Robert Glazer

Professor of Oncology

Ph.D., Pharmacology
Indiana University, 1970
(202) 687-8324
glazerr@georgetown.edu

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:

• Glazer RI. PPARδ as a Metabolic Initiator of Mammary Neoplasia and Immune Tolerance.PPAR Res.3082340, 2016.
• Zhou X, Zhu W, Nowicki M, Miao S, Cui H, Holmes B, Glazer RI, Zhang LG. 3D Bioprinting a Cell-Laden Bone Matrix for Breast Cancer Metastasis Study.ACS Appl Mater Interfaces.[Epub ahead of print], 2016.
• Zhu W, Castro NJ, Cui H, Zhou X, Boualam B, McGrane R, Glazer RI, Zhang LG. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions. Nanotechnology. 27(31):315103. [Epub ahead of print],2016.
• Zhu W, Holmes B, Glazer RI, Zhang LG. 3D printed nanocomposite matrix for the study of breast cancer bone metastasis. Nanomedicine. 12(1):69-79, 2016. doi: 10.1016/j.nano.2015.09.010. Epub, 2015.
• Bernstein DI, Bravo FJ, Pullum DA, Shen H, Wang M, Rahman A, Glazer RI, Cardin RD. Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs. Antivir Chem Chemother. 24(1):19-27, 2015.
• Ligaba SB, Khurana A, Graham G, Krawczyk E, Jablonski S, Petricoin EF, Glazer RI, Upadhyay G. Multifactorial analysis of conditional reprogramming of human keratinocytes. PLoS One. 10(2):e0116755. doi: 10.1371/journal.pone.0116755. eCollection, 2015.
• Yuan H, Lu J, Xiao J, Upadhyay G, Umans R, Kallakury B, Yin Y, Fant ME, Kopelovich L, Glazer RI. PPARδ induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTOR activation. Cancer Res. 2013 Jul 15;73(14):4349-61
• Wang XY, Yu H, Linnoila RI, Li L, Li D, Mo B, Okano H, Penalva LO, Glazer RI. Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. Oncotarget. 2013 May;4(5):739-50.
• 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 Mar;3(3):345-56.
• 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
• Koller E, Propp S, Zhang H, Zhao C, Xiao X, Chang M, Hirsch SA, Shepard PJ, Koo S, Murphy C, Glazer RI, Dean NM.: Use of a chemically modified antisense oligonucleotide library to identify and validate Eg5 (kinesin-like 1) as a target for antineoplastic drug development. Cancer Res. 66:2059-66, 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
• Zhan M, Yu D, Liu J, Glazer RI, Hannay J, Pollock RE.: Transcriptional repression of protein kinase Calpha via Sp1 by wild type p53 is involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation. J Biol Chem. 280:4825-33, 2005
• Yin Y, Bai R, Russell RG, Beildeck ME, Xie Z, Kopelovich L, Glazer RI.: Characterization of medroxyprogesterone and DMBA-induced multilineage mammary tumors by gene expression profiling. Mol Carcinog. 44:42-50, 2005
• Yin Y, Russell RG, Dettin LE, Bai R, Wei ZL, Kozikowski AP, Kopelovich L, Glazer RI.: Peroxisome proliferator-activated receptor delta and gamma agonists differentially alter tumor differentiation and progression during mammary carcinogenesis. Cancer Res. 65:3950-7, 2005
• Wei ZL, Petukhov PA, Bizik F, Teixeira JC, Mercola M, Volpe EA, Glazer RI, Willson TM, Kozikowski AP.: Isoxazolyl-serine-based agonists of peroxisome proliferator-activated receptor: design, synthesis, and effects on cardiomyocyte differentiation. J Am Chem Soc.126:16714-5.
• Xie Z, Zeng X, Waldman T, Glazer RI.: Transformation of mammary epithelial cells by 3-phosphoinositide- dependent protein kinase-1 activates beta-catenin and c-Myc, and down-regulates caveolin-1. Cancer Res. 63:5370-5, 2003
• Kopelovich L, Fay JR, Glazer RI, Crowell JA.: Peroxisome proliferator-activated receptor modulators as potential chemopreventive agents. Mol Cancer Ther. 1:357-63, 2002
• Clark JH, Haridasse V, Glazer RI.: Modulation of the human protein kinase C alpha gene promoter by activator protein-2. Biochemistry. 41:11847-56, 2002
• Ackler S, Ahmad S, Tobias C, Johnson MD, Glazer RI.: Delayed mammary gland involution in MMTV-AKT1 transgenic mice. Oncogene. 21:198-206, 2002
• Zeng X, Xu H, Glazer RI.: Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with the induction of protein kinase Calpha. Cancer Res. 62:3538-43, 2002
• Park BK, Zeng X, Glazer RI.: Akt1 induces extracellular matrix invasion and matrix metalloproteinase-2 activity in mouse mammary epithelial cells. Cancer Res. 61:7647-53, 2001
• Bansal R, Chen HX, Marshall JL, Tan J, Glazer RI, Wainer IW.: Detection of a mixed-backbone oligonucleotide (GEM 231) in liver and tumor tissues by capillary electrophoresis. J Chromatogr B Biomed Sci Appl. 750:129-35, 2001

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