Xiaogang Li, Ph.D.

Location

Contact

SUMMARY

Xiaogang Li, Ph.D., conducts research at Mayo Clinic on polycystic kidney disease (PKD), autosomal dominant polycystic kidney disease (ADPKD) and related conditions. Dr. Li studies molecular mechanisms associated with cyst formation, focusing on epigenetics, inflammation, and the crosstalk of epigenetics and inflammation in PKD, breast cancer, ciliopathies and aging.

Focus areas

• 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 inherited PKD gene mutations favor the development of epigenetic changes characterized by different epigenetic techniques, including DNA methylation assay, ChIP and ChIP-sequencing assay, and single-cell sequencing analysis. This work should increase understanding of PKD pathophysiology and identify novel therapeutic targets for PKD treatment.

• TNF-alpha and inflammatory signaling in PKD. Recent evidence indicates that renal inflammation, such as TNF-alpha signaling, 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, which 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 conditions that can affect almost any major body organ. Dr. Li seeks to determine if and how epigenetic regulators and inflammatory factors are involved in regulating cilium biogenesis and function.
• Gene therapy in ADPKD. Dr. Li seeks to apply AAV-mediated CRISPR-Cas9 base editing in various PKD gene animal models to correct harmful pathogenic changes.
• Senescence in ADPKD. Dr. Li seeks to determine whether senescent cells can directly drive ADPKD-related pathology and be therapeutically targeted in ADPKD.
• Epigenetics and senescence in aging. The process of aging results in a host of changes in epigenetic patterns over the lifespan, suggesting that epigenetic changes may be an important component in aging. Dr. Li seeks to understand the mechanisms of crosstalk between key epigenetic regulators and the senescence and aging process.

• Barriers to studying PKD epigenetics. Epigenetic changes are a major hallmark of kidney disease and suggest mechanisms for altered gene expression in kidney disease. However, research may be impeded by precise application of epigenetic techniques, data collection and analysis with verified standards. Dr. Li and his colleagues provide consulting and a broad array of services targeted at generating molecular data from biospecimens with epigenetic techniques. These services include DNA methylation assay, ChIP and ChIP-sequencing assay, and single-cell sequencing analysis, particularly in biospecimens from kidney disease in animal models and people.

Significance to patient care

Dr. Li's research in epigenetics and inflammation will improve the diagnosis and predicted outcomes of polycystic kidney disease and related conditions.