Keywords: Inflammation, oxidative-stress, signal transduction, gene discovery, functional genomics and proteomics, gene regulation, molecular immunology, cancer research and neuro-inflammation.
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-LRR 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.
Transcriptosome profiling, mass spectroscopy and proteome analysis, gene-ablation in mice and RNA interference, various models for cancer, autoimmune and inflammatory diseases.
June Brickey, Ph.D.
Justin Callaway, Ph.D.
Liang Chen (Leo) – grad student
Ning Cheng, grad student
Weichun Chou (Emily), Ph.D.
Meng Deng – grad student
Les Freeman – grad student
Haitao Guo, Ph.D.
Elizabeth Guthrie, Ph.D.
Brandon Johnson, Ph.D.
Rob Junkins, Ph.D.
Alicia Koblansky, Ph.D.
Cate Kurkjian, Ph.D.
Xin Li, Ph.D.
Rong Liu, grad student
Yoshi Oyama, M.D.
Alex Petrucelli, Ph.D.
Karen Swanson, Ph.D.
Michael Thompson, MS
Aga Truax, Ph.D.
Toru Uchimura, M.D.
Justin Wilson, Ph.D.
Co-Director, Inflammatory Diseases Institute
Director, Center for Translational Immunology
Program Leader, Lineberger Comprehensive Cancer Center
UCRF Program Planning Committee