Xiaoxia Li, Ph.D.
Staff
The Paul L. Fox, PhD, Endowed Chair in Molecular Medicine at the Lerner Research Institute
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Location: NE4-307
Email: lix@ccf.org
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.
In other words ...
- IL-17/IL-25 Signaling
- IL-1R-Toll-like receptor-mediated signaling
- Sigirr, a negative regulator of Toll-IL-1R signaling
- Autoimmunity
- Inflammasome, inflammation and Disease
- Immunometabolism
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Katarzyna Bulek, PhD Visiting Scientist |
Location:NE4-256 Phone:(216) 445-8707 bulekk@ccf.org |
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Xing Chen, PhD Research Associate |
Location:NE4-256 Phone:(216) 445-8707 chenx@ccf.org |
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Bing Han Predoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 hanb@ccf.org |
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Tomasz Herjan, PhD Research Associate |
Location:NE4-256 Phone:(216) 445-8707 herjant@ccf.org |
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Lingzi Hong Graduate Student |
Location:NE4-256 Phone:(216) 445-8707 hongl@ccf.org |
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Michal Jandzinkski Visiting Researcher |
Location:NE4-256 Phone:(216) 445-8707 jandzim@ccf.org |
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Zizhen Kang, PhD Staff Scientist |
Location:NE4-256 Phone:(216) 445-8707 kangz@ccf.org |
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Yun Liao, PhD Postdoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 liaoy@ccf.org |
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Weiwei Liu, PhD Postdoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 liuw@ccf.org |
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Caini Liu, PhD Project Staff |
Location:NE4-256 Phone:(216) 445-8707 liuc@ccf.org |
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Jin Z. Ma Research Technician |
Location:NE4-256 Phone:(216) 445-8707 maj@ccf.org |
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Aaron Miller, PhD Project Staff |
Location:NE4-300I Phone:(216) 444-1721 millera25@ccf.org |
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William Miller-Little Graduate Student |
Location:NE4-256 Phone:(216) 445-8707 millerw@ccf.org |
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Suidong Ouyang, PhD Research Associate |
Location:NE4-256 Phone:(216) 445-8707 ouyangs@ccf.org |
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Wen Qian, PhD Research Associate |
Location:NE4-256 Phone:(216) 445-8707 qianw@ccf.org |
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Fangqiang Tang, PhD Postdoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 tangf@ccf.org |
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Han Wang, BS Predoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 wangh3@ccf.org |
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Jianxin Xiao, PhD Senior Research Technologist |
Location:NE4-256 Phone:(216) 445-8707 xiaoj@ccf.org |
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Quanri Zhang, PhD Postdoctoral Research Fellow |
Location:NE4-256 Phone:(216) 445-8707 zhangq2@ccf.org |
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Junjie Zhao Research Associate |
Location:NE4-256 Phone:(216) 445-8707 zhaoj2@ccf.org |
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Hao Zhou, MD, PhD Research Associate |
Location:NE4-256 Phone:(216) 445-8707 zhouh@ccf.org |
Below are representative Publications (For whole publications, please visit
IL-17R-EGFR axis links wound healing to tumorigenesis in Lrig1+ stem cells.
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.
TLR-stimulated IRAKM activates caspase-8 inflammasome in microglia and promotes neuroinflammation.
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.
Act1 is a negative regulator in T and B cells via direct inhibition of STAT3.
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.
TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation.
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.
LRRK2 promotes the activation of NLRC4 inflammasome during Salmonella Typhimurium infection.
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.
IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.
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.
Commanding CNS Invasion: GM-CSF.
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
T cell-intrinsic ASC critically promotes T(H)17-mediated experimental autoimmune encephalomyelitis.
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
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