Xiaogang Li, Ph.D.

Professor of Medicine
Professor, Department of Biochemistry and Molecular Biology (secondary) and Director, Epigenetic Core Center
University of Kansas Cancer Center Cancer Biology – Faculty
Institute for Reproductive Health & Regenerative Medicine – Faculty
Department of Internal Medicine, Division of Nephrology and Hypertension

Ph.D., University of Minnesota, Twin City, MN
Postdoctorial, Harvard Medical School, Boston, MA


Research Focus

The primary focus of my research is to understand the molecular pathogenesis of autosomal dominant polycystic kidney diseases (ADPKD) and to translate these findings for ADPKD treatment. To this end, my lab has two emphasis areas of research:

1. TNF-alpha signaling and inflammation in ADPKD. We found that a tumor necrosis factor-α-mediated pathway promoting cyst growth and treatment with a TNF-α inhibitor etanercept prevented cyst formation in Pkd2+/- mice (Li et al., Nature Medicine, 2008). This is the first study to link renal inflammation to cystogenesis in ADPKD. We also found that a second mitochondria-derived activator of caspase (Smac)-mimetic, induces TNFα-dependent cystic renal epithelial cell death specifically, leading to the removal of cystic epithelial cells from renal tissues, thus, preventing cyst growth, which helped to clarify the role of apoptosis in the regulation of cyst size and in a larger sense might open a new approach to target renal cysts and prevent their endless expansion by the administration of Smac-mimetics (Fan et al., JASN, 2013). We further found that macrophage migration inhibitory factor (MIF) promotes cyst growth via modulation of cell proliferation and apoptosis, glucose metabolism, and macrophage recruitment in ADPKD (Chen et al., JCI, 2015). We are now focusing on the crosstalk of TNF-alpha signaling/renal inflammatory signaling and other PKD associated signaling pathways.

2. Epigenetics and ADPKD. We have conducted extensive research on the roles of histone deacetylases (HDACs) and histone methyltransferases (HMTs) in ADPKD. We found that: 1) Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts (Xia et al., Development, 2010); 2) Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation (Fan et al., Kidney International, 2012); 3) HDAC6 regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation in renal epithelial cells (Liu et al., Plos One. 2013); 4) Sirtuin 1 inhibition delays cyst formation in autosomal dominant polycystic kidney disease (Zhou et al., JCI 2013); 5) SIRT2 regulates ciliogenesis and contributes to loss of polycystin-1 mediated abnormal centrosome amplification; (Zhou et al., HMG, 2014); 6) Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD (Zhou et al., HMG, 2015), and 7) Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease (Linda Li et al., JCI, 2017). Currently we are focusing on, 1) Aberrant histone and/or protein methylation, and/or DNA methylation of CpG island containing promoters leads to permanent silencing of genes in both physiological and pathological contexts in cystic epithelial cells; 2) the roles of histone methylation regulates deletion of heart polycystin-1 mediated cardiac hypertrophy; and 3) Crosstalk of HSP90 signaling and epigenetic regulators in cystic renal epithelial cells.

My secondary research focus is to understand the molecular pathogenesis of breast cancer and translate these findings for cancer treatment. To this end, my lab is focusing on the roles of epigenetic regulators in regulation of breast cancer development, including the roles of DNA and histone methylation in breast cancer.

Selected Publications


Linda X. Li, Fan LX, Zhou JX, Grantham JJ, Calvet JP, Sage J, and Xiaogang Li. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. Journal Clinical Investigation, In Press. 2017.  

Chen L, Zhou X, Fan LX, Yao Y, Swenson-Fields KI, Gadjeva M, Wallace DP, Peters DJM, Yu A, Grantham JJ, Xiaogang Li. Macrophage migration inhibitory factor promotes cyst growth in polycystic kidney disease. Journal Clinical Investigation, 125(6):2399-2412, 2015.  

Zhou X, Fan LX, Peters DJM, Trudel M, Bradner JE, Xiaogang Li. Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD. Human Molecular Genetics. 24(14): 3982-3993, 2015.  

Zhou X, Fan LX, Li K, Ramchandran R, Calvet JP, Xiaogang Li. SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1. Human Molecular Genetics. 23(6):1644-55, 2014. PMCID: PMC3929098  

Zhou X, Fan LX, Sweeney, WE, Denu JM, Avner ED, Xiaogang Li. Sirtuin 1 inhibition delays cyst formation in autosomal dominant polycystic kidney disease. Journal Clinical Investigation. 123(7):3084-3098, 2013. PMCID: PMC4101988  

Fan LX, Zhou X, Sweeney, WE, Wallace DP, Avner ED, Grantham JJ, Xiaogang Li. Smac-mimetic dependent epithelial cell death reduces the growth of renal cysts. JASN. (12):2010-22, 2013. PMCID: PMC3839552  

Fan LX, Li X, Magenheimer BS, Calvet JP, Xiaogang Li. Inhibition of histone deacetylases targets the transcription regulator Id2 to attenuate cystic epithelial cell proliferation. Kidney Int. 81:76-85, 2012. PMID: 21900881. PMCID: PMC3409467.  

Xiaogang Li. Epigenetics and autosomal dominant polycystic kidney disease. Biochim Biophys Acta. 1812:1213-1218, 2011. PMCID: PMC3413450.  

Xiaogang Li, Magenheimer BS, Xia S, Johnson T, Wallace DP, Calvet JP, Li R. A tumor necrosis factor-alpha-mediated epigenetic switch promoting autosomal dominant polycystic kidney disease. Nature Med. 14:863-8, 2008. PMID: 18552856. PMCID: PMC3359869.  

Xiaogang Li, Luo Y, McNamara CA, Pei Y., and Zhou J. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nature Cell Biol. 7(12): 1202-12, 2005. PMID: 16311606.  

Book and Book Chapters:

1.      Xiaogang Li. Editor. 2015. Book entitled "Polycystic Kidney Disease". Edited by Xiaogang Li. Codon Publications. Australia. Note: This is the first PKD book in NIH NCBI bookshelf with 20 chapters.                  

https://www.ncbi.nlm.nih.gov/books/NBK373386/  

2.      Xiaogang Li. 2015. Chapter title: "Epigenetics in ADPKD:  Understanding Mechanisms and Discovering Treatment." Codon Publications. Australia.  

3.      Julie X. Zhou and Xiaogang Li. 2015. Chapter title: "The Role of Apoptosis in Polycystic Kidney Disease." Codon Publications. Australia.

Last modified: Jun 07, 2017

Contact

Xiaogang Li, Ph.D.
Professor of Medicine
Professor, Department of Biochemistry and Molecular Biology (secondary) and Director, Epigenetic Core Center
University of Kansas Cancer Center Cancer Biology – Faculty
Institute for Reproductive Health & Regenerative Medicine – Faculty

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