Department of Immunology
Xiaoxia Li, Ph.D.
The Paul L. Fox, PhD, Endowed Chair in Molecular Medicine at the Lerner Research Institute
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 445-8706
Fax: (216) 444-9329
The general focus of my laboratory is to investigate the signaling mechanisms in innate and adaptive immunity. Our approaches include gene discovery, mapping of signaling networks in cell culture models and in vivo functional analyses done through gene knock-out and knock-in techniques in mice.
We aim to develop a system that links gene discovery to signaling pathways and eventually to set up animal models of disease by manipulating genes of interest through mouse genetics. The long-term objective is to develop therapeutic drugs to treat different immune diseases through collaboration with scientists in biotechnology companies.
A major focus of my laboratory is to investigate IL-1 receptor/Toll-like receptor (IL-1R-TLR) signaling mechanisms. Our goal is to study the molecular mechanisms by which the IL-1R-TLRs mediate signaling, with the long-term aim of developing more effective anti-inflammatory small-molecule drugs. We discovered a negative regulator for IL-1R-TLR signaling, the single immunoglobulin IL-1 receptor related molecule (SIGIRR). We continue to investigate the detailed molecular mechanisms by which SIGIRR negatively regulates the IL-1R/TLR pathway and how SIGIRR modulates intestinal mucosal immunity.
We have also discovered an adapter molecule called Act1 that has an important role in regulating autoimmunity through its impact on both T- and B-cell-mediated immune responses.
Recent studies have shown that Act1 is also a key positive signaling component for the IL-17 signaling pathway, critical for TH17-mediated autoimmune and inflammatory responses.
In other words ...
- IL-17/IL-25 Signaling
- IL-1R-Toll-like receptor-mediated signaling
- Sigirr, a negative regulator of Toll-IL-1R signaling
- CD40- and BAFF-mediated B cell survival
- Intestinal inflammation
Gulen M. F., Kang Z. , Bulek K., Youzhong W., Kim T. W. , Chen Y., Altuntas C. Z., Bak-Jenson K. , McGeachy M. J., Do J. S. , Xiao H., Delgoffe G. M. , Min B., Powell J. D., Tuohy V. K., Cua D. J., Li X. (in press) The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation. Immunity.
Kang Z., Altuntas C, Gulen MF, Liu C , Giltiay N, Qin H, Ransohoff R, Bergmann C, Stohlman S, Tuohy V, Li X. (2010) Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis. Immunity
Swaidani S., K.Bulek, Z.Kang, C.Liu, Y.Lu, W.Yin, M.Aronica, and Li X (2009) The Critical Role of Epithelial-Derived Act1 in IL-17- and IL-25-Mediated Pulmonary Inflammation. J.Immunol. 182:1631-1640.
Hartupee J, Li X and Hamilton T (2009) IL-17 signaling for mRNA stabilization does not required TRAF6. J. Immunol. 182:1660-6
Bulek K, Swaidani S, Qin J, Lu Y, Gulen M, Herjan T, Min B, Kastelein R, Aronica M, Li X (2009) The essential role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulation of Th2 immune response. J. Immunol.
Wan Y, Thomas J, Li X (2009) Interleukin-1 Receptor-associated Kinase 2 Is Critical for
Lipopolysaccharide-mediated Post-transcriptional Control. J. Biol. Chem.
Staschke K, Dong S, Saha J, Zhao J, Brooks N, Hepburn D, Xia J, Gulen M, Kang Z, Altuntas C, Tuohy V, Gilmour R, Li X and Na S (2009) IRAK4 kinase Activity is Required for Th17 Differentiation and TH17 -Mediated Disease. J. Immunol.
Liu C, Qian W, Qian, Giltiay G, Misra S, Chen Z, and Li X (2009) Act1, a U-box E3 ubiquitin ligase for IL-17R signaling. Science Signaling
Xiao H, Gilmour R, and Li X . (2008) Pellino 3b negatively regulates IL-1-induced TAK1-dependent NF k B activation. J. Biol. Chem.
Hartupee J, Li X and Hamilton T (2008) Interleukin 1-induced NFB Activation and Chemokine mRNA Stabilization Diverge at IRAK1. J. Biol. Chem. 283:15689-93.
Von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, Chrabieh M, Mustapha IB, Ghandil P, Camcioglu Y, Vasconcelos J, Sirvent N, Guedes M, Vitor AB, Herrero-Mata MJ, Aróstegui JI, Rodrigo C, Alsina L, Ruiz-Ortiz E, Juan M, Fortuny C, Yagüe J, Antón J, Pascal M, Chang HH, Janniere L, Rose Y, Garty BZ, Chapel H, Issekutz A, Maródi L, Rodriguez-Gallego C, Banchereau J, Abel L , Li X, Chaussabel D, Puel A, Casanova JL. (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321: 691-6.
Fraczek J, Kim T, Xiao H, Yao J, Wen Q, Yali Li, Jean-Laurent Casanova, and Li X (2008) The kinase activity of IRAK4 is required for IL-1R/TLR-induced TAK1-dependent NFkappa B activation. J. Biol. Chem.
Qian Q, Giltiay G, Scott M, Robert Carter; Trine N. Jorgensen; and Li X (2008) Deficiency of Act1, a critical modulator of B cell function, leads to development of Sjogren's syndrome. Euro. J. Immunol.