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Robert Glazer Professor of Oncology |
One focus of our research is the role of the nuclear receptor, peroxisome proliferator-activated receptord (PPARd), a ligand-dependent transcription factor involved in oxidative metabolism and tumorigenesis. We have established a transgenic mouse model expressing PPARd in the mammary gland, which upon ligand activation rapidly elicits ductal adenocarcinomas. We are currently examining the unique oncogenic and metabolomic signaling pathways in this model and in tumor cell lines generated from these mice. We have also established a PPARd-dependent gastric cancer model that is sensitive to a PPARd suicide inhibitor under development in collaboration with the Drug Discovery Program.
A second area of study concerns the role of stem cell antigen-1 (Sca-1) in mammary tumorigenesis. Sca-1 was the first marker of stem and early progenitor cells discovered more than 20 years ago, but whose function has remained a mystery. We have found that Sca-1 inhibits the expression of TGF-b signaling through a unique signaling pathway that activates Smad3. Loss of Sca-1 also reactivates other tumor suppressor genes, such as PTEN and PPAR(gamma).
Thus, our current research focuses on the inter-relationships between oncogenic and stem cell pathways, and their roles in modulating tumorigenesis.
Selected Publications:
Yuan H, Kopelovich L, Yin Y, Lu J, Glazer RI. Drug-Targeted Inhibition of Peroxisome Proliferator-Activated Receptor-gamma Enhances the Chemopreventive Effect of Anti-Estrogen Therapy. Oncotarget. 2012.
Yuan H, Upadhyay G, Lu J, Kopelovich L, Glazer RI. The Chemopreventive Effect of Mifepristone on Mammary Tumorigenesis is Associated with an Anti-invasive and Anti-inflammatory Gene Signature. Cancer Prev Res (Phila). 2012.
Glazer RI, Vo DT, Penalva LO.
Musashi1: an RBP with versatile
functions in normal and cancer stem cells.
Front Biosci. 17:54-64. 2012
Yuan H, Upadhyay G, Yin Y, Kopelovich L,
Glazer RI.
Stem Cell Antigen-1 Deficiency Enhances the Chemopreventive
Effect of Peroxisome Proliferator-Activated Receptor{gamma}
Activation. Cancer Prev Res
(Phila). 2011
Ringer L, Sirajuddin P, Heckler
M, Ghosh A, Suprynowicz F, Yenugonda VM, Brown ML, Toretsky
JA, Uren A, Lee Y, Macdonald TJ, Rodriguez O, Glazer RI,
Schlegel R, Albanese C.
VMY-1-103 is a novel CDK inhibitor that disrupts chromosome
organization and delays metaphase progression in
medulloblastoma cells. Cancer Biol
Ther. 12(9):818-26, 2011
Upadhyay, G., Yin, Y., Yuan, H., Li, X., Derynck, R. and
Glazer, R.I.
Stem cell antigen-1 enhances tumorigenicity by disruption of
growth differentiation factor-10 (GDF10)-dependent
TGF-{beta} signaling. Proc. Natl. Acad. Sci. U.S.A., in press, Epub April 25,
2011) Pollock CB, Yin Y, Yuan H, Zeng X, King
S, Li X, Kopelovich L, Albanese C, Glazer RI.
PPAR{delta} activation acts
cooperatively with 3-phosphoinositide-dependent protein
kinase-1 to enhance mammary tumorigenesis.
PLoS One.
6:E16215, Jan 13 2011 Pollock CB, Rodriguez O, Martin PL,
Albanese C, Li X, Kopelovich L, Glazer RI.
Induction of metastatic gastric
cancer by peroxisome proliferator-activated receptor{delta}
activation. PPAR Res. Dec 27 2010 Glazer RI.
A new therapeutic basis for
treating Li-Fraumeni Syndrome breast tumors expressing
mutated TP53. Oncotarget.1:470-1, Nov 2010
Wang XY, Penalva LO, Yuan H, Linnoila RI, Lu J, Okano H,
Glazer RI.
Musashi1 regulates breast tumor cell proliferation and is a
prognostic indicator of poor survival.
Mol Cancer.
9:221, 2010
Li S, Zhang D, Yang L, Burnier JV, Wang N, Lin R, Lee ER,
Glazer RI, Brodt P.
The IGF-I receptor can alter the matrix metalloproteinase
repertoire of tumor cells through transcriptional regulation
of PKC-{alpha}. Mol Endocrinol.
23:2013-25, 2009 Dupasquier S, Abdel-Samad R, Glazer RI, Bastide P, Jay
P, Joubert D, Cavailles V, Blache P, Quittau-Prevostel C.:
A new mechanism of SOX9 action to regulate PKC{alpha}
expression in the intestine epithelium.
J
Cell Sci. 122:2191-6, 2009
Rodriguez OC, Lai EW, Vissapragada S, Cromelin C,
Avetian M, Salinas P, Ramos H, Kallakury B, Casimiro M,
Lisanti MP, Tanowitz HB, Pacak K, Glazer RI, Avantaggiati M,
Albanese C.:
A reduction in Pten tumor suppressor activity promotes
ErbB-2-induced mouse prostate adenocarcinoma formation
through the activation of signaling cascades downstream of
PDK1.
Am J Pathol. 174:2051-60, 2009
Wang X, Zhao J, Tang S, Lee S, Glazer RI, Hewlett I.:
c-FLIPL regulates PKC via AP-2 to inhibit Bax-mediated
apoptosis induced by HIV-1 gp120 in Jurkat cells.
Mol Cell Biochem. 2009 Apr 11 Yin Y, Yuan H, Zeng X, Kopelovich L, Glazer RI.:
Inhibition of peroxisome proliferator-activated receptor
gamma increases estrogen receptor-dependent tumor
specification.
Cancer Res.
69:687-94, 2009 Glazer RI, Wang XY, Yuan H, Yin Y.:
Musashi1: a stem cell marker no longer in search of a
function.
Cell Cycle. 7:2635-9, 2008 Glazer RI, Yuan H, Xie Z, Yin Y.:
PPARgamma and PPARdelta as Modulators of Neoplasia and Cell
Fate.
PPAR Res.
2008:247379, 2008 Wang XY, Yin Y, Yuan H, Sakamaki T, Okano H, Glazer RI:
Musashi1 modulates mammary progenitor cell expansion through
proliferin-mediated activation of the Wnt and Notch
pathways.
Mol Cell Biol. 28:3589-99,
2008 Glazer RI, Wang X, Yuan H, Yin Y:
Mammary stem and progenitor cell regulation.
Cancer Biomark. 3:171-81, 2007 Smee DF, Hurst BL, Wong MH, Glazer RI,
Rahman A, Sidwell RW.:
Efficacy of N-methanocarbathymidine in treating mice
infected intranasally with the IHD and WR strains of
vaccinia virus.
Antiviral Res. 76:124-9, 2007 Herschkowitz JI, Simin K, Weigman VJ,
Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia
S, Chandrasekharan S, Backlund MG, Yin Y, Khramtsov AI,
Bastein R, Quackenbush J, Glazer RI, Brown PH, Green JE,
Kopelovich L, Furth PA, Palazzo JP, Olopade OI, Bernard PS,
Churchill GA, Van Dyke T, Perou CM.:
Identification of conserved gene expression features between
murine mammary carcinoma models and human breast tumors.
Genome Biol. 8:R76, 2007 Liang K, Lu Y, Li X, Zeng X, Glazer RI,
Mills GB, Fan Z.:
Differential roles of phosphoinositide-dependent protein
kinase-1 and akt1 expression and phosphorylation in breast
cancer cell resistance to Paclitaxel, Doxorubicin, and
gemcitabine.
Mol Pharmacol.70:1045-52, 2006 Xie Z, Yuan H, Yin Y, Zeng X, Bai R,
Glazer RI.:
3-phosphoinositide-dependent protein kinase-1 (PDK1)
promotes invasion and activation of matrix
metalloproteinases.
BMC Cancer. 21;6:77, 2006 Yin Y, Yuan H, Wang C, Pattabiraman N, Rao
M, Pestell RG, Glazer RI.:
3-phosphoinositide-dependent protein kinase-1 activates the
peroxisome proliferator-activated receptor-gamma and
promotes adipocyte differentiation.
Mol Endocrinol. 20:268-78, 2006 Click here to do a Medline Search for all publications of
Robert Glazer.
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