|Assistant Professor of MCD Biology
B. A., Trinity College Dublin
Ph.D., Trinity College Dublin
Postdoctorate, UMASS Medical School and UC San Francisco
Protection against infection and maintenance of homeostasis are the hallmarks of the innate immune system. An inducible program of inflammatory gene expression is central to anti-microbial defenses and while acute inflammation is mostly beneficial, uncontrolled inflammation can have devastating consequences leading to a wide range of diseases such as Arthritis, Systemic Lupus Erythematous and Cancer. Given the significance of these devastating diseases, new approaches to understanding pathology and gene mechanism are needed.
One of the most fascinating findings following the sequencing of the human genome is that less than 3% of the genome codes for protein coding exons. It is now appreciated that over 85% of the genome is actively transcribed and the biggest challenge we are faced with is to understand the functional role for these transcripts. Long noncoding RNA (lncRNA) represent the largest class of RNA transcripts produced from the genome. lncRNA are defined as transcripts greater than 200 nucleotides in length lacking protein-coding exons. In recent years lncRNAs have emerged as major regulators of chromatin remodeling, transcription and post-transcriptional regulation of gene expression in diverse biological contexts. Our goal is to understand the functions for lncRNA within Innate Immunity.
There are approximately 16,000 lncRNAs identified in the human genome but this number continues to increase as more sequencing data is obtained. These genes show strong cell type and tissue specific expression patterns. Our main focus is to study lncRNAs expressed in Macrophages and Dendritic cells and try to learn how they impact inflammatory signaling. First we use deep sequencing technology to identify differentially regulated lncRNA following inflammatory activation. We study lncRNA localization using fluorescence in situ hybridization and carry out loss and gain of function experiments to understand how these lncRNA regulate gene expression in our pathways of interest. LncRNA are emerging as an additional layer in the regulation of immune responses where they can promote, fine-tune and restrain the inflammatory program. Understanding the molecular mechanisms that govern the transcriptional regulation of genes in inflammatory and infectious conditions will provide insight and perhaps one-day novel therapeutic targets.
Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.