Masahide Tone, PhD

Senior Scientist, Director of Research

Masahide Tone has led research groups in Molecular Biology, Immunology, Immunotherapy, and Cancer Immunology at Hoechst (Japan), the Universities of Cambridge and Oxford (UK), the University of Pennsylvania, and Cedars Sinai Medical Center.  His vast area of research expertise is in Molecular and Cellular Immunology including CRISPR gene editing, gene regulation, antibody engineering, cytokines, macrophages, dendritic cells, T-cells and regulatory T-cells (Treg).  In addition to his work as a researcher, Masahide has served as an Associate Editor for the Journal of Immunology and a Review Editor for Frontiers in Immunological Tolerance.  Throughout his research career he has mentored many post-doctoral fellows, graduate and undergraduate students.  His most recent work at Cedars Sinai Medical Center centered around the study of development and function of Treg to enhance Cancer Immunotherapy, and drug resistance  induced by differential gene expression in tumor environments. Masahide will bring his immense knowledge, vast skills, and leadership capabilities to the PMC lab as Senior Researcher and Director of Research.  See Masahide’s list of publications below.

Education

PhD Science (1985)

Tohoku Universirty, Japan

M.S. Science (1982)

Science University of Tokyo

B.S. Science (1980)

Science University of Tokyo

Lectures By Invitation:

Feb, 2004: The role of GITR and GITRL, Department of Pathology and Laboratory Medicine,
New Jersey Medical School
Jun, 2007: Differentiation of CD4+CD25+ regulatory T cell: regulation of FoxP3 gene expression
University of Oxford, UK
Dec, 2007:The role of Foxp3 transcription factor in regulating T cell-mediated immunity
Drexel University College of Medicine
Feb, 2008:Smad3 and NFAT cooperate to induceFoxp3 expression through its enhancer,
Keystone Symposia, Tolerance in transplantation and autoimmunity
May, 2008: Transcription factors involved in function and development of regulatory T cells.
National Institute of Health Science (Japan)
May, 2008: Transcription factors involved in function and development of regulatory T cells.
Department of Microbiology, School of Medicine, Keio University (Japan)
May, 2008: Transcription factors involved in regulatory T cell development.
Graduate School of Medicine and Faculty of Medicine, Osaka University
Jun, 2009: Transcriptional Regulation in CD4+CD25+ regulatory T cells
Kyoto T cell International Conference
Feb, 2009: Controlling development and function of Foxp3+ regulatory T cells
Cedars-Sinai Medical Center
Aug, 2009: Cancer Immunotherapy by inhibiting Foxp3 expression
University of Oxford, UK
Dec. 2011: Invited, Torrey Pines Institute for Molecular Studies
Aug. 2012: Foxp3 Gene Expression Regulation: Therapeutic Strategy by Controlling Treg
Development
Rigel Pharmaceuticals, Inc. USA
May. 2013: Role of Stat5 in regulating TGF- -mediated regulatory T cell (Treg) development
Rigel Pharmaceuticals, Inc. USA
Sep. 2016: Gene regulation by Foxp3 and from CAMPATH-1G to Alemtuzumab
Miyagi Cancer Center, Japan

 Publications

Tsuda M., Y. Tone, C. Ogawa, Y. Nagaoka, M. Katsumata, A. Necula, D. Howie, E. Masuda, H. Waldmann and Tone M. Regulation of the human FOXP3 gene determined through BAC reporter systems. Front. Immunol. 8:297 (2017).

Araki A., X. Liu, H. Kameda, Y. Tone, H. Fukuoka, M. Tone and S. Melmed. EGFR induces E2F1-mediated corticotroph tumorigenesis, Accepted (2017).

Araki T, Liu NA, Tone Y, Cuevas-Ramos D, Heltsley R, Tone M, Melmed S. E2F1-mediated human POMC expression in ectopic Cushing’s syndrome. Endocr. Relat. Cancer, 23: 857-870 (2016).

