Yukikio Tone , DSc

Senior Researcher

Yukiko Tone is a Molecular Biologist whose skill set includes gene cloning, DNA/RNA/protein analysis, antibody engineering, BAC (Bacterial Artificial Chromosome) technology and CRISPR gene editing.  After finishing her academic studies, Yukiko moved to Great Britain where she studied molecular mechanisms of the thyroid hormone receptor at the University of Cambridge.  She then moved on to the University of Oxford where she worked on regulation of gene expression of cytokines (IL-12, IL-18 and IL-10) and TNF/TNFR superfamilies (CD40, OX40 and GITR, GITR ligand).  Later she worked at the University of Pennsylvania where she studied regulatory T-cell (Treg) mediated immune responses.  After moving to Los Angeles, she worked as a project scientist where she continued her work studying Foxp3 gene expression in Treg.  She recently focused on gene regulation in cancer cells to overcome drug resistance and to reduce cancer cell survivability in tumor microenvironments.  Her diverse research background and enormous dedication to her work make her an asset as a Senior Researcher on the PHLBI team.  See Yukikio’s list of publications below.

Education:

DSc Science

Tokyo Metropolition University, Japan (2002)

M.S. Science

Tokyo Metropolition University, Japan (1984)

B.S. Science

Tokyo Metropolition University, Japan (1982)

Publications

Tone Y, K. Yamamoto, R. Niwa, S. Harada, J-Z. Zhou, J. Said, W. Sabbagh, S. Alkan, H.P. Koeffler,
D. Li and M. Tone, Development of Rituximab (anti-CD20) resistance, in preparation

Tsuda M., Y. Tone (co-first author), 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. Frontiers in Immunology. In press 2017).

Takako 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. Endocrine-Related Cancer, Accepted (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 receptordriven
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 (co-first author), M. Tsuda, C. Peter, H. Waldmann, and M. Tone. TGF-betaMediated
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).

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).

Zhou Z., Tone Y (co-first author)., 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).

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

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).

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-gammainducing
factor) gene expression. J. Immunol. 159(12): 6156-63, Dec 15 (1997).

Collingwood TN., Butler A., Tone Y, Clifton-Bligh RJ., Parker MG and Chatterjee VKK. Thyroid
hormone-mediated enhancement of heterodimer formation between thyroid hormone receptor beta
and retinoid X receptor. J. Biol. Chem., 272, 13060-13065 (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).

Tone Y., Collingwood TN., Adams M. and Chatterjee VKK. Fuunctional analysis of a transactivation
domain in the thyroid hormone ß receptor. J. Biol. Chem., 269, 31157-31161 (1994)

Collingwood TN., Adams M., Tone Y. and Chatterjee VKK. Spectrum of transcriptional, dimerization,
and dominant negative properties of twenty different mutant thyroid hormone ß-Receptors in thyroid
hormone Resistance syndrome. Molecular Endocrinology, 8, 1262-1277 (1994)

Adams M., Matthews CH., Collinwood TN., Tone Y. and Chatterjee VKK., Genetic analysis of 29
kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel
mutation in the thyroid hormone receptor beta gene. J. Clin. Invest., 94, 506-515 (1994)

Matthews CH., Borgato S., Beck-peccoz P., Adams M., Tone Y., Gambino G. Primary amenorrhoea
and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Nat Genet. 5, 83-6
(1993)

Adams M., Nagaya T., Tone Y., Jameson JL. and Chatterjee VKK. (1992), Functional properties of a
novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance
syndrome Clin Endocrinol. 36, 281-9 (1992)

Iwahashi T., Tone Y., Usui J., Watanabe H., Sugawara I., Mori S., Okazaki H. Selective killing of
carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and
CEA-reactive cytorhodin-S antibody CA208. Cancer Immunol Immunother. 30, 239-46 (1989)

Kainosho M., Nagao H., Imamura-Tone Y., Uchida K., Tomonaga N., Nakamura Y., Tsuji T.
Structure sturdies of a protein using the assigned back-bone carbonyl carbon-13 NMR resonances.
J. Mol. Struc. 126, 549-562 (1985)