An essential subset of our genetic material lives inside the mitochondria, which is an organelle central to cellular function. ​Mitochondrial genome variation is linked to a range of phenotypes, including rare and common diseases. Despite its importance in health and disease, the functional and clinical impact of most mitochondrial variants remains unknown. Furthermore, the toolkit for analyzing mitochondrial variants lags behind that available for the nuclear genome. We want to help change this.
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Our research mission is to help realize the promise of genomic medicine for all by promoting a holistic approach to human genetics that includes both mitochondrial and nuclear genomes. To do this, we will use computational and experimental methods to advance our understanding of which mitochondrial genomes impact health and disease, and the circumstances in which they have functional and phenotypic consequences. This work is important to enable accurate prediction of disease risk from our entire genome. 

The Lake Lab will initially focus on the following research arms to better understand how our genomes underlie health and disease:

Characterizing genetic variation
​in the population

Analyses of population genetic variation are important for identifying functional variants that underlie disease. The growing availability of sequencing data from diverse populations, tissues, and cell types provides an exciting opportunity for discoveries. ​
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We use innovative methods to analyze mitochondrial and nuclear genomes across populations to reveal new insights into genetic diversity, mutation, and selection within mitochondria. ​This work lays a foundation for improved variant classification and discovery.

​Improving variant classification
​in the mitochondria​​​

Identifying which genetic variants cause disease, a process called variant classification, is a key challenge in human genetics. ​​The toolkit for mitochondrial genome analysis lags behind that for the nuclear genome, hampering the discovery of variation underlying disease. 
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​​We will address this critical challenge by developing methods and resources to help answer the question - which mitochondrial genome variants are deleterious? Specifically, we'll work towards a framework that can provide computational and functional variant annotations.

Discovering causes of disease
& ​their modifiers

Variation in the mitochondrial genome is increasingly being recognized as an important contributor to disease. We'll utilize growing healthcare and genomics datasets and cutting-edge methods, including our own, to shed new light on the role of mitochondrial variation in disease. 

Modifiers alter the phenotypic outcome of genetic variants; understanding these will also be key for accurate prediction of disease risk. In parallel, we aim to identify and characterize modifiers of mitochondrial variants, across heteroplasmy, genetic backgrounds, and other factors. