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Qualifications:
- M.D., Ph.D.
Expertise/
Research Interests:
A major interest of our laboratory is to study the genetic alterations
and their molecular mechanisms in human ovarian cancer. Specifically,
we are interested in elucidation of normal cellular function of the PI3K/Akt
and Aurora-A pathways and to characterize their role in human ovarian
carcinogenesis. In particular, we are focusing on the identification of
molecules that are specifically regulated by Akt or Aurora-A as well as
the molecules that are regulated by PI3K/PTEN but not Akt. In addition,
we are also interested in the identification of small molecule inhibitors
of Akt and Aurora-A for cancer intervention. The underlying hypothesis
of these researches is that Akt and Aurora-A contribute to the control
of ovarian surface epithelial cell proliferation and malignant transformation
by mediating important signals. Thus, Akt and Aurora-A could be critical
targets for therapeutic intervention of human ovarian cancer. We have
previously demonstrated frequent alterations of Akt and Aurora-A in human
ovarian cancer and identified a number of molecules that are regulated
by Akt or Aurora-A. We have also identified several chemical compounds
that specifically inhibit Akt or Aurora-A, one of which is currently in
clinic trial. In addition, our laboratory have characterized the promoters
of Akt and Aurora-A, and demonstrated transcriptional regulation of Akt
and Aurora-A by a number of oncogenic transcriptional factors.
Memberships:
- American Association for Advancement of Science
- American Association for Cancer Research
- American Society for Microbiology
- American Society for Biochemistry and Molecular Biology
Previous
Positions:
- 2005-present, Professor, University
of South Florida College of Medicine, Tampa, FL.
- 2001-2005, Associate Professor,
University of South Florida College of Medicine, Tampa, FL.
- 1997-2001, Assistant Professor,
University of South Florida College of Medicine, Tampa, FL.
- 1996-1997, Staff Scientist, Fox
Chase Cancer Center, Philadelphia, PA.
- 1994-1996, Senior Research Associate,
Fox Chase Cancer Center, Philadelphia, PA.
- 1990-1994, Postdoctoral Fellow,
Fox Chase Cancer Center, Philadelphia; Graduate Student, Paris-XIII University,
Paris, France.
- 1988-1990, Graduate Student, Paris-XIII
University, Paris, France.
- 1986-1988, Attending Doctor, Beijing Thoracic Tumor
Institute, Beijing, China.
Publications:
- Lee
H, Dan HC, Kim D, Cao C, Nicosia SV, Golemis EA, Liu W, Testa JR, Cheng
JQ. Identification and characterization of putative tumor suppressor
NGB, a GTP-binding protein that interacts with the neurofibromatosis
2 protein. In press in Mol. Cell. Biol.
- Yang H, He L, Kruk P, Nicosia
SV, Cheng JQ. Aurora-A Induces Cell Survival and Chemoresistance
by Activation of Akt through a p53-dependent Manner in Ovarian Cancer
Cells. In press in Int. J. Cancer
- Pu P, Kang C, Li J, Jiang H,
Cheng J. The Effects of Antisense AKT2 RNA on the Inhibition
of Malignant Glioma Cell Growth in vitro and in vivo. J. Neurooncol.
76:1-11, 2006.
- Wang G, Barrett JW, Stanford
M, Gao X, Sun M, Cheng JQ, McFadden G. Permissive infection of
human cancer cells with mxyoma virus requires activation of Akt via
interaction with a viral homolog of PIKE-A Proc Natl Acad Sci USA 103:4640-5,
2006.
- Gritsko T, Williams A, Turkson
J, Kaneko S, Bowman T, Huang M, Nam S, Eweis I, Diaz N, Sullivan D,
Yoder S, Enkemann S, Eschrich S, Lee JH, Beam CA, Cheng J, Minton
S, Muro-Cacho CA, Jove R. Persistent activation of stat3 signaling induces
survivin gene expression and confers resistance to apoptosis in human
breast cancer cells. Clin Cancer Res. 12:11-19, 2006.
- Fang Q, Naidu KA, Naidu KA,
Zhao H, Sun M, Dan HC, Nasir A, Kaiser HE, Cheng JQ, Nicosia
SV, Coppola D. Ascorbyl stearate inhibits cell proliferation and tumor
growth in human ovarian carcinoma cells by targeting the PI3K/AKT pathway.
Anticancer Res. 26:203-209, 2006.