Liu NA, Araki T, Cuevas-Ramos D, Hong J, Ben-Shlomo A, Tone Y, Tone M, Melmed S. Cyclin EMediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease. J Clin Endocrinol Metab. 100:2557-64 (2015).

Liu, X, M. Kano, T. Araki, O. Cooper, H. Fukuoka, Y. Tone, M. Tone and S. Melmed. ErbB receptor-driven prolactinomas respond to targeted lapatinib treatment in female transgenic mice. Endocrinology 156: 71-9. (2015).

Tone, Y, Y. Kidani, C. Ogawa, K. Yamamoto, M. Tsuda, C. Peter, H. Waldmann and M. Tone, Gene expression in the Gitr locus is regulated by NF-kB and Foxp3 through an enhancer. J Immunol 192: 3915-24. (2014).

Ogawa, C., Y. Tone, M. Tsuda, C. Peter, H. Waldmann, and M. Tone. TGF-beta-Mediated Foxp3 Gene expression is cooperatively regulated by Stat5, Creb, and AP-1 through CNS2. J Immunol 192:475-483. (2014).

Chen, C. H., W. Zhou, S. Liu, Y. Deng, F. Cai, M. Tone, Y. Tone, Y. Tong, and W. Song. Increased NF-kappaB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease. Int J Neuropsychopharmacol:77-90. (2012).

Tone, M., and M. I. Greene.. Cooperative regulatory events and Foxp3 expression. Nat Immunol 12:14-16. (2011).

Ponte J.F., Ponath P., Gulati R., Slavonic M., Paglia M., O’Shea A., Tone M., Waldmann H., Vaickus L., Rosenzweig M.: Enhancement of humoral and cellular immunity with an anti-glucocorticoid-induced tumour necrosis factor receptor monoclonal antibody. Immunology. Feb 26 (2010).

Ruan Q., Kameswaran V., Tone Y., Li L., Liou H.C., Greene M.I., Tone M., Chen Y.H.: Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome. Immunity 31(6): 932-940, Dec (2009).

Howie D., Nolan K.F., Daley S., Butterfield E., Adams E., Garcia-Rueda H., Thompson C., Saunders N.J., Cobbold S.P., Tone Y., Tone M., Waldmann H.: MS4A4B is a GITR-associated membrane adapter, expressed by regulatory T cells, which modulates T cell activation. J. Immunol. 183(7): 4197-4204, Oct (2009).

Tone Y., Furuuchi K., Kojima Y., Tykocinski M.L., Greene M.I. and Masahide Tone: Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nature Immunology 9(2): 194-202, Feb (2008).

Tone M.: Transcription factors involved in development and function of regulatory T cells. Infection Inflammation Immunity (Japanese) 38, 24-35, (2008).

Zhou Z., Tone Y., Song X., Furuuchi K., Lear J.D., Waldmann H., Tone M., Greene M.I., Murali R.: Structural basis for ligand-mediated mouse GITR activation. Proc Natl Acad Sci USA 105(2): 641-645, Jan (2008) Notes: Shared corresponding author.

Tone Y., Kojima Y., Furuuchi K., Brady M., Yashiro-Ohtani Y., Tykocinski M.L. and Tone M.: OX40 gene expression is upregulated by chromatin remodeling in its promoter region containing Sp1/Sp3, YY1 and NF-kB binding sites. J. Immunol. 179(3), August (2007).

Nemeth Z.H., Lutz C.S., Csoka B. Deitch E.A. Leibovich S.J., Gause W.C., Tone M., Pacher P., Vizi E.S., and Hasko G.: Adenosine augments interleukin-10 production by macrophages through an A2B receptor-mediated post-transcriptional mechanism. J. Immunol.  175(12): 8260 – 8270, Dec (2005).

Yee C.S., Yao Y., Xu Q., McCarthy B., Sun-Lin D., Tone M., Waldmann H., Chang C.H..: Enhanced production of IL-10 by dendritic cells deficient in CIITA. J Immunol. 174(3): 1222-9, Feb (2005).

