Xiaoxia  Li,  Ph.D.

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


Katarzyna  Bulek  PhD Katarzyna Bulek, PhD
Visiting Scientist
Location:NE4-256
Phone:(216) 445-8707
bulekk@ccf.org
Xing  Chen  PhD Xing Chen, PhD
Research Associate
Location:NE4-256
Phone:(216) 445-8707
chenx@ccf.org
Bing  Han  Bing Han
Predoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
hanb@ccf.org
Tomasz  Herjan  PhD Tomasz Herjan, PhD
Research Associate
Location:NE4-256
Phone:(216) 445-8707
herjant@ccf.org
Lingzi  Hong  Lingzi Hong
Graduate Student
Location:NE4-256
Phone:(216) 445-8707
hongl@ccf.org
Michal  Jandzinkski  Michal Jandzinkski
Visiting Researcher
Location:NE4-256
Phone:(216) 445-8707
jandzim@ccf.org
Zizhen  Kang  PhD Zizhen Kang, PhD
Staff Scientist
Location:NE4-256
Phone:(216) 445-8707
kangz@ccf.org
Yun  Liao  PhD Yun Liao, PhD
Postdoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
liaoy@ccf.org
Weiwei  Liu  PhD Weiwei Liu, PhD
Postdoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
liuw@ccf.org
Caini  Liu  PhD Caini Liu, PhD
Project Staff
Location:NE4-256
Phone:(216) 445-8707
liuc@ccf.org
Jin Z. Ma  Jin Z. Ma
Research Technician
Location:NE4-256
Phone:(216) 445-8707
maj@ccf.org
Aaron  Miller  PhD Aaron Miller, PhD
Project Staff
Location:NE4-300I
Phone:(216) 444-1721
millera25@ccf.org
William  Miller-Little  William Miller-Little
Graduate Student
Location:NE4-256
Phone:(216) 445-8707
millerw@ccf.org
Suidong  Ouyang  PhD Suidong Ouyang, PhD
Research Associate
Location:NE4-256
Phone:(216) 445-8707
ouyangs@ccf.org
Wen  Qian  PhD Wen Qian, PhD
Research Associate
Location:NE4-256
Phone:(216) 445-8707
qianw@ccf.org
Fangqiang  Tang  PhD Fangqiang Tang, PhD
Postdoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
tangf@ccf.org
Han  Wang  BS Han Wang, BS
Predoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
wangh3@ccf.org
Jianxin  Xiao  PhD Jianxin Xiao, PhD
Senior Research Technologist
Location:NE4-256
Phone:(216) 445-8707
xiaoj@ccf.org
Quanri  Zhang  PhD Quanri Zhang, PhD
Postdoctoral Research Fellow
Location:NE4-256
Phone:(216) 445-8707
zhangq2@ccf.org
Junjie  Zhao  Junjie Zhao
Research Associate
Location:NE4-256
Phone:(216) 445-8707
zhaoj2@ccf.org
Hao  Zhou  MD, PhD 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 

http://www.ncbi.nlm.nih.gov/sites/myncbi/xiaoxia.li.1/bibliograpahy/40545339/public/?sort=date&direction=ascending):

 

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.

 

IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling.

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.

 

IL-17 induced NOTCH1 activation in oligodendrocyte progenitor cells enhances proliferation and inflammatory gene expression.

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.

 

The flavonoid cyanidin blocks binding of the cytokine interleukin-17A to the IL-17RA subunit to alleviate inflammation in vivo.

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).

 

IRAKM-Mincle axis links cell death to inflammation: Pathophysiological implications for chronic alcoholic liver disease.

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.

 

Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

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


01/29/2019 |  

Defining the Link Between Inflammation and Cancer

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. 




02/15/2017 |  

New Grant to Study Autoimmune Condition that Causes Blindness

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.