Greally Lab research

Mechanisms of human disease

We have been studying molecular genomic (epigenetic) mechanisms of mammalian phenotypes for many years, developing genome-wide assays and analytical approaches to facilitate this work.

Our current work moves upstream from DNA methylation and histone states to transcription factors, cell signalling, and the interaction with DNA sequence variation in the non-coding genome.

Current projects include a molecular and cellular dissection of processes occurring in ageing T lymphocytes, the formation of fibrosis-producing myofibroblasts in liver, new insights into the effects of endocrine-disrupting chemicals in adipogenesis, and the dysregulatory properties of de novo variants in neurodevelopmental disorders.

Stem cell research

We are developing in vitro models of human diseases using differentiation of mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs). We are partnering with the New York Stem Cell Foundation and New York Blood Center to develop a diverse iPSC bank to promote equity in the research that uses these cellular resources.

Somatic mosaicism

The modest changes in DNA methylation associated with phenotypes has prompted us to consider the possibility that mosaic subpopulations of cells can mediate human phenotypes. We are increasingly involved in studies to test for mosaicism in human phenotypes, with our MAD-seq approach designed to reveal chromosomal events. We are also working on the stem cell origins of clonal haematopoiesis in collaboration with Uli Steidl.

Clinical genomics

The patient population of the Bronx highlights the challenges and opportunities involved with providing clinical genetic services to very diverse people. Our recent involvement in the CSER2 program was focused on the development of tools to enhance the clinician input into genomic diagnostics, the GenomeDiver approach, now in a pilot clinical trial.

Data visualisation

We have an interest in data visualisation, summarised in this presentation, that led us to develop the open-source Pcaso tool. Our eventual goal is to develop an Open Genomics Visualization Initiative that brings together people with an interest in this topic to work in a virtual collaborative environment.