Jenny PY Ting, PhD

Jenny P. Y. Ting, Ph.D.Professor

Co-Director, Inflammatory Diseases Institute
Director, Center for Translational Immunology
Program Leader, Lineberger Comprehensive Cancer Center
UCRF Program Planning Committee
22-004 Lineberger Comprehensive Cancer Center, CB #
7295

919.966.5538

jenny_ting@med.unc.edu


Research

Dr. Ting’s laboratory has broad interest in the application of cutting edge ideas and technology to the study of disease-relevant issues. Major directions include innate immunity, dendritic cell function, cell death, autophagy, signal transduction, gene discovery, functional genomics and proteomics, nanoparticles, gene regulation, neuro-inflammation and microglial cells. Clinical issues of interest include multiple sclerosis, cancer, autoimmune diseases, biologic therapy, infection and inflammation.

Immune gene transcription

Dr. Ting has studied the transcriptional master regulator of class II Major Histocompatibility (MHC) genes called CIITA (class II transactivator) for over a decade. CIITA is extremely important as patients with defects in the gene exhibit severe immunodeficiency.. CIITA promotes the recruitment of DNA-binding protein, transcription cofactors, and histone acetylases/methylases to the class II MHC promoters. More recently, her lab has found that another protein, NLRC5, which has a similar domain structure as CIITA can broadly regulate class I MHC in mice by modifying chromatin structure. Thus NLRC5 and CIITA are master regulators of class I and II MHC, which play central roles in adaptive immune activation.

NLRs: The NBD-LLR proteins regulate inflammatory cytokines, signaling and cell death

Based on the structure of CIITA, Dr. Ting found a large family of genes that encode similar structural motifs as CIITA. This was initially termed the CATERPILLER gene family, and now have been renamed NLRs. NLRs are important for immune defense against bacteria, viruses, fungi, parasites and damage-associated molecules. Mutations in NLRs are the primary genetic causes of several immunologic disorders. Beyond inflammation and infection, her group showed a strong effect of NLRs on cancer and metabolic diseases. RNA interference, gene ablation, genomics, yeast two-hybrid, biochemical and proteomics analyses are performed to understand the functions of these novel genes.

The Detrimental and Beneficial Roles of CNS Inflammation in Disease Progression and Resolution

Inflammation occurs in a number of neurologic diseases such as Alzheimer's, Parkinson's, Huntington's and multiple sclerosis (MS). Using mice with mutations in inflammatory genes, Dr. Ting found that many of these genes, such as NLRs and cytokines, are not only crucial in disease progression (demyelination), but also in disease resolution (remyelination).

The role of immune plexins and semaphorins

Dr. Ting’s work in the plexin and semaphorin family originated because her lab found that CIITA also regulate plexin-A1 gene expression. Plexin-A1 is typically thought to be important for neuronal interaction and retraction. Her new finding presents a new framework to think about how immune cells attract and repulse each other. Her lab found that plexin-A1 and it ligand, Semaphorin 6D, are important for T cell activation. Additionally, they showed that Plexin-A4 and Semaphorin 3A interaction is important in sepsis, Plexin-D1 plays an important role in B cell activation, and Plexin-B2 influences cell movement. Thus this family has broad immune functions.

Core Techniques

Transcriptosome profiling, mass spectroscopy and proteome analysis, gene-ablation in mice and RNA interference, various models for cancer, autoimmune and inflammatory diseases.

Publications

Barker BR, Taxman DJ, Ting JP (2011). Cross-regulation between the IL-1β/IL-18 processing inflammasome and other inflammatory cytokines. Curr Opin Immunol.

Allen IC, Moore CB, Schneider M, Lei Y, Davis BK, Scull MA, Gris D, Roney KE, Zimmermann AG, Bowzard JB, Ranjan P, Monroe KM, Pickles RJ, Sambhara S, Ting JP (2011). NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I-MAVS and TRAF6-NF-κB signaling pathways. Immunity. 34(6):854-65.

Taxman DJ, Holley-Guthrie EA, Huang MT, Moore CB, Bergstralh DT, Allen IC, Lei Y, Gris D, Ting JP. (2011). The NLR adaptor ASC/PYCARD regulates DUSP10, mitogen-activated protein kinase (MAPK), and chemokine induction independent of the inflammasome. J Biol Chem. 286(22):19605-16.

Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP (2011). Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 12(5):408-15.

Holl EK, O'Connor BP, Holl TM, Roney KE, Zimmermann AG, Jha S, Kelsoe G, Ting JP (2011). Plexin-D1 is a novel regulator of germinal centers and humoral immune responses. J Immunol. 186(10):5603-11.

Davis BK, Wen H, Ting JP (2011). The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 29:707-35. Review.

Davis BK, Roberts RA, Huang MT, Willingham SB, Conti BJ, Brickey WJ, Barker BR, Kwan M, Taxman DJ, Accavitti-Loper MA, Duncan JA, Ting JP (2011). Cutting edge: NLRC5-dependent activation of the inflammasome. J Immunol. 186(3):1333-7

McNally RS, Davis BK, Clements CM, Accavitti-Loper MA, Mak TW, Ting JP (2011). DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB. J Biol Chem. 286(6):4098-106.

van Deventer HW, Burgents JE, Wu QP, Woodford RM, Brickey WJ, Allen IC, McElvania-Tekippe E, Serody JS, Ting JP (2010). The inflammasome component NLRP3 impairs antitumor vaccine by enhancing the accumulation of tumor-associated myeloid-derived suppressor cells. Cancer Res. 70(24):10161-9.

Jha S, Srivastava SY, Brickey WJ, Iocca H, Toews A, Morrison JP, Chen VS, Gris D, Matsushima GK, Ting JP (2010). The inflammasome sensor, NLRP3, regulates CNS inflammation and demyelination via caspase-1 and interleukin-18. J Neurosci. 30(47):15811-20.

Wen H, Lei Y, Eun SY, Ting JP (2010). Plexin-A4-semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm. J Exp Med. 207(13):2943-57.

Huang MT, Mortensen BL, Taxman DJ, Craven RR, Taft-Benz S, Kijek TM, Fuller JR, Davis BK, Allen IC, Brickey WJ, Gris D, Wen H, Kawula TH, Ting JP (2010). Deletion of ripA alleviates suppression of the inflammasome and MAPK by Francisella tularensis.
J Immunol. 185(9):5476-85.

Arthur JC, Lich JD, Ye Z, Allen IC, Gris D, Wilson JE, Schneider M, Roney KE, O'Connor BP, Moore CB, Morrison A, Sutterwala FS, Bertin J, Koller BH, Liu Z, Ting JP (2010). Cutting edge: NLRP12 controls dendritic and myeloid cell migration to affect contact hypersensitivity. J Immunol. 185(8):4515-9.

McElvania Tekippe E, Allen IC, Hulseberg PD, Sullivan JT, McCann JR, Sandor M, Braunstein M, Ting JP (2010). Granuloma formation and host defense in chronic Mycobacterium tuberculosis infection requires PYCARD/ASC but not NLRP3 or caspase-1. PLoS One. 5(8):e12320.

Taxman DJ, Huang MT, Ting JP (2010). Inflammasome inhibition as a pathogenic stealth mechanism. Cell Host Microbe. 8(1):7-11. Review.

Gris D, Ye Z, Iocca HA, Wen H, Craven RR, Gris P, Huang M, Schneider M, Miller SD, Ting JP (2010). NLRP3 plays a critical role in the development of experimental autoimmune encephalomyelitis by mediating Th1 and Th17 responses. J Immunol. 185(2):974-81.

Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP (2010). The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med. 207(5):1045-56.

Davis BK, Ting JP (2010). NLRP3 has a sweet tooth.
Nat Immunol. 11(2):105-6. Review.

Jha S, Ting JP (2009). Inflammasome-associated nucleotide-binding domain, leucine-rich repeat proteins and inflammatory diseases. J Immunol. 183(12):7623-9. Review.

Willingham SB, Allen IC, Bergstralh DT, Brickey WJ, Huang MT, Taxman DJ, Duncan JA, Ting JP. (2009). NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and -independent pathways. J Immunol. 183(3):2008-15.

Duncan JA, Gao X, Huang MT, O'Connor BP, Thomas CE, Willingham SB, Bergstralh DT, Jarvis GA, Sparling PF, Ting JP (2099). Neisseria gonorrhoeae activates the proteinase cathepsin B to mediate the signaling activities of the NLRP3 and ASC-containing inflammasome. J Immunol. 182(10):6460-9.

Lei Y, Moore CB, Liesman RM, O'Connor BP, Bergstralh DT, Chen ZJ, Pickles RJ, Ting JP (2009). MAVS-mediated apoptosis and its inhibition by viral proteins. PLoS One. 4(5):e5466.

Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP (2009). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity. 30(4):556-65.

Huang MT, Taxman DJ, Holley-Guthrie EA, Moore CB, Willingham SB, Madden V, Parsons RK, Featherstone GL, Arnold RR, O'Connor BP, Ting JP (2009). Critical role of apoptotic speck protein containing a caspase recruitment domain (ASC) and NLRP3 in causing necrosis and ASC speck formation induced by Porphyromonas gingivalis in human cells. J Immunol. 182(4):2395-404.

O'Connor BP, Ting JP (2008). The evolving role of semaphorins and plexins in the immune system: Plexin-A1 regulation of dendritic cell function. Immunol Res. 41(3):217-22.

Willingham SB, Ting JP (2008). NLRs and the dangers of pollution and aging. Nat Immunol. 9(8):831-3.

Moore CB, Ting JP (2008). Regulation of mitochondrial antiviral signaling pathways. Immunity. 28(6):735-9.

Ting JP, Willingham SB, Bergstralh DT (2008). NLRs at the intersection of cell death and immunity. Nat Rev Immunol. 8(5):372-9.

Ting JP, Lovering RC, Alnemri ES, Bertin J, Boss JM, Davis BK, Flavell RA, Girardin SE, Godzik A, Harton JA, Hoffman HM, Hugot JP, Inohara N, Mackenzie A, Maltais LJ, Nunez G, Ogura Y, Otten LA, Philpott D, Reed JC, Reith W, Schreiber S, Steimle V, Ward PA (2008). The NLR gene family: a standard nomenclature. Immunity. 28(3):285-7.

Ye Z, Ting JP (2008). NLR, the nucleotide-binding domain leucine-rich repeat containing gene family.
Curr Opin Immunol. 20(1):3-9.

Iocca HA, Plant SR, Wang Y, Runkel L, O'Connor BP, Lundsmith ET, Hahm K, van Deventer HW, Burkly LC, Ting JP (2008). TNF superfamily member TWEAK exacerbates inflammation and demyelination in the cuprizone-induced model. J Neuroimmunol. 194(1-2):97-106.

Moore CB, Bergstralh DT, Duncan JA, Lei Y, Morrison TE, Zimmermann AG, Accavitti-Loper MA, Madden VJ, Sun L, Ye Z, Lich JD, Heise MT, Chen Z, Ting JP (2008). NLRX1 is a regulator of mitochondrial antiviral immunity. Nature. 451(7178):573-7.

Ye Z, Lich JD, Moore CB, Duncan JA, Williams KL, Ting JP (2008). ATP binding by monarch-1/NLRP12 is critical for its inhibitory function. Mol Cell Biol. 28(5):1841-50.

Lich JD, Williams KL, Moore CB, Arthur JC, Davis BK, Taxman DJ, Ting JP. Cutting Edge: Monarch-1 Suppresses Non-Canonical NF-kappaB Activation and p52-Dependent Chemokine Expression in Monocytes. J Immunol., Cutting Edge. 178(3):1256-60, 2007.

Bergstralh DT, Conti BJ, Moore CB, Brickey WJ , Taxman DJ , and Ting JP. Global functional analysis of nucleophosmin in Taxol response, cancer, chromatin regulation, and ribosomal DNA transcription. Exp Cell Res. 313:65-76, 2007.

Duncan JA, Bergstralh DT, Wang Y, Willingham SB, Ye Z, Zimmermann AG, Ting JP. Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc. Natl. Acad. Science 104: 8041-6, 2007.

Duncan JA and Ting JP. Rebuilding Host-Pathogen Interaction from the Ground Up: In Vitro Reconstitution of the Inflammasome Cell, Host and Microbes. 1:7-9, 2007.

Plant SR, Wang Y., Vasseur S., Thrash JC, McMahon E, Arnett, HA, Miller S, Carson, MJ, Iovanna JL, and Ting JP. Upregulation of the stress-associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues. Glia. 53(5):529-37, 2006.

Ting JP, Hoffman HA, Kastner D. CATERPILLER genes and periodic fever syndromes. Nature Rev. Immunol. March 6(3):183-95, 2006.

Hoffman BG, Williams KL, Tien AH, Lu V, de Algara TR, Ting JP, Helgason CD. Identification of novel genes and transcription factors involved in spleen, thymus and immunological development and function. Genes and Immunity. 7(2):101-12, 2006.

Taxman DJ, Livingstone LR, Zhang J, Conti BJ, Iocca HA, Williams KL, Lich JD, Ting JP, Reed W. Criteria for effective design, construction, and gene knockdown by shRNA vectors. BMC Biotechnol. 24(6):7, 2006.

Lich JD, Arthur JA, Ting JP. Cryopyrin: in from the cold. Immunity. 24(3):241-3, 2006.

Bergstralh DT, Ting JP. Microtubule stabilizing agents: Their molecular signaling consequences and the potential for enhancement by drug combination. Cancer Treat Rev. 32(3):166-79. 2006.

Eun Y, O’Connor BP, Wong AW, van Deventer H, Taxman DJ, Reed W, Li P, Blum JS, McKinnon KP, Ting JP. Rho activation and actin polarization are dependent on plexin-A1 in dendritic cells. J. Immunol. Cutting Edge, Oct 177(7):4271-5, 2006.

Clements CM, McNally RS, Conti BJ, Mak TW, Ting JP. DJ-1/PARK 7 stabilizes the anti-oxidant transcriptional master regulator, Nrf2: Implications in cancer and Parkinson’s disease. Proc. Natl. Acad. Science, 103(41):15091-6, 2006.

Taxman DJ, Zhang J, Champagne C, Bergstralh DT, Iocca HA, Lich JD, Ting JP. ASC mediates the induction of multiple cytokines by Porphyromonas gingivalis via caspase 1-dependent and independent pathways. J. Immunol. Cutting Edge, 177(7):4252-6, 2006.

Plant SR, Arnett HA, Ting JP. Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination. Glia. 49(1):1-14, 2005.

Ting JP and Davis B. CATERPILLER: A novel gene family important in immunity, cell death and diseases. Annu Rev Immuno. 23:387-414, 2005.

Zika E and Ting JP. Epigenetic control of MHC-II: Interplay between CIITA and histone modifying Enzymes. Current Opinion in Immunology, 17(1):58-64, 2005.

Conti BJ, Davis BK, Zhang J, O'Connor W, Williams KL, and Ting JP. Caterpiller 16.2 (CLR16.2): A novel NBD/LRR family member that negatively regulates T cell function. J. Biol. Chem. 280:18375-18385; 2005.

Williams KL, Lich JD, Rallabhandi P, Reed W, Kurtz S, Coffield VM, Su L, Vogel SN, Braunstein M and Ting JP. Monarch-1 is an Antagonist of TLR-induced Pro-inflammatory Signal Transduction. J. Biol. Chem. 280:39914-24, 2005.

Zika E, Fauquier L, Vandel L, Ting JP. Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN-{gamma}-inducible MHC-II gene expression. Proc Natl Acad Sci. 102(45):16321-6, 2005.

Complete list of publications

Accomplishments

Outstanding Research into the Cause and Cure of Multiple Sclerosis

National Multiple Sclerosis Society, 2001

Teaching Excellence Award

University of North Carolina at Chapel Hill, 2002

Award for Outstanding Contribution to the field of Immunology and Immunity to Infections

American Society for Microbiology, 2003

Sandler Program in Asthma Research Award, 2005

Service

NIH ALY study section member, 1992-1996; miscellaneous NIH study sections, ad hoc 2002-2006 annually; chair, 2003, 2004, 2005; NCI intramural site visit reviewer 2000, 2005

Journal of Immunology, Associate Editor, 1991-1993, Section Editor, 1994-1998

Molecular Cell. Biology, Editorial Board, 1997 - present

National Multiple Sclerosis Society, Study Section Member, 1997 to 2002

Wellcome Trust Elion-Hitchings Fellowship Advisory Committee, 1998-2002

American Association of Immunologists, Publication Committee, 1999-2003

Reviewer: Nature, Science, Cell, Nature Immunol., Nature Neuro., Nature Rev. Immunol., Immunity, Mol. Cell., J. Exp. Med., Proc. Natl. Acad. Sci., Mol. Cell. Biol.,J. Immunol., J. Biol. Chem., Trends in Immunol.

Affiliations

Co-Director, Inflammatory Diseases Institute

Director, Center for Translational Immunology

Program Leader, Lineberger Comprehensive Cancer Center

UCRF Program Planning Committee

Department of Microbiology-Immunology

Lineberger Comprehensive Cancer Center

The Curriculum in Neurobiology

Curriculum in Genetics and Molecular Biology (CGMB)

Biological and Biomedical Sciences Program (BBSP)