Robert J Schneider, PhD

Robert J ScneiderAlbert Sabin Professor of Molecular Pathogenesis;
Associate Director for Translational Research, NYU Cancer Institute
Ph.D., 1985 Mount Sinai School of Medicine

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: (preferred method of contact)

Research Theme(s): Breast cancer, Inflammation, Control of Protein Synthesis and mRNA Translation, Cancer Stem Cells
Keywords: Cancer Stem Cells, Breast Cancer, mTOR, Translational Regulation, Metastasis, Mesenchymal Transition

Research Summary:

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 (2006-2011):