Fundamental aspects of transcription regulation
Transcription is the first step in the conserved process of gene expression and plays essential roles in the growth, development and adaptation of all organisms. Despite its importance, the molecular mechanisms that control transcription are incompletely understood. Our goal is to understand the mechanisms driving transcriptional regulation. Current projects focus on understanding the role of Cdk8, a kinase and the only catalytic subunit of the Mediator transcription co-activator complex. Cdk8 has well-established roles in transcription regulation via the phosphorylation of core components of the transcriptional machinery and a set of transcription factors, activities that position Cdk8 at the nexus of general and context-specific transcription activation and repression.
Chromatin biology and cancer mutations on histone genes
In eukaryotic cells DNA exists in the context of chromatin, a structure that regulates genome function including transcription, DNA replication, and DNA repair. Histones are the protein component of nucleosomes, the basic unit of chromatin. Sequencing efforts have identified thousands of unique mutations mappings to histone genes. A subset, known as oncohistones, have been shown to drive oncogenesis. The best-known examples include histone H3-K27M, K36M, and G34W/R/V/L mutations, alterations that are remarkably frequent in certain types of cancer and predictive of patient health outcomes. For example, the H3-K27M mutation occurs in ~70% of pediatric diffuse intrinsic pontine gliomas, results in a 4.59 to 0.73 year reduction in patient survival, and is now recognized by the World Health Organization as a biomarker of a highly aggressive tumor - diffuse midline glioma H3K27M mutant. Current projects aim to understand normal histone function and how mutations on histone genes contribute to oncogenesis.
Genetic and epigenetic effects of wildfire smoke exposure
Wildfire smoke exposure is a global health concern that contributes to a variety of disease states including lung cancer. In Canada, wildfires are already the largest contributors to air pollution, and their severity and frequency is expected to increase as result of climate change. Currently, very little is known about the acute and long-term impacts of wildfire smoke exposure in human health and how this environmental insult disrupt transcription and chromatin biology. Our laboratory, aims to bridge this knowledge gap using the fruit fly model system. Fruit flies are an attractive system to quickly and systematically begin to understand how exposure to wildfire impacts health. Flies share 60% genetic homology with humans, they have respiratory systems with some similarities to the human lung, and can be exposed to wildfire smoke through inhalation, the relevant route of exposure in humans.
Our research is highly collaborative
Rigorous investigation requires the use of diverse and complementary perspectives. To make sure our research has the biggest impacts, all of our projects involve close collaborations with national and international research groups. If you are interested in the work we do, reach out, we are love to talk science, share knowledge, and learn from others.
Our work is possible thanks to the support of our funders
|
|
|
|
|
|
