Robert J Schneider, PhD

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Albert Sabin Professor of Microbiology and Molecular Pathogenesis;
Associate Dean for Therapeutics Aliliances.  Depts of Microbiology and Radiation Oncology.
Ph.D., 1985 Mount Sinai School of Medicine

LAB WEBSITE:
Schneider Lab
RESEARCH THEMES:
Cancer Stem Cells, Breast cancer, Inflammation, Control of Protein Synthesis and mRNA Translation, Aging, Tissue Progenitor Cells
KEYWORDS:
Breast Cancer, Cancer Stem Cells, Metastasis, Translational Regulation, mTOR, Mesenchymal Transition

Contact Information

Department of Microbiology
Medical Sciences Building, Room 238
NYU School of Medicine
550 First Avenue
New York, NY 10016
Office Tel: (212) 263-6006
Lab Tel: (212) 263-6007, 6079
Fax:  (212) 263-8276
E-mail: Robert.Schneider@nyumc.org(preferred method of contact)
 


Development, progression and metastasis of breast cancer as controlled by translational regulation.

My lab conducts research in breast cancer at the level of basic, translational and clinical investigation, as well as in developmental therapeutics.  The major focus of my research is directed to the molecular and genetic understanding of advanced breast cancers and metastasis, and the development of new treatment strategies and therapeutics for advanced breast cancer, particularly focused on the role of the breast cancer stem cell and translational regulation. Our research has been instrumental in the development of the small molecule inhibitor of VEGF mRNA translation known as PTC299, in Phase 2 clinical trials at NYU and elsewhere with PTC Therapeutics. We elucidated the importance of mTOR in translational control in breast cancer and its downstream effects on translation factor eIF4G and eIF4E and the translation regulator 4E-BP1 as a major component of locally advanced and inflammatory breast cancer (LABC, IBC), and developed animal models for both. We also showed the importance of mTOR and overexpressed eIF4GI as a major pathological event underlying the development of metastatic progression of IBC and metastasis.  More recently, we have identified the importance of overexpressed translation initiation factors in the development and proliferation of breast cancer stem cells.

My lab also works on the regulation of the inflammatory response. Many of the most powerful biological regulators of cell growth and proliferation are encoded by unstable mRNAs that are targeted for rapid degradation by the cell.  The loss of rapid degradation of these mRNAs can result in a variety of inflammatory cytokine diseases, including septic shock, psoriasis, dermatitis and even oncogenic transformation. Targeted degradation of short-lived inflammatory cytokine and proto-oncogene mRNAs is controlled in a regulated manner by an AU-rich element (ARE) located in the 3' noncoding region, and by several proteins that bind this sequence.  We have shown that the ARE binding protein known as AUF1 is a major regulator of inflammatory cytokine and proto-oncogene mRNA stability.  By development of a mouse deleted of the AUF1 gene, they demonstrated that loss of AUF1 activity may play a role in the development of certain cancers, in the development of psoriasis and other chronic inflammatory diseases, in the development of mature B cells, and in the ability to attenuate the inflammatory response following microbial infection and exposure to ionizing radiation. We are studying the mechanisms by which degradation of short-lived inflammatory cytokine and proto-oncogene mRNAs are regulated by AUF1, the mechanism by which physiological stimuli alter the function of AUF1, the complex of proteins that act on the AU-rich element to control degradation and the diseases caused by knockout of these proteins in mouse model systems.