- Park S, Kim D, Szewczyk K.M,
Nicosia S.V, Yu H, Jove R, Cheng JQ. Molecular cloning and characterization
of the human Akt1 promoter uncovers its upregulation by the Src/Stat3
pathway. J Biol Chem 280:38932-38941 2005.
- Niesen MI, Osborne AR, Yang
H, Rastogi S, Chellappan S, Cheng JQ, Boss JM, Blanck G. Activation
of a methylated promoter mediated by a sequence specific DNA binding
protein: RFX. J Biol Chem. 280:38914-38922, 2005.
- Kim D, Cheng GZ, Lindsley CW,
Yang H, Cheng JQ. Targeting the phosphatidylinositol-3 kinase/Akt
pathway for the treatment of cancer. Current Opinion in Invest. Drugs,
6:120-1258, 2005.
- Nam S, Kim D, Cheng JQ,
Zhang S, Lee JH, Buettner R, Mirosevich J, Lee FY, Jove R. Action of
the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate
cancer cells.
Cancer Res. 65:9185-9189, 2005.
- Cheng JQ*, Lindsley CW,
Cheng GZ, Yang H, Nicosia SV. The Akt/PKB pathway: molecular target
for cancer drug discovery. Oncogene 245:7482-7492, 2005 (* Corresponding
author)
- Xu Q, Briggs J, Park S, Niu
G, Kortylewski M, Zhang S, Gritsko T, Turkson J, Kay H, Semenza GL,
Cheng JQ*, Jove R, Yu H*. Targeting Stat3 blocks both HIF-1 and
VEGF expression induced by multiple oncogenic growth signaling pathways.
Oncogene. 24:5552-5560 2005 (*Co-corresponding author)
- Nam S, Buettner R, Turkson J,
Kim D, Cheng JQ, Muehlbeyer S, Hippe F, Vatter S, Merz KH, Eisenbrand
G, Jove R. Indirubin derivatives inhibit Stat3 signaling and induce
apoptosis in human cancer cells. Proc Natl Acad Sci USA. 102:5998-6003,
2005.
- Yuan ZQ, Kim D, Kaneko S, Sussman
M, Bokoch GM, Kruh GD, Nicosia SV, Testa JR, Cheng JQ. ArgBP2g
interacts with Akt and p21-activated kinase-1 and promotes cell survival.
J Biol Chem. 280:21483-21490, 2005.
- Patel NA, Kaneko S, Apostolatos
HS, Bae SS, Watson JE, Davidowitz K, Chappell DS, Birnbaum MJ, Cheng
JQ, Cooper DR. Molecular and genetic studies imply Akt-mediated
signaling promotes PKCbII alternative splicing via phosphorylation of
SRp40. J Biol Chem. 280:14302-14309, 2005
- Kim D, Dan HC, Park S, Yang
L, Liu Q, Kaneko S, Ning J, He L, Yang H, Sun M, Nicosia SV, Cheng
JQ. AKT/PKB signaling mechanisms in cancer and chemoresistance.
Front Biosci. 10:975-784, 2005.
- Liu, Q., Kaneko, S., Yang, L.,
Feldman, R.I., Nicosia, S.V., Chen, J.D., and Cheng, J.Q. Aurora-A
abrogates p53 DNA-binding and transactivation activity by phosphorylation
of serine-215. J. Biol. Chem. 279:52175-52182, 2004.
- Yang, L., Dan, H.C., Sun, M.,
Liu, Q., Sun, X., Feldman, R.I., Hamilton, A.D., Polokoff, M., Nicosia,
S.V., Herlyn, M., Sebti, S.M., and Cheng, JQ. Akt/Protein kinase
B signaling inhibitor-2, a selective small molecule inhibitor of Akt
signaling with antitumor activity in cancer cells overexpressing Akt..
Cancer Res. 64:4394-4399, 2004.
- Johnson N.C., Dan, H.C., Cheng,
J.Q., and Kruk, P.A. BRCA1 185delAG mutation inhibits Akt-dependent,
IAP-mediated caspase 3 inactivation. Exp. Cell Res. 298:9-16, 2004.
- Stahl, J.M., Sharma, A., Cheung,
M., Zimmerman, M., Cheng, J.Q., Bosenberg, M.W., Kester, M.,
Sandirasegarane, L., and Roberson, G.P. Deregulation of Akt3 activity
promotes development of malignant melanoma. Cancer Res. 64:7002-7010,
2004.
