Download PHS 398 (Rev. 9/04), Biographical Sketch Format

Principal Investigator/Program Director (Last, First, Middle):
Yu, Hua, Eleanor
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Hua Eleanor Yu, Ph.D.
Professor, Associate Chair, Dept of CITI
Co-Director, Cancer Immunotherapy Program, City
of Hope NCI Comprehensive Cancer Center
eRA COMMONS USER NAME
HUAEYU
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
Columbia University, New York, NY
Columbia University, New York, NY
University of Michigan, Ann Arbor, MI
DEGREE
(if applicable)
B.A.
Ph.D.
Postdoc
YEAR(s)
1983
1988
1989-1992
FIELD OF STUDY
Biology
Molecular Biology
Molecular Biology
A. Personal Statement
My laboratory was the first to show that STAT3 is a target for cancer therapy in animal tumor models. An
unexpected tumor-killing effect (bystander effect) in vivo led us uncover a link between STAT3 and tumor
immune evasion, first in tumor cells, and later in the tumor stromal cells, including many types of immune cells.
At the molecular level, my lab has also made a few discoveries, providing mechanisms by which STAT3
induces tumor immune suppression, tumor growth and inflammation while inhibiting antitumor immune
responses. Recent studies in my laboratory further demonstrate a critical role of S1P-S1PR1 in persistent
activation of STAT3 in tumor cells, in various tumor stromal cells, including myeloid cells, endothelial cells,
CD4 T cells and fibroblasts. This signaling pathway is also crucial in mediating the crosstalk between tumor
cells and various cells in the tumor microenvironment in forming niches, providing sanctuary for tumor cells to
survive and proliferate, and important for this grant application, a potential role in mediating drug resistance.
B. Positions and Honors
1982-1983
Helena Rubinstein Foundation Scholarship (undergraduate), Columbia University
1983-1988
Faculty Fellow, Columbia University
1989
NIH Postdoctoral Training Grant Fellowship
1990-1992
American Cancer Society Postdoctoral Fellowship
(Childcare leave)
1994-1995
Research Scientist: Department of Microbiology and Immunology, University of Michigan.
1995-2002
Assistant Professor: Immunology Program, Moffitt Cancer Research Center
2002-2005
Associate Professor: Immunology Program, Moffitt Cancer Research Center
2004
Scientist of the Year, H. Lee Moffitt Cancer Center and Research Institute
2005-2008
Member, CII Study Section, National Institutes of Health, National Cancer Institute
2005-present Professor
2010-present Associate Chair, Department of Cancer Immunotherapeutics and Tumor Immunology
Beckman Research Institute at City of Hope National Medical Center
Co-Director, Cancer Immunotherapy Program, City of Hope Comprehensive Cancer Center
C. Recent and/or selected publications (from a total of 70+ publications)
 Lee H, Deng J, Kujawski M, Liu Y, Herrmann A, Kortylewski M, Horne D, Forman S, Jove R and Yu H. 2010.
Stat3-induced expression of S1P1 receptor for the sphingolipid metabolite S1P is critical for persistent
Stat3 activation in tumors. Nature Medicine. 16(12):1421-8. PMID: 21102457.
 Kujawski M, Zhang CY, Herrmann A, Reckamp K, Scuto A, Jensen M, Deng JH, Forman S, Figlin R and Yu
H. 2010. Targeting Stat3 in adoptively transferred T cells promotes their in vivo expansion and antitumor
effects. Cancer Research. 70(23):9599-610. PMID: 21118964.
 Wang L, Yi TS, Zhang W, Pardoll D and H Yu. 2010. IL-17 enhances tumor development in carcinogeninduced skin cancer. Cancer Research. 70(24):10112-20. PMID: 21159818.
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Yu, Hua, Eleanor
Herrmann A, Kortylewski M, Kujawski M, Zhang C, Reckamp K, Armstrong B, Wang L, Kowolik C, Deng J
Figlin R and Yu H. 2010. Targeting Stat3 in the myeloid compartment drastically improves the in vivo
antitumor functions of adoptively transferred T cells. Cancer Research. 70(19):7455-64. PMID: 20841481.
