A/Prof. Lu Jinhua
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine
My research focus is antinuclear autoimmunity and systemic lupus erythematosus (SLE).
SLE is a complex autoimmune disease that affects multiple organs and has heterogeneous manifestations. Many of the patients’ symptoms can be explained by autoantibodies specific for protein and nucleic acid antigens. However, it remains unclear how these antinuclear autoantibodies (ANA) are generated. Numerous genetic variations, or deficiencies, contribute to ANA induction and SLE disease development. It is particularly striking that deficiency in a group of four intimately related complement proteins– C1q, C1r, C1s, C4–can cause ANA production and severe SLE disease. We recently discovered that C1q binds to the nucleolus in late apoptotic cells. The nucleolus is a prominent target of ANA and we found that C1q binding to the nucleolus causes activation of the C1r/C1s proteases, which then degrade autoantigens in the nucleolus. However, it remains unclear how this causes C4 opsonization of nucleoli and regulation of B cell responses to nucleolar antigens. Our studies on the structure of the nuclei and nucleoli are revealing the molecular basis of the intrinsic autoimmunogenecity of the nuclear antigens.
Our special interest is in elucidating how B cells are rendered aberrant to produce these autoantibodies.
Our future research is aimed at understanding the mechanisms that lead to production of antinuclear autoantibodies.
My laboratory’s expertise is in studying complement, nuclear and nucleolar structures, immunity and lupus.
1. Neo JYJ, Wee SYK, Bonne I, Tay SH, Raida M, Jovanovic V, Fairhurst A-M, Lu J, Hanson BJ, MacAry PA (2019) Characterisation of a human antibody that potentially links cytomegalovirus infection with systemic lupus erythematosus
Scientific Reports 9:9998.
2. Chen J, Teo BHD, Lu J (2018) A Method for Extracting the Nuclear Scaffold from the Chromatin Network. Bio-protocol 8(8):e2821
3. Borghini L, Lu J, Hibberd M, Davila S (2018) Variation in Genome-Wide NF-κB RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile. Journal of Immunology 201(4):1295-1305.