- Dufour G, Demers MJ, Gagne D,
Dydensborg AB, Teller IC, Bouchard V, Degongre I, Beaulieu JF, Cheng
JQ, Fujita N, Tsuruo T, Vallee K, Vachon PH. Human intestinal epithelial
cell survival and anoikis. Differentiation state-distinct regulation
and roles of protein kinase B/Akt isoforms.
J Biol Chem. 279:44113-44122, 2004.
- Jiang K., Sun J., Cheng J.,
Djeu J.Y, Wei, S., and Sebti S.M. Akt mediates Ras downregulation of
RhoB, a suppressor of transformation, invasion, and metastasis. Mol.
Cell. Biol. 24:5565-5576, 2004.
- Dan C, Sun M, Kaneko S, Feldman
RI, Nicosia SV, Wang H-G, Tsang BK, Cheng JQ. Akt Phosphorylation
and Stabilization of XIAP in Human Ovarian Cancer Cells. J. Biol. Chem.
279:5405-5412, 2004.
- Yang, H., Ou, C., Feldman, FI.,
Nicosia, SV. Kruk, PA., and Cheng, JQ. Aurora-A Aurora-A regulates
telomerase activity through c-Myc in human ovarian and breast epithelial
cells. Cancer Res. 64:463-467, 2004.
- Dan HC, Coppola D, Jinag K,
Liu A, Hamilton AD, Nicosia SV, Sebti SM, Cheng JQ. Phosphatidylinositol-3-OH
Kinase/Akt and Survivin Pathways as Critical Targets for Geranylgeranyltransferase
I Inhibitors Induced Apoptosis. Oncogene, 23:706-715, 2004.
- Nicosia, S.V., Willbanks, G.D.,
Saunders, B., Mayer, J., Cardosi, R.J., Kruk, P.A., Cheng, J.Q.,
Bai, W., Coppola, D., and Fiorica, J.V. Cytology of Human Ovarian Surface
Epithelial Brushings. Cancer Cytopath. 102:1-10, 2004.
- Leung BM, Fraser M, Yan X, Dan
HC, Cheng JQ, Tsang BK. p53 is a determinant of X-linked inhibitor
of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer
cells. Cancer Res., 63:7081-7088, 2003.
- Sekharam M, Zhao H, Sun M, Fang
Q, Zhang Q, Yuan Z, Dan HC, Boulware D, Cheng JQ, Coppola D.
Insulin-like growth factor 1 receptor enhances invasion and induces
resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L)
pathway. Cancer Res. 63:7708-7716, 2003.
- Sun M, Yang L, Feldman RI, Sun
X, Jove R, Nicosia SV, Cheng JQ. Activation of Phosphatidylinositol-3-OH
Kinase/Akt Pathway by Androgen through interaction of p85a, AR and Src.
J. Biol. Chem. 278:42992-3000, 2003.
- Iravani S, Zhang HQ, Yuan ZQ,
Cheng JQ, Karl RC, Jove R, Coppola D. Modification of insulin-like
growth factor 1 receptor, c-Src, and Bcl-XL protein expression during
the progression of barrett's neoplasia. Hum Pathol. 34:975-982, 2003.
- Nicosia SV, Bai W, Cheng
JQ, Coppola D, Kruk PA. Oncogenic pathways implicated in ovarian
epithelial cancer. Hematol Oncol Clin North Am. 17:927-943, 2003.
- Chen T, Yang I, Irby R, Shain
KH, Wang HG, Quackenbush J, Coppola D, Cheng JQ, and Yeatman
TJ. Regulation of caspase expression and apoptosis by adenomatous polyposis
coli. Cancer Res. 63:4368-4374, 2003.
- Yuan Z, Feldman RI, Sussman
GE, Coppola D, Nicosia SV, and Cheng JQ. AKT2 inhibition of cisplatin-induced
JNK/p38 and Bax activation by phosphorylation of ASK1: Implication of
AKT2 in chemoresistance. J. Biol. Chem. 278:23432-13440, 2003.
- Gritsko TM, Coppola D, Paciga
JE, Yang L, Sun M, Shelley SA, Fiorica JV, Nicosia SV, Cheng JQ.
Activation and overexpression of centrosome kinase BTAK/Aurora-A in
human ovarian cancer. Clin Cancer Res. 9:1420-1426, 2003.
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