Waldmann H., Garaca L., Cobbold S., Adams E., Tone M., Tone Y.: Regulatory T cells and organ transplantation. Semin. Immunol. 16: 119-126, (2004).

Chandrasekar B., Marelli-Berg F.M., Tone M., Bysani S., Prabhu S.D., Murray D.R.: Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, Akt, IKK, and NF-kB. Biochem Biophys Res Commun 319(2): 304-311, June (2004).

Tone M., Tone Y., Adams E., Yates SF., Frewin MR., Cobbold SP., Waldmann H.: Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells.[see comment] Proc Natl Acad Sci USA 100(25): 15059-64, Dec 9 (2003).

Tone M., Tone Y., Babik JM., Lin CY., Waldmann H.: The role of Sp1 and NF-kappa B in regulating CD40 gene expression. J. Biol. Chem. 277(11): 8890-7, Mar 15 (2002).

Tone M., Tone Y., Fairchild PJ., Wykes M., Waldmann H.: Regulation of CD40 function by its isoforms generated through alternative splicing. Proc Natl Acad Sci USA 98(4): 1751-6, Feb 13 (2001).

Fairchild P.J., Brook F.A., Gardner R.L., Graça, Strong V., Tone Y., Tone M., Nolan K. F.and H. Waldmann: Directed differentiation of dendritic cells from mouse embryonic stem cells: A novel tool for identifying targets for immunotherapy. In: Pluripotent stem cells: properties, therapeutic perspective and ethical issues (2001).

Fairchild PJ., Brook FA., Gardner RL., Graca L., Strong V., Tone Y., Tone M., Nolan KF., Waldmann H.: Directed differentiation of dendritic cells from mouse embryonic stem cells. Current Biology 10(23): 1515-8, Nov 30 2000.

Tone M., Powell MJ., Tone Y., Thompson SA., Waldmann H.: IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3. J. Immunol. 165(1): 286-91, Jul 1 (2000).

Powell MJ., Thompson SA., Tone Y., Waldmann H., Tone M.: Posttranscriptional regulation of IL-10 gene expression through sequences in the 3′-untranslated region. J. Immunol.165(1): 292-6, Jul 1 (2000).

Fairchild P.j., Tone M., Strong V., and Nolan K.F. Spanning innate and adaptive immunity: a role for interleukin-18. In: Cytokine and cytokine receptors. Revillard JP (Ed). Gordon and Breach Academic Publishers. 284-299, (2000).

Tone M., Nolan KF., Walsh LA., Tone Y., Thompson SA., Waldmann H.: Structure and chromosomal location of mouse and human CD52 genes. Biochim. Biophy. Acta 1446(3): 334-40, Sep 3 (1999).

Babik JM., Adams E., Tone Y., Fairchild PJ., Tone M., Waldmann H.: Expression of murine IL-12 is regulated by translational control of the p35 subunit. J. Immunol. 162(7): 4069-78, Apr 1 (1999).

Gilliland LK., Walsh LA., Frewin MR., Wise MP., Tone M., Hale G., Kioussis D., Waldmann H.: Elimination of the immunogenicity of therapeutic antibodies. J. Immunol. 162(6): 3663-71, Mar 15 (1999).

Tone M., Diamond LE., Walsh LA., Tone Y., Thompson SA., Shanahan EM., Logan JS., Waldmann H.: High level transcription of the complement regulatory protein CD59 requires an enhancer located in intron 1. J. Biol. Chem. 274(2): 710-6, Jan 8 (1999).

Tone M., Thompson SA., Tone Y., Fairchild PJ., Waldmann H.: Regulation of IL-18 (IFN-gamma-inducing factor) gene expression. J. Immunol. 159(12): 6156-63, Dec 15 (1997).

Tone Y., Thompson SA., Babik JM., Nolan KF., Tone M., Raven C., Waldmann H.: Structure and chromosomal location of the mouse interleukin-12 p35 and p40 subunit genes. Eur. J. Immunol. 26(6): 1222-7, Jun (1996).