Hedvat M, Huszar M, Herrmann A, Gozgit JM, Schroeder A, Sheehy A, Buettner R, Proia D, Kowolik CM,
Xin H, Armstrong B, Bebernitz G, Weng S, Wang L, Ye M, McEachern K, Chen R, Morosini D, Ioannidis S,
McCoon P, Cao ZA, Yu H, Jove R* & Zinda M*. 2009. The novel JAK2 Inhibitor, AZD1480, potently blocks
Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 16(6):487-97. PMID: 19962667. (*
corresponding authors). (work performed in Dr Jove lab, drug in clinical trial now)
Yu H*, Pardoll D* and Jove* R. STATs in Cancer Inflammation and Immunity: a Leading Role of Stat3.
Nature Reviews Cancer. 9(11):798-809. PMID: 19851315. *corresponding authors. Featured Article.
Kortylewski M, Swiderski P, Herrmann A, Kujawski, M, Wang L, Deng J, Kowolik C, Lee H, Soifer H,
Forman S, Rossi J, Pardoll D, Jove R and Yu H. 2009. In vivo delivery of siRNA to immune cells by
conjugation to a TLR9 agonist enhances antitumor immune responses. Nature Biotechnology, 27(10)
925-932. PMID: 19749770. Featured/Cover article.
Wang L, Yi TS, Pardoll D, Zeng DF and Yu H. 2009. IL-17 can promote tumor growth through an IL6/Stat3 signaling pathway. Journal of Experimental Medicine. 6206(7):1457-646.
Lee HY, Deng JH, Herrmann A, Niu GL, Xin H, Li Z-W, Kujawski M, Forman S, Jove R, Pardoll D and Yu H.
2009. Persistently-activated Stat3 maintains NF-B constitutive activity in tumors. Cancer Cell. 15(4):28393. PMID: 19345327
Kortylewski M, Kujawski M, Herrmann A, Wang L, and Yu H. 2009. Stat3 constrains the efficacies of
TLR9 agonist-based immunotherapy. Cancer Research. 69(6):2497-2505. PMID: 19258507
Xin H, Du Y, Herrmann A, Figlin R and Yu H. 2009. Stat3 inhibition by sunitinib induces apoptosis of renal
cell carcinoma cells and reduces immunosuppressive cells. Cancer Research. 69(6):2506-13. PMID:
19244102
Kortylewski M, Xin H, Kujawski M, Lee H-Y, Liu Y, Harris T, Drake C, Pardoll D and Yu H. 2009.
Regulation of the IL-23/IL-12 balance by Stat3 signaling in the tumor microenvironment. Cancer Cell. 15:
114-123. PMID: 19185846
Kujawski M, Kortylewski M, Lee H.Y, Herrmann A, Kay H, and Yu H. 2008. Stat3 mediates myeloid-celldependent tumor angiogenesis in mice. Journal of Clinical Investigation. 118(10):3367-77. PMID:
18776941.
Kortylewski M and H Yu. 2008. Role of Stat3 in suppressing anti-tumor immunity. Current Opinion in
Immunology. 20(2):228-33. PMID: 18479894
Yu* H, Kortylewski M and Pardoll D. 2007. Crosstalk between cancer and immune cells: the role of STAT3 in
the tumor microenvironment. Nature Reviews Immunology. 7:41-51. *Correspondent author
Kortylewski M, Kujawski M, Wang T-H, Wei S, Zhang S, Pilon-Thomas S, Niu G-L, Kay H, Kerr WG, Mule J,
Jove R, Pardoll D and Yu H. 2005. Inhibiting Stat-3 signaling in the hematopoietic system elicits
multicomponent therapeutic antitumor immune responses. Nature Medicine. 11(12):1314-21.
Yu* H and Jove* R. 2004. The Stats of Cancer – New Molecular Targets Come of Age. Nature Reviews
Cancer, 4: 97-105. *Co-correspondent authors
Wang T-H, Niu G-L, Kortylewski M, Burdelya L, Shain K, Zhang S-M, Bhattacharya R, Gabrilovich D,
Heller R, Coppola D, Dalton D, Jove R, Pardoll D and Yu H. 2004. Regulation of the innate and adaptive
immune responses by Stat3 signaling in tumor cells. Nature Medicine 10:48-54.
Yu H, Porton B, Shen L-Y, Eckhardt LA. 1989. Role of the octamer motif in hybrid cell extinction of
immunoglobulin gene expression: extinction is dominant in a two enhancer system. Cell 58:441-448.
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Principal Investigator/Program Director (Last, First, Middle):
Yu, Hua, Eleanor
C. Research Support
Ongoing Research Support
R01 CA122976-01 Yu (PI)
7/01/2006 – 6/30/2011
NIH/NCI
Role of Stat3 in tumor immune evasion and immune suppression
The major goal of this project is to determine the molecular mechanisms by which Stat3 signaling in regulatory
T cells and CD8+ T cells affects tumor immunity.
R01 CA115815-01 Yu (PI)
9/27/2006 - 8/31/2011
NIH/NCI
Role of Stat3 in modulating tumor microenvironment and angiogenesis
The major goal of this project is to define whether Stat3 is an effective target for modulating tumor
microenvironment and inhibiting angiogenesis.
R01CA146092-01 Yu (PI)
7/1/2009-6/30/2014
NIH/NCI
Target Stat3 for Immunotherapy
The major goal of this project is to target Stat3 to enhance T cell therapy.
ThinkCure
Yu (PI, City of Hope Team), R. Seeger (PI, Children Hospital LA team)
7/1/2009 -6/30/2011
STAT3 targeted therapy for high risk neuroblastoma
R01 CA115674-01 Jove (PI)
5/1/2007 – 2/19/2012
NIH/NCI,
Inhibitors of Src Signaling for Antitumor Therapy
The major goal of this project is to investigate the mechanisms of action of Src kinase inhibitors and identify
gene expression patterns that predict response to therapy.
Role: Co-PI
5 P50 CA107399 (Forman)
09/02/011 – 06/30/16
National Cancer Institute
City of Hope Lymphoma SPORE
The overall goal of this SPORE is to develop translational studies to improve the detection and therapy of
Hodgkin’s and non-Hodgkin’s Lymphoma.
Receiving outstanding scores
Role: Project leader (Project 4)
W. M. Keck Foundation Grant, Forman (PI)
1/1/2008 – 12/31/2010
Antibody-Directed polymeric particles, small interfering ribonucleic Acids (siRNAs) and imaging techniques for
the study of lymphoma.
Role: Key Collaborator
P01 CA43904-16A1 Raubitschek, A (PI)
8/13/2007 – 6/30/2012
NIH
Antibody Targeted Radiation and Immunotherapy for the Treatment of Solid Tumors
Role: Key Collaborator
K12CA01727 Figlin (PI)
7/01/1992 – 11/16/2014
NIH
City of Hope Clinical Oncology Research Development Program
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Principal Investigator/Program Director (Last, First, Middle):
Yu, Hua, Eleanor
Overall goals: The major goal of this project is to provide a total of four years of advanced training in oncologic
clinical investigation to oncologic surgeons, medical oncologists, hematologists, radiation oncologists, or
pathologists at the junior faculty level.
Role: Mentor
R21 CA131765 Badie, B (PI)
6/01/2009 – 5/31/2011
NIH
Carbon Nanotubes for Macrophage Activation in Brain Tumor Models
Overall goals: The goals of this project are to investigate novel immunotherapy approach based on CNTmediated siRNA delivery that can be used for MG/MP activation and ultimately be translated into human
applications for the treatment of both primary and metastatic brain tumors.
Role: Co-PI
Completed funding within Last Three Years
R01 CA100878 Yu (PI)
2/21/2003 – 1/31/2008
NIH/NCI
Stat3 and anti-VEGF therapy in cancer
Role: PI
R01 CA89693 Yu, H (PI)
7/1/2001 – 8/31/2007
NIH/NCI
Immune responses in cancer therapy
Role: PI
Private Foundation Yu (PI)
6/1/2006 – 5/31/2008
Harry J. Lloyd Charitable Trust
Targeting Stat3 to improve melanoma Immunotherapies
Role: PI
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