The complement system is an important part of the innate immunity. Complement activation products not only directly help to eliminate invading pathogens, but also participate in many immunological reactions, including clearance of immune complexes, antibody production, and T-cell regulation. Insufficient or excess complement activation has been shown to be important in a wide range of disease states, such as multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis, and age-related macular degeneration, as well as in allograft rejection.
Using genetically engineered mice as disease models, my laboratory is interested in studying complement activation and regulation in these disease states, thus eventually developing novel therapies. In our latest work, for example, we have found evidence of a potentially clinically useful connection of complement in mesenchymal stem cell-based therapies, suggesting that complement is a valid target for improving the viability and function of mesenchymal stem cells, which are under extensive evaluation in clinical trials for treating many inflammatory and degenerative diseases.
For the past several years, we have been collaborating with Cleveland Clinic researchers, and as of January 2013, our laboratory relocated to the Lerner Research Institute. We welcome and look forward to forming many new collaborations, as well as identifying clinical applications for our work with complement in autoimmune diseases and transplant rejection.
Zhidan Tu, Yan Li, Dawn Smith, Nader Sheibani, Suber Huang, Timothy Kern and Feng Lin (2011): Retinal pericytes inhibit activated T cell proliferation Invest Ophthalmol Vis Sci. 52(12):9005-10
Zhidan Tu, Yan Li, Dawn Smith, Catherine Doller, Sunao Sugita, Chi-Chao Chan, Shiguang Qian, John Fung, Rachel R Caspi, Lina Luand Feng Lin (2012) Myeloid suppressor cells induced by retinal pigment epithelial cells inhibit autoreactive T cell responses that lead to experimental autoimmune uveitis Invest Ophthalmol Vis Sci. 53(2):959-66.
Yan Li and Feng Lin (2012) Mesenchymal stem cells are attacked by complement after infusion Blood, 120(17):3436-43
Michael Strainic, Ethan Shevach, Fengqi An, Feng Lin, and Edward Medof (2012) Absent C3aR/C5aR signaling into CD4+ T cells enable auto-inductive TGF-β1 signaling and induction of foxp3+ T regulatory cells Nature Immunology, 14(2):162-71
Posterior uveitis is inflammation of the back part of the uvea, a layer of tissue beneath the white of the eye. A common cause of blindness, the disease can be the result of autoimmune disorders, which occur when the immune system sends out T cells to attack and destroy healthy tissue.