Diamond LE., McCurry KR., Oldham ER., Tone M., Waldmann H., Platt JL., Logan JS.: Human CD59 expressed in transgenic mouse hearts inhibits the activation of complement. Transplant Immunology 3(4): 305-12, Dec (1995).

Kooyman DL., Byrne GW., McClellan S., Nielsen D., Tone M., Waldmann H., Coffman TM., McCurry KR., Platt JL., Logan JS.: In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium. Science 269(5220): 89-92, Jul 7 (1995).

Mizuno S., Tajima S., Saitoh Y., Mori K., Ono H., Tone M., Mihira T.: Variation of repetitive DNA and its phylogenetic relation in Hynobiidae (Caudata). J. Heredity 86(2): 114-20, Mar-Apr (1995).

van der Merwe PA., Barclay AN., Mason DW., Davies EA., Morgan BP., Tone M., Krishnam AK., Ianelli C., Davis SJ.: Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. Biochemistry 33(33): 10149-60, Aug 23 (1994).

Diamond LE., Oldham ER., Platt JL., Waldmann H., Tone M., Walsh LA., Logan JS.: Cell- and tissue-specific expression of a human CD59 minigene in transgenic mice. Transplantation Proceedings 26(3): 1239, Jun (1994).

Liu GY., Baker D., Fairchild S., Figueroa F., Quartey-Papafio R., Tone M., Healey D., Cooke A., Turk JL., Wraith DC.: Complete characterization of the expressed immune response genes in Biozzi AB/H mice: structural and functional identity between AB/H and NOD A region molecules. Immunogenetics 37(4): 296-300, (1993).

Tone M., Walsh LA., Waldmann H.: Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation. J. Mol. Biol. 227(3): 971-6, Oct 5 (1992).

Walsh LA., Tone M., Thiru S., Waldmann H.: The CD59 antigen–a multifunctional molecule. Tissue Antigens 40(5): 213-20, Nov (1992).

Xia MQ., Tone M., Packman L., Hale G., Waldmann H.: Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur. J. Immunol. 21(7): 1677-84, Jul (1991).

Walsh LA., Tone M., Waldmann H.: Transfection of human CD59 complementary DNA into rat cells confers resistance to human complement. Eur. J. Immunol. 21(3): 847-50, Mar (1991).

Kondo S., Tone M., Teramoto N., Katayama I., Arai H., Nishioka K., Fujii K., Kobayashi Y., Nishiyama S.: [Clinical studies of 15 cases of progressive systemic sclerosis (PSS) associated with positive proteinuria and membranous glomerulonephritis]. [Japanese] Nippon Hifuka Gakkai Zasshi – Japanese Journal of Dermatology 99(10): 1105-10, Sep (1989).

Mikami S., Nishimura T., Naka H., Kuze K., Fukui H., Tone M., Hashimoto-Gotoh T.: Nonsense mutation in factor VIII gene of a severe haemophiliac patient with anti-factor VIII antibody. [Review] [23 refs] Jinrui Idengaku Zasshi [Japanese Journal of Human Genetics] 33(4): 409-15, Dec (1988).

Kodama H., Saitoh H., Tone M., Kuhara S., Sakaki Y., Mizuno S.: Nucleotide sequences and unusual electrophoretic behavior of the W chromosome-specific repeating DNA units of the domestic fowl, Gallus gallus domesticus. Chromosoma 96(1): 18-25, (1987).

Tone M., Kikuno R., Kume-Iwaki A., Hashimoto-Gotoh T.: Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. J. Biochemistry 102(5): 1033-41, Nov (1987).

Tone M., Sakaki Y., Hashiguchi T., Mizuno S.: Genus specificity and extensive methylation of the W chromosome-specific repetitive DNA sequences from the domestic fowl, Gallus gallus domesticus. Chromosoma 89(3): 228-37, (1984).

Tone M., Nakano N., Takao E., Narisawa S., Mizuno S.: Demonstration of W chromosome-specific repetitive DNA sequences in the domestic fowl, Gallus g. domesticus. Chromosoma 86(4): 551-69, (1982).