- ASSOCIATE PROFESSOR Medicine, Clinical Immunology
BA, Luther College
PhD, Mayo Clinic
Dept. of Genetics, Harvard Medical School
Dept. of Molecular Biology, Massachusetts General Hospital
Specific Clinical/Research Interest:
Antiviral immune response; signal transduction in cell survival and cell death; molecular mechanisms of inflammation
Current Student: Scott Justus (MIC)
Instructors: Marie Anne O'Donnell, Diana Legarda-Addison
The lab has several areas of interest: (1) dissecting the ubiquitin-modifying machinery that determines survival versus death following cellular activation by the TNF family of cytokines; (2) understanding the post-translational regulation of early host response to viral infection.
Summary of Research Studies:
Stimulation of TNF receptor 1 (TNFR1) leads to either cell survival or to cell death and Caspase 8 is well known to initiate the death program known as apoptosis. We recently showed that Caspase 8 can also have the opposite function of promoting cell survival by cleaving and causing the degradation of CYLD, a tumor suppressor that removes lysine 63-linked polyubiquitin chains. By removing CYLD, Caspase 8 inhibits the induction of a novel cell death process known as programmed necrosis or necroptosis. We are now conducting further studies to understand the role of CYLD in programmed necrosis and how this novel cell death pathway may be involved in tumorigenesis and microbial infections.
O’Donnell MA, Perez-Jimenez E, Oberst A, Ng A., Massoumi R, Xavier R, Green DR, Ting AT. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol 2011; 13:1437-1442.
O’Donnell MA, Ting AT. RIP1 comes back to life as a cell death regulator in TNFR1 signaling. FEBS J 2011; 278:877-887.
O’Donnell MA, Ting AT. Chronicle of a death foretold: dual sequential cell death checkpoints in TNF signaling. Cell Cycle 2010; 9:1065-1071.
Legarda-Addison D, Hase H, O’Donnell MA, Ting AT. NEMO/IKKg regulates an early NF-kB-independent cell death checkpoint during TNF signaling. Cell Death & Diff 2009; 16:1279-1288.
Friedman CS, O'Donnell MA, Legarda-Addison D, Ng A, Cardenas WB, Yount JS, Moran TM, Basler CF, Komuro A, Horvath CM, Xavier R, Ting AT. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated anti-viral response. EMBO Reports 2008; 9: 930-936.
Legarda-Addison D, Ting AT. Negative regulation of TCR signaling by NF-kappaB2/p100. J. Immunol 2007; 178: 7767-7778.
O'Donnell MA, Legarda-Addison D, Skountzos P, Yeh WC, Ting AT. Ubiquitination of RIP1 regulates an NF-kappaB-independent cell death switch in TNF signaling. Curr. Biol 2007; 17: 418-424.
Yang M, Hase H, Legarda-Addison D, Varughese L, Seed B, Ting AT. BCMA, the receptor for APRIL and BAFF, induces antigen presentation in B cells. J. Immunol 2005; 175: 2814-2824.
He KL, Ting AT. Essential role for IKKgamma/NEMO in TCR-induced IL-2 gene expression in Jurkat T cells. Eur. J. Immunol 2003; 33: 1917-1924.
He KL, Ting AT. A20 inhibits tumor necrosis factor (TNF) alpha-induced apoptosis by disrupting recruitment of TRADD and RIP to the TNF receptor 1 complex in Jurkat T cells. Mol. Cell. Biol 2002; 22: 6034-6045.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Ting did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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