Selected Publications: 
  • Pola, Carolina; Formenti, Silvia C; Schneider, Robert J. Vitronectin-alphavbeta3 Integrin Engagement Directs Hypoxia-Resistant mTOR Activity and Sustained Protein Synthesis Linked to Invasion by Breast Cancer Cells.  Cancer research 2013 Jul;73(14):4571-4578. PMID: 23722547
  • Arslan, AA; Silvera, D; Arju, R; Giashuddin, S; Belitskaya-Levy, I; Formenti, SC; Schneider, RJ. Atypical ezrin localization as a marker of locally advanced breast cancer.  Breast cancer research & treatment 2012 Mar;:981-988. PMID: 22415480
  • Badura, M., Braunstein, S., Zavadil, J. and Schneider, R.J. (2012).  DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs. Proc. Natl. Acad. Sci. USA 2012 Nov;109(46): 18767-18772. PMID: 23112151
  • Pont, A.R., Sadri, N., Hsiao, S., Smith, S. and Schneider, R.J. (2012).  AUF1 deficiency links chronic inflammation to accelerated aging, senescence and cancer.  Mol. Cell Jul;47(1):5-15. PMID: 22633954
  • Arslan, A.A., Silvera, D., Arju, R., Giashuddin, S., Belitskaya-Levy, I., Formenti, S.C. and Schneider, R.J. (2012).  Atypical ezrin localization as a marker of locally advanced breast cancer.  Breast Cancer Res. Treat.  Aug;134(3):981-8. PMID: 22415480
  • Korets, S., Czok, S., Blank, S. Curtin, J. and Schneider, R.J. (2011). Targeting the mTOR/4E-BP Pathway in Endometrial Cancer. Clinical Cancer Res. 17:7518-7528. PMID: 22142830
  • Wu, X., Chen, F., Sahin, A., Albarracin, Pei, Z., Zou, X., Singh, B., Xu, R., Daniels, G., Li, Y., Wei, J., Blake, M., Schneider, R.J., Cowin, P., Lee, P. (2011). Distinct function of androgen receptor coactivator ARA70alpha and ARA70beta in mammary gland development and breast cancer. Breast Cancer Res. Treat. 28:391-400. PMID: 20814820
  • Adams, S., Bapsi Chakravarthy, A., Donach, M., Spicer, D., Lymberis, S., Singh, B., Bauer, J.A., Hochman, T., Goldberg, J.D., Muggia, F., Schneider, R.J., Pietenpol, J.A., and Formenti, S.C. (2010). Five-Year Results Of Preoperative Paclitaxel With Concurrent Radiation Therapy In Locally Advanced Breast Cancer: Pathological Response Predicts For Survival. Breast Cancer Res. & Treat. 124:723-732. PMID: 20878462
  • Ramírez-Valle, F., Badura, M.,  Braunstein S. and Schneider, R.J. (2010). Mitotic raptor promotes mTORC1 activity, G2/M cell cycle progression and IRES-dependent mRNA translation. Mol. Cell. Biol., 30:3151-3164. PMID: 20439490
  • Sadri, N., Lu, J.-Y., Badura, M. and Schneider, R.J. (2010). AUF1 is involved in splenic follicular B cell maintenance. BMC Immunology 11: 1-14. PMID: 20064252
  • Bauer, J.A., Bapsi Chakravarthy, A., Rosenbluth, J.M., Mi, D., Seeley, E.H., De Matos Granja, N., Olivares, M.G., Kelley, M.C., Mayer, I.A., Meszoely, I.M., Means-Powell, J.A., Johnson, K.N., Tsai, C.J., Ayers,G.D., Sanders, M.E., Schneider, R.J., Formenti, S.C., Caprioli, R.M., and Pietenpol, J.A. (2010). Identification of Markers of Taxane-Sensitivity Through Proteomic and Genomic Analyses of Breast Tumors from Patients Receiving Neoadjuvant Paclitaxel/Radiation Therapy. Clinical Cancer Research 16:680-690. PMID: 20068102
  • Silvera, D., Formenti, S.C. and Schneider, R.J. (2010).  Translational control in cancer.  Nature Reviews Cancer 10:254-266. PMID: 20332778
  • Silvera, D. and Schneider, R.J. (2009). Inflammatory breast cancer cells are constitutively adapted to hypoxia. Cell Cycle 19: 3089-3094. PMID: 19755858
  • Braunstein, S., Badura, M., Xi, Q., Formenti, S.C. and Schneider, R.J. (2009).  Regulation of protein synthesis by ionizing radiation. Mol. Cell. Biol. 29: 5645-5656. PMID: 19704005
  • Silvera D, Arju R, Darvishian F,  Levine P, Goldberg, J.G., Hockman, T., Formenti SC and Schneider RJ.  (2009). Essential Role for eIF4GI Overexpression in Inflammatory Breast Cancer Pathogenesis. Nature Cell Biology 11:903-910. PMID: 19525934
  • Sadri, N. and Schneider, R.J. (2009). Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. J. Invest. Derm. 129, 657–670. PMID: 18830269
  • Matsumura, S., Wang. B., Kawashima, N., Braunstein, S., Badura, M., Cameron, T.O., Babb, J.S., Schneider, R.J., Formenti, S.C., Dustin, M.L. and Demaira, S. (2008). Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J. Immunology 181: 3099-3107. PMID: 18713980
  • Ramírez-Valle, F. Braunstein S., Zavadil, J., Formenti, S.C., and Schneider, R.J. (2008). eIF4GI Links Nutrient Sensing by mTOR to Cell Proliferation and Inhibition of Autophagy. J. Cell Biol. 181: 293-307. PMID: 18426977
  • Braunstein, S., Formenti, S. C. and Schneider, R.J. (2008).  TNF selects for stable inducible upregulation of NF-kB linked to radiation resistance in weakly transformed breast cancer cells.  Mol. Cancer Res. 6:78-88. PMID: 18234964
  • Braunstein, S., Karpisheva, K., Pola, C., Goldberg, J., Hockman, T., Yee, H., Cangiarella, J., Arju. R., Formenti, S.C., and Schneider, R.J. (2007). A hypoxia controlled cap-dependent to cap-independent translation switch in breast cancer. Mol. Cell,28: 501-512. PMID: 17996713