As principal investigator in Mayo Clinic's Polycystic Kidney Disease (PKD) Epigenetics and Inflammation Laboratory, Xiaogang Li, Ph.D., is studying molecular mechanisms associated with cyst formation. He is particularly focused on epigenetics, inflammation and the cross-talk of epigenetics and inflammation in PKD and other human diseases, including breast cancer and ciliopathies.
Epigenetics and PKD. Recent evidence indicates that epigenetic mechanisms other than changes in the underlying DNA sequence contribute to cystogenesis. Epigenetic mechanisms include DNA methylation and histone modifications that together alter the accessibility of transcriptional factors to DNA, leading to the alteration of specific signaling pathways that regulate cyst initiation and progression.
Dr. Li seeks to determine how patients' inherited PKD gene mutations favor the development of epigenetic changes, and how these changes can be characterized by different epigenetic techniques, including DNA methylation assay, ChIP and ChIP-sequencing assays, and single-cell sequencing analysis. Such characterizations will increase understanding of PKD pathophysiology and help researchers identify novel therapeutic targets for PKD treatment.
- Tumor necrosis factor (TNF)-alpha and inflammatory signaling in PKD. Recent evidence indicates that renal inflammation, such as TNF-alpha signaling as well as macrophages and T cells, contributes to cystogenesis. Dr. Li seeks to determine how inherited PKD gene mutations favor the development of inflammatory changes in cystic kidneys, and to identify novel therapeutic targets for PKD treatment.
- Understanding the mechanisms of cilium biogenesis. Primary cilia are microtubule-based sensory organelles projecting from the surface of eukaryotic cells. These cilia play fundamental roles as photosensors, mechanosensors and biochemical sensors. Primary cilia dysfunction results in developmental and degenerative disorders that combine to give rise to a large spectrum of human diseases affecting almost every major organ. Dr. Li seeks to determine if and how epigenetic regulators and inflammatory factors are involved in regulating cilium biogenesis and function.
Barriers to studying PKD epigenetics. Epigenetic changes are a major hallmark of kidney diseases and suggest mechanisms for altered gene expression in such diseases. However, due to this, several barriers exist that may impede investigators from conducting epigenetic research in PKD, including precise application of epigenetic techniques, data collection and analysis with verified standards.
Dr. Li and the PKD Epigenetics and Inflammation Laboratory provide consulting and a broad array of services targeted at generating molecular data from biospecimens with epigenetic techniques, including DNA methylation assay, ChIP and ChIP-sequencing assays, and single-cell sequencing analysis, particularly using biospecimens from patients with kidney diseases and animal models.
Significance to patient care
Dr. Li's research in epigenetics and inflammation will improve diagnostics and prognostics of PKD and related diseases.
- Recipient, Team Science Award, Mayo Clinic, 2020