YU LAB at VCU SOM - Research objectives

Our lab integrates multiple cutting edge approaches to study epigenetics, including protein and chromatin reconstitution, biochemical assay development, structure-function analysis, genomics and next-generation sequencing, bioinformatics, stem cell differentiation and organoid models, and pharmacological studies. We focus on key questions and collaborate with the best scientists to establish complementary approaches toward our research goals.

Basic Mechanisms of Chromatin Regulation

Cancer Epigenetics and Therapeutics

Epigenetic Dysregulation in Developmental Disorders

The balance between active and repressive chromatin is crucial to maintain proper gene expression in the context of normal development. Disruption of this process can lead to human developmental disorders and a wide spectrum of human cancers. We strive to investigate how chromatin regulators establish the balance and once it is established, how the epigenetic states are inherited from parental to daugher cells, a biological process termed epigenetic inheritance to safeguard cellular identities. During S phase in cell cycle, all the epigenetically modified histones must be removed to allow DNA replication, how do cells restore the epigenetic landscapre afterwards is a key topic of inquiries in the field.

Human cancers often carry driver mutations in epigenetic regulators. A case in point is crippled Polycomb Repressive Complex 2 (PRC2) leading to a global loss of repressive chromatin and an aberrant gain of active chromatin. This molecular group include many pediatirc and adult cancers, such as Malignant Peripheral Nerve Sheath Tumor (MPNST) (PRC2 deletion), Diffuse Midline Glioma (DMG) (H3K27M mutation), and Posterior Fossa Type A (PFA) Ependymoma (EZHIP derepression). We strive to understand the underlying biology and cancer vulnerabilities for therapeutic interventions.

Congenital mutations in epigenetic regulators that dirsupt the balance between active and repressive chromatin can lead to human overgrowth in multiple organs, such as Sotos Syndrome (NSD1 mutation) and MRXS34 Syndrome (NONO mutation). A hallmark is macrocephaly in the brain that causes intellecutal disabilities. Another focus in lab is a bone-specific overgrowth syndrome caused by human SPIN4 mutations. We seek to understand how these epigenetic dysregulation cause multi-organ versus organtropic human overgrowth syndromes at the chromatin, transcriptional, and cellular levels.

We appreciate the funding supports from: