A word cloud of the abstracts from Dr. Leung’s previous publications. This image illustrates the essence of the Leung lab’s research.
Mammalian genomes consist mostly of non-coding sequences. Within this massive proportion, previously misclassified as “junk DNA”, resides elements that function to regulate normal transcriptional programs. We are particularly interested in two classes of non-coding sequences: cis-regulatory elements (transcriptional promoters and enhancers) and endogenous retroviruses.
Our research focuses on dissecting how non-coding sequences are epigenetically regulated in both normal development and disease. We utilize various epigenomic and cell biology tools to delineate epigenetic pathways that modulate the activities of cis-regulatory elements and endogenous retroviruses and their downstream effects on gene expression.
Project 1: Developmental Epigenomics
We are interested in understanding how the non-coding genome is epigenetically regulated in developmental processes, including pluripotent stem cell differentiation and placental development.
- Retrotransposons in maintaining totipotency and pluripotency
- Non-coding DNA elements in placental cell differentiation
Project 2: Higher-order chromatin structure
We use integrative approaches to study the epigenetic mechanisms that control how mammalian genomes are organized in the 3D space of the nucleus. In particular, we are interested in how histone modifications regulate chromatin looping.
- Role of histone modifications and DNA methylation in maintaining genome architecture
- Epigenetic regulation of cis-regulatory interactions
Project 3: Cancer Epigenomics
We define epigenome features, such as retrotransposon dysregulation, specific to cancer cells and delineate their roles in oncogenesis. We currently have ongoing projects on hepatocellular carcinoma, melanoma, and glioblastoma.
- Role of non-coding DNA to Glioblastoma
- Retrotransposons in hepatocellular cellular carcinoma
- Epigenomic dysregulation in melanoma
Project 4: Neuroepigenomics
We aim to elucidate non-coding epigenomic changes in neurological disorders and connect them to transcriptomic and functional phenotypes. Specifically, we are focused on the contribution of retrotransposons in Alzheimer’s Disease, multiple sclerosis, and mild traumatic brain injuries.
- Contribution of retrotransposons in neurodegenerative diseases
- Epigenomic alterations from mild traumatic brain injury
Project 5: Epigenomic response to autoimmunity and viral infection
We analyze the epigenetic consequences of autoimmunity and viral infections. The de-repression of retrotransposons can trigger epigenomic and transcriptomic alterations associated with the innate immune response.
- Epigenomic reprogramming associated with SARS-CoV-2 infection
- Contribution of retrotransposons in autoimmune diseases
Dr. Leung was a researcher in the NIH Roadmap Epigenomics project, for which the video below was produced. This clip provides a general view of what epigenetics and epigenomics research is about.