Current Projects
Identifying tissue specific enhancers that regulate adaptation to exercise.
Lack of exercise is recognized as the fourth highest risk factor for death and contributes to over 40 chronic diseases. Exercise adaptation is a complex whole-body process that requires multiple tissues, cell types and signaling pathways. What has remained a mystery is how exercise signals are communicated to chromatin and how this results in a change in gene expression. We aim to understand how noncoding regions called “enhancers” regulate the gene expression response to exercise and how this communication is dysregulated in metabolic disease.
Determining how our environment affects the spatial and temporal relationship of how enhancers come into 3D proximity with their target genes.
Enhancers bind transcription factors in a cell- and tissue-specific manner to help regulate gene expression. This is achieved in both a spatial and temporally controlled manner, such that enhancers often need to come into close proximity with their target genes in order to maximize a transcriptional response; this is referred to as chromatin looping. We aim to understand how chromatin looping is established and maintained and how these processes govern our ability to respond to environmental stimuli.
How We Do It:
We employ a multi-disciplinary approach that utilizes physiological, biological and genomic techniques. Learn more about our various methods below.
Gene expression analysis
Gene expression is fundamental to tissue development and adaptation. We utilize various methods to understand the transcriptomic changes that take place during and across adaptation. These include bulk techniques such as RNA-seq as well as single cell methods.
Chromatin dynamics and 3D conformation
Chromatin state and three-dimensional architecture are dynamic and responsive to environmental inputs. We use cutting edge tools to help understand how chromatin integrates environmental inputs into transcriptional outputs. These include CUT&Tag, CUT&RUN and Chromosome Confirmation Capture sequencing technologies such as Hi-C and pcHi-C.
Epigenome editing
CRISPR tools, including CRISPR Cas9 and CRISPR dCas9, provide us with the ability to directly interrogate a cell’s epigenome, its necessity and its role in tissue plasticity.
Tissue culture
Tissue culture allows us to isolate our variables of interest that is not always feasible in animal models. We both create and work with novel cell lines and primary tissues to investigate the role of chromatin looping and enhancer activation in tissue adaptation.
Muscle phenotyping
Tissues change considerably after exercise interventions and their changes must be tracked accordingly. We utilize various tools to help us better understand how tissues change over time giving us insight into general rules and heterogeneity of adaptation.
Genetic mouse models
Mouse models are an invaluable tool that help us determine how one change affects a whole organism. By genetically modifying mice, we are able to investigate phenotypic changes that occur from specific genetic alterations.