Xiaoxia Li, PhD
The Paul L. Fox, PhD, Endowed Chair in Molecular Medicine at the Lerner Research Institute
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
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.
- IL-17/IL-25 Signaling
- IL-1R-Toll-like receptor-mediated signaling
- Sigirr, a negative regulator of Toll-IL-1R signaling
- Inflammasome, inflammation and Disease
Below are representative Publications (For whole publications, please visit
Chen X, Cai G, Liu C, Zhao J, Gu C, Wu L, Hamilton TA, Zhang CJ, Ko J, Zhu L, Qin J, Vidimos A, Koyfman S, Gastman BR, Jensen KB, Li X.
J Exp Med. 2018 Dec 21.
Zhang CJ, Jiang M, Zhou H, Liu W, Wang C, Kang Z, Han B, Zhang Q, Chen X, Xiao J, Fisher A, Kaiser WJ, Murayama MA, Iwakura Y, Gao J, Carman J, Dongre A, Dubyak G, Abbott DW, Shi FD, Ransohoff RM, Li X.
J Clin Invest. 2018 Dec 3;128(12):5399-5412.
Zhang CJ, Wang C, Jiang M, Gu C, Xiao J, Chen X, Martin BN, Tang F, Yamamoto E, Xian Y, Wang H, Li F, Sartor RB, Smith H, Husni ME, Shi FD, Gao J, Carman J, Dongre A, McKarns SC, Coppieters K, Jørgensen TN, Leonard WJ, Li X.
Nature communications. 2018; 9(1):2745.
Cai G, Zhu L, Chen X, Sun K, Liu C, Sen GC, Stark GR, Qin J, Li X.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11531-11536.
Herjan T, Hong L, Bubenik J, Bulek K, Qian W, Liu C, Li X, Chen X, Yang H, Ouyang S, Zhou H, Zhao J, Vasu K, Cockman E, Aronica M, Asosingh K, Licatalosi DD, Qin J, Fox PL, Hamilton TA, Driscoll D, Li X.
Nature immunology. 2018; 19(4):354-365.
Liu W, Liu X, Li Y, Zhao J, Liu Z, Hu Z, Wang Y, Yao Y, Miller AW, Su B, Cookson MR, Li X, Kang Z.
The Journal of experimental medicine. 2017; 214(10):3051-3066.
Wang C, Zhang CJ, Martin BN, Bulek K, Kang Z, Zhao J, Bian G, Carman JA, Gao J, Dongre A, Xue H, Miller SD, Qian Y, Hambardzumyan D, Hamilton T, Ransohoff RM, Li X.
Nat Commun. 2017 May 31;8:15508.
Zhou H, Bulek K, Li X, Herjan T, Yu M, Qian W, Wang H, Zhou G, Chen X, Yang H, Hong L, Zhao J, Qin L, Fukuda K, Flotho A, Gao J, Dongre A, Carman JA, Kang Z, Su B, Kern TS, Smith JD, Hamilton TA, Melchior F, Fox PL, Li X.
Elife. 2017 Oct 9;6. pii: e29630.
Zhao J, Sun L, Li X.
Immunity. 2017 Feb 21;46(2):165-167.
Liu C, Zhu L, Fukuda K, Ouyang S, Chen X, Wang C, Zhang CJ, Martin B, Gu C, Qin L, Rachakonda S, Aronica M, Qin J, Li X.
Sci Signal. 2017 Feb 21;10(467).
Zhou H, Yu M, Zhao J, Martin BN, Roychowdhury S, McMullen MR, Wang E, Fox PL, Yamasaki S, Nagy LE, Li X.
Hepatology (Baltimore, Md.). 2016; 64(6):1978-1993
Martin BN, Wang C, Zhang CJ, Kang Z, Gulen MF, Zepp JA, Zhao J, Bian G, Do JS, Min B, Pavicic PG Jr, El-Sanadi C, Fox PL, Akitsu A, Iwakura Y, Sarkar A, Wewers MD, Kaiser WJ, Mocarski ES, Rothenberg ME, Hise AG, Dubyak GR, Ransohoff RM, Li X.
Nature immunology. 2016; 17(5):583-92.
Zhao J, Bulek K, Gulen MF, Zepp JA, Karagkounis G, Martin BN, Zhou H, Yu M, Liu X, Huang E, Fox PL, Kalady MF, Markowitz SD, Li X.
Gastroenterology. 2015; 149(7):1860-1871
Researchers led by Dr. Li identified a novel signaling cascade that links inflammation and colorectal cancer, where elevated levels of the pro-inflammatory protein interleukin 17 leads to an accumulation of intracellular copper and ultimately disrupts anti-tumoral defenses.