Biography

Dr. Hugo Sepulveda is a Bioengineer in molecular biology, Master in Biochemistry and Bioinformatics and PhD in Molecular Biosciences. He completed his PhD under supervision of Dr. Martin Montecino at Universidad Nacional Andres Bello (UNAB), graduating in 2016. In 2018, he joined the laboratory of Dr. Anjana Rao at Jolla Institute for Immunology (LJI) and Sanford Consortium for Regenerative Medicine (SCRM), at University of California San Diego (USCD) as a postdoctoral research fellow, sponsored by The Pew Latin American Fellows Program and The California Institute for Regenerative Medicine (CIRM). There, Hugo focused on studying how Epigenetic mechanisms, especially modifications on DNA (5mC and 5hmC) and chromatin proteins (methylation and O-GlcNAc) control the expression of genes and Transposable Elements (TEs) in development and diseases. Particularly, he focused in understating the functional connections between the chromatin proteins, TETs (5hmC writers) and OGT (O-GlcNAc writer) that shapes the Epigenome, determining also their impacts in maintaining the (Epi)Genome stability and cellular identity. He also collaborates with several international teams applying cutting-edge molecular tools and Bioinformatic methods to explore and discover the regulatory principles controlling these regions.

Research Description

The laboratory of Dr. Hugo Sepulveda investigates how Epigenetic mechanisms determine chromatin states to control Transcription and cellular identity. They focus on understanding how chromatin proteins, such as TETs (5hmC writers), DNMTs (5mC writers), and OGT (O-GlcNAc writer), shape the Epigenome. Their research aims to investigate the patterns and roles of DNA modifications in mammalian cells, as well as how other chromatin complexes interact with the DNA methylation machinery to integrate them into the Epigenetic code. While genes uncover ~2% of the genome and are mainly found in euchromatin, the other 98% consists of highly repetitive sequences primarily located in heterochromatin, the transcriptionally silent chromatin domain in normal cells. Sepulveda’s lab studies the mechanisms and consequences of heterochromatin disruption, a phenomenon frequently found in diseases including autoimmune and neurological disorders and cancers, which is characterized by increased expression of thousands of transposable elements (TEs), descendants of ancient viruses accumulated in our genome over evolution. The lab aims to investigate how some of these TEs, including some members of LINEs and ERVs families, can also acts as regulatory elements (e.g., alternative promoters), determining their functional roles in diseases, chromatin architecture and gene expression. They are also studying the epigenetic repressive complexes controlling these elements and the specific events that reactivate them in diseases. To achieve this, they utilize cutting-edge bioinformatics, genetic, molecular, cellular and biochemical methods to explore these uncharted territories of chromatin research.