The Laird Laboratory’s goal is to develop a detailed understanding of the molecular basis of human disease, with a particular emphasis on the role of epigenetics in cancer. Cancer often is considered to have a primarily genetic basis, with contributions from germline variations in risk and somatically acquired mutations, rearrangements, and copy number alterations. However, it is clear that non-genetic mechanisms can exert a powerful influence on cellular phenotype, as evidenced by the marked diversity of cell types within the human body, virtually all of which contain an identical genetic code. This is accomplished by differential gene expression controlled by tissue-specific transcription factors and variations in chromatin packaging and modification, which provides stable phenotypic states governed by epigenetic—not genetic—mechanisms. It seems intrinsically likely that an opportunistic disease such as cancer would take advantage of such a potent mediator of cellular phenotype. The Laird Laboratory is dedicated to understanding how epigenetic mechanisms contribute to the origins of cancer and how to translate this knowledge into more effective cancer prevention, detection, treatment, and monitoring.
One of the best-understood epigenetic marks is the covalent modification of DNA as 5-methylcytosine in CpG dinucleotides. The Laird team uses a multidisciplinary approach to understand the role of DNA methylation in cancer, relying in part on technology developed by Dr. Laird and colleagues, mechanistic studies in model organisms and cell culture, clinical and translational collaborations, genome scale and bioinformatic analyses, and epidemiological studies. In recent years, the Laird team has participated in the generation and analysis of high-dimensional epigenetic data sets, including the production of all epigenomic data for The Cancer Genome Atlas (TCGA) and the application of next-generation sequencing technology to single-base-pair resolution, whole-genome DNA methylation analysis. The lab leverages this epigenomic data for translational applications and hypothesis testing in animal models. A major focus of the Laird Laboratory is to develop mouse models for investigating epigenetic mechanisms and drivers of cancer, and to develop novel strategies for single-cell epigenomic analysis.