CURRENT RESEARCH INTERESTS
Hematopoiesis, cancer and stem cells, Wnt
signaling, biomarker discovery, systems biology.
RESEARCH DESCRIPTION
Dr.
Tian directs the cancer and stem cell biology group at the Institute
for Systems Biology (ISB) employing systems approach—with the
empowering genomic, proteomic, and computational strategies—to the
interrogation of both normal and malignant developmental processes.
The goal is to uncover novel stem cell and cancer markers and
mechanisms governing stem cell self-renewal vs. differentiation. Dr.
Tian has successfully applied state of the art high throughput
sequencing, DNA microarray, and mass spectrometry (MS) based
quantitative proteomic approaches for the molecular dissection of
various developmental stages of hematopoietic stem cells (HSC),
embryonic stem cells (ESC), and more recently cancer stem cells
isolated from leukemia and brain tumor patients.
The second area of
research focuses on a key signal transduction pathway—the Wnt/b-catenin
pathway—in the context of stem cell development and tumorigenesis.
The protein-protein interaction network therein has been elucidated by
using sophisticated proteomic approaches; novel b-catenin
interacting partners and phosphorylation events (e.g. Ser552 by Akt)
have been identified, leading to an intriguing new paradigm for b-catenin stabilization with potential clinical applications
targeting cancer stem cells. Functional characterizations of novel
pathway components are being actively pursued in model organisms using
zebra fish and mouse genetics.
The third area of
research concerns blood molecular fingerprints for early disease
diagnosis. Building upon our extensive collection of deep
transcriptomic data from a variety of mouse and human tissues, a panel
of tissue-specific, secreted proteins can be selected for each organ,
with peptides representing each proteins synthesized. Since blood
serves as a window for diseases and the state of progression of these
diseases, a MS-based proteomic strategy using this panel of molecular
fingerprints can be applied to examine cancer patient blood samples
for the identification of blood biomarkers that can be used for early
detection and stratification of cancer.
All
these research efforts are cultivated in an interdisciplinary team
environment leveraging supports from several NIH center/program
project grants in close collaboration with leaders in systems biology
(Dr. Leroy Hood), stem cell biology (Drs. Irving Weissman and Michael
Clarke, Stanford; Dr. Linheng Li, Stowers), neuro-oncology (Dr. Greg
Foltz, Swedish Hospital), and nanotechnology (Dr. Jim Heath, Caltech).
Expertise and knowledge gained from these studies are readily
applicable to other biological and disease systems as exemplified by
several ongoing and planned collaborations in the Division and UW-ISCRM
(Reems, Blau, Ware, Moon, and Abkowitz).
SELECTED PUBLICATIONS
Yan
X, Ma L, Yi D, Yoon JG, Diercks A, Foltz G, Price ND, Hood LE, Tian Q. A
CD133-related gene expression signature identifies an aggressive
glioblastoma subtype with excessive mutations. Proc
Natl Acad Sci U S A. 2011 Jan 10. [Epub ahead of print]
Tu LC, Foltz G, Lin E, Hood L, Tian
Q. Targeting stem cells-clinical implications for cancer
therapy. Curr
Stem Cell Res Ther. 4(2):147-5,
(2009)
Majeti
R§, Becker MW§, Tian
Q§, Lee TL, Yan X, Liu R, Chiang JH, Hood L, Clarke
MF, Weissman IL. Dysregulated
gene expression networks in human acute myelogenous leukemia stem
cells. Proc
Natl Acad Sci U S A. 2009,
106(9):3396-401. (§equal contribution)
Ghosh D, Yan X, Tian Q. Gene regulatory networks in embryonic stem cells and brain
development. Birth
Defects Res C Embryo Today. 87(2):182-91, 2009
Reynolds JM, Pappu BP, Peng J, Martinez
GJ, Zhang Y, Chung Y, Ma L, Yang XO, Nurieva RI, Tian Q, Dong
C. Toll-like
receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17
responses and regulates the pathogenesis of autoimmune disease.
Immunity.
32(5):692-702,
2010.
Epub 2010 Apr 29
Chung
Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich
SS, Jetten AM, Tian Q, Dong
C. Critical regulation of
early Th17 cell differentiation by interleukin-1 signaling. Immunity. 30(4):576-87, 2009. Epub 2009 Apr 9
Liu
X, Alexiou M, Martin-Orozco N, Chung Y, Nurieva RI, Ma L, Tian Q, Kollias G, Lu S, Graf D, Dong C.
Cutting edge: A critical role of B and T lymphocyte attenuator
in peripheral T cell tolerance induction. J Immunol. 182(8):4516-20,
2009
Yamazaki
T, Yang XO, Chung Y, Fukunaga A, Nurieva R, Pappu B, Martin-Orozco N,
Kang HS, Ma L, Panopoulos AD, Craig S, Watowich SS, Jetten AM, Tian Q, Dong C. CCR6
regulates the migration of inflammatory and regulatory T cells. J Immunol. 181(12):8391-401, 2008
Nurieva
RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L, Wang YH, Watowich SS,
Jetten AM, Tian Q, Dong C. Generation
of T follicular helper cells is mediated by interleukin-21 but
independent of T helper 1, 2, or 17 cell lineages. Immunity.
29(1):138-49,
2008.
Epub 2008 Jul 3
Price ND, Foltz G, Madan A, Hood L, and Tian
Q. Systems Biology and Cancer Stem Cells. J
Cell Mol Med. Nov 20,
2007. [Epub ahead of
print].
Hu, Z., Hood, L., and Tian Q. Quantitative proteomic approaches for biomarker
discovery. Proteomics Clin. Appl. 1,
1036-1041,
2007
Ma L, Sun B, Hood L, and Tian
Q. Molecular profiling of stem cells. Clinica
chimica acta; international journal of clinical chemistry 378, 24-32, 2007
Tian
Q, Stepaniants SB, Mao M, Weng L, Feetham MC, Doyle MJ,
Yi EC, Dai H, Thorsson V, Eng J, et al. Integrated genomic and proteomic analyses of gene expression in Mammalian cells.
Mol Cell Proteomics
3, 960-969, 2004 Park IK, He Y, Lin F, Laerum OD, Tian
Q, Bumgarner R, Klug CA, Li K, Kuhr C, Doyle MJ, et al. Differential gene expression profiling of adult murine hematopoietic
stem cells. Blood
99, 488-498, 2002 Tian
Q. Proteomic exploration of the Wnt/beta-catenin
pathway. Current opinion in molecular
therapeutics 8, 191-197,
2006 Tian
Q, Feetham MC, Tao WA, He XC, Li L,
Aebersold R, and Hood L. Proteomic analysis identifies that
14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt. Proc.
Natl. Acad. Sci. USA 101, 15370-15375, 2004 He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville
DH, Tian Q,
Zeng X, He X, Wiedemann LM, et al. BMP signaling inhibits
intestinal stem cell self-renewal through suppression of Wnt-beta-catenin
signaling. Nature genetics
36, 1117-1121, 2004 Tian
Q, He XC, Hood L, and Li L. Bridging the
BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta. Cell Cycle 4(2), 215-216,
2005 He XC, Yin T, Grindley JC, Tian
Q, Sato T, Tao WA, Dirisina R, Porter-Westpfahl KS, Hembree M, Johnson T, et al.
PTEN-deficient intestinal stem cells initiate
intestinal polyposis. Nature genetics 39, 189-198, 2007 Yang XO, Pappu BP, Nurieva R, Akimzhanov A, Kang
HS, Chung Y, Ma L, Shah B, Panopoulos AD, Schluns KS,
Watowich SS, Tian Q,
Jetten AM, and Dong C. T helper 17 lineage differentiation is
programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity
28, 29-39, 2008 Nurieva R, Yang XO, Martinez G, Zhang Y,
Panopoulos AD, Ma L, Schluns K, Tian
Q, Watowich SS, Jetten AM and Dong C. Essential autocrine
regulation by IL-21 in the generation of inflammatory T cells. Nature
448, 480-483, 2007 Park H, Li Z, Yang XO, Chang SH,
Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, and Dong C. A distinct lineage of CD4 T cells
regulates tissue inflammation by producing interleukin 17. Nature immunology 6,
1133-1141, 2005
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