2018-present    Faculty Research Associate, Division of Immunotherapy, Institute of Human Virology, University of Maryland Schoold of Medicine, Baltimore