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
Brief Description 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
Xiaojuan Li, PhD, director of the Program of Advanced Musculoskeletal Imaging (PAMI), has received a 5-year, $3 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to develop a quicker method to assess changes in the knee that lead to osteoarthritis (OA).
Copper is a heavy metal that plays an essential role in cellular metabolism and other biological functions. In the presence of inflammation, copper levels increase in tissues and are thought to be beneficial, enhancing the body’s defense against infection. On the other hand, copper is also known to be elevated in cancer cells and has specifically been shown to promote colorectal cancer progression.
A multicenter team of researchers led by Xiaojuan Li, PhD, Department of Biomedical Engineering, Lerner Research Institute, and Kurt Spindler, MD, Orthopaedic & Rheumatology Institute, has received a 5-year, $3.1 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (part of the National Institutes of Health) to help identify long-term risk factors for osteoarthritis after an anterior cruciate ligament (ACL) tear and reconstruction.
A group of Lerner Research Institute scientists, led by Xiaoxia Li, PhD, Department of Inflammation & Immunity, defined a new link between inflammation, wound healing and tumor formation. The pathway they discovered provides valuable insights into the study of inflammation-associated cancers.
Xiaojuan Li, PhD, Staff in the Department of Biomedical Engineering and Founding Director of the Program of Musculoskeletal Imaging, has been appointed the inaugural Bonutti Family Endowed Chair for Musculoskeletal Research. This endowment illustrates both Lerner Research Institute’s robust musculoskeletal imaging program and the translational and bidirectional nature of research at Cleveland Clinic.