Yee Ling Wu, Ph.D.

Yee Ling Wu, Ph.D.

Assistant Professor

Ph.D.  Ohio State University

Major Research Interests:  Immune regulation of antibody generation and genetic diversity of innate immunity in health and diseases

 

 

The generation of antibodies (immunoglobulins, Ig) with great diversity is key in immune protection against microbes. However, antibodies can also mediate diseases including type-I hypersensitivity (e.g. asthma and allergy) and autoimmune diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis and Sjögren’s Syndrome). My research team is interested in studying the molecular mechanisms by which different antibodies arise and what renders antibodies protective in one context but detrimental in another, using both animal models and human samples.

Allergy and Asthma.  Immunoglobulin isotype E (IgE) is a major player in protective responses against worm infections, but is also a main mediator for asthma and allergy. Antibodies are highly diverse in their specificity and affinity to antigens as well as in their effector functions. In the case of IgE, the molecular pathway (class switch recombination) by which they are generated also differs and may have direct impact on the functions of the IgE molecules produced.

Our current focus is to determine the molecular signals and cellular interactions that regulate the generation of IgE using both in vitro and in vivo systems. We investigate the different pathways by which IgE molecules arise, evaluate the functional differences of these IgE molecules as well as their contributions to pathological responses. We anticipate that this research will yield important knowledge for IgE biology and for developing novel therapeutic strategies against asthma and allergy.

Systemic autoimmune diseases.  Anomalies in the generation of autoantibodies against self-antigens result in massive production of immune complexes, which trigger the activation of the complement system, cumulating in tissue injuries and chronic diseases. The cause for the generation of autoantibodies is still unclear. A recent discovery is the unexpected gene copy number variations (CNVs) of many innate immune response genes (e.g. human complement C4A and C4B, and the immunoglobulin receptors FCGR3B and FCGR3A) among human subjects. CNVs of immune response genes not only lead to quantitative and qualitative diversities of the innate immunity against infections, but also lead to differential predispositions to autoimmune diseases. Our team is interested in deciphering the link between innate diversity (attributed to gene CNVs) and adaptive immunity as well as the pathogenic mechanisms of systemic autoimmune diseases.

 

Wu YL, Stubbington MJ, Daly M, Teichmann SA and Rada C.  Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE. J. Exp Med. 2017: Jan; 214 (1): 183-196. PMID: 27994069.

Chen JY*, Wu YL*, Mok MY, Wu YJ, Lintner KE, Wang CM, Chung EK, Yang Y, Zhou B, Wang H, Yu D, Alhomosh A, Jones K,Spencer CH, Nagaraja HN, Lau YL, Lau CS and Yu CY.   Effects of Complement C4 Gene copy-Number variations, size dichotomy and C4A-deficiency on genetic risk and clinical presentation of SLE in East-Asians (*authors contributed equally).Arthritis Rheumatol 2016: Jan 27. PMID: 26814708.

Taylor BJ, Wu YL and Rada C. Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes. eLife 2014:  doi:10.7554/eLife.03553. PMID: 25237741.

Taylor BJ, Nik-Zainal S, Wu YL, Stebbings LA, Raine K, Campbell PJ, Rada C, Stratton MR, Neuberger MS.  Kataegic mutation showers through the action of the APOBEC family of DNA deaminases. eLife 2013: 41(2):485-90. Doi:10.7554/eLife.00534. PMID: 23599896.

Wu YL, Brookshire BP, Verani RR, Arnett FC, Yu CY. Clinical presentations and molecular basis of complement C1r deficiency in a male African-American patient with systemic lupus erythematosus. Lupus 2011: 20(11):1126-34. PMID: 21784777.

Shen N, Fu Q, Deng Y, Qian X, Zhao J, Kaufman KM, Wu YL, Yu CY, Tang Y, Chen JY, Yang W, Wong M, Kawasaki A, Tsuchiya N, Sumida T, Kawaguchi Y, Howe HS, Mok MY, Bang SY, Liu FL, Chang DM, Takasaki Y, Hashimoto H, Harley JB, Guthridge JM,  Grossman JM, Cantor RM, Song YW, Bae SC, Chen S, Hahn BH, Lau YL, Tsao BP. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc Natl Acad Sci USA 2010: 107(36):15838-43. PMID: 20733074.

Wu YL, Hauptmann G, Viguier M, Yu CY. Molecular basis of complete complement C4 deficiency in two North-African families with systemic lupus erythematosus. Genes Immun 2009: 10(5):433-45. PMID: 19279649.

Wu YL, Savelli SL, Yang Y, Zhou B, Rovin B, Birmingham DJ, Nagaraja HN, Hebert LA and Yu CY. Sensitive and specific real-time PCR assays to accurately determine copy number variations (CNVs) of human complement C4A, C4B, C4-long, C4-short and RCCX modules: Elucidation of C4 CNVs in 50 consanguineous subjects with defined HLA genotypes. J Immunol 2007: 179: 3012-3025. PMID: 17709516.

Yang Y, Chung EK, Wu YL, Savelli S, Nagaraja HN, Zhou B, Hebert M, Jones K, Shu Y, Kitzmiller K, Blanchong CA, McBride K, Higgins GC, Rennebohm RM, Rice RR, Hackshaw KV, Roubey RA, Grossman JM, Tsao BP, Birmingham DJ, Rovin BH, Hebert LA and Yu CY. Gene copy number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): Low copy number is a risk factor for and high copy number is a protective factor against European American SLE disease susceptibility. Am J Hum Genet 2007:80:1037-1054. PMID: 17503323

Wu YL, Higgins GC, Rennebohm RM, Chung EK, Yang Y, Zhou B, Nagaraja HN, Birmingham  DJ, Rovin BH, Hebert LA and Yu CY. Three distinct profiles of serum complement C4 proteins in pediatric systemic lupus erythematosus (SLE) patients: Tight associations of complement C4 and C3 protein levels in SLE but not in healthy subjects.  Adv Exp Med Biol 2006:586:227-247. PMID: 16893076.

 

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