Xiaogang Li, Ph.D.

Associate Professor of Medicine
Kidney Institute - Faculty
University of Kansas Cancer Center Cancer Biology – Full Member
Institute for Reproductive Health & Regenerative Medicine – Full Member
Department of Internal Medicine, Division of Nephrology and Hypertension

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


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 and treatment of Pkd2+/- mice with the TNF-α inhibitor etanercept prevented cyst formation. This study uncovered the connection among TNF-α signaling, polycystins and cystogenesis. (Li et al., Nature Medicine, 2008). 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 formation, 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). Recently, we found that macrophage migration inhibitory factor 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 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 function 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); and 6) Therapeutic targeting of BET bromodomain protein, Brd4, delays cyst growth in ADPKD (Zhou et al., HMG, 2015, In press). 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.

The secondary focus of my research is to understand the molecular pathogenesis of breast cancer and to 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

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. J Clin Investigation, In Press. 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. In Press. 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. J Clin 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

Liu W, Fan LX, Zhou X, Sweeney WE Jr., Avner ED, Xiaogang Li. HDAC6 regulates epidermal growth factor receptor (EGFR) endocytic trafficking and degradation in renal epithelial cells. PLoS One. 7:e49418, 2012. (In Press) PMID: 23152903. PMCID: 3496684.

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.

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

Xia S, Li X, Johnson T, Seidel C, Wallace DP, and Li R. Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts. Development. 137:1075-84, 2010. PMID: 20181743. PMCID: PMC2835323.

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. Nat Med. 14:863-8, 2008. PMID: 18552856. PMCID: PMC3359869.

Li, Xiaogang, 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.

Last modified: Apr 14, 2015

Contact

Xiaogang Li, Ph.D.
Associate Professor of Medicine
Kidney Institute - Faculty
University of Kansas Cancer Center Cancer Biology – Full Member
Institute for Reproductive Health & Regenerative Medicine – Full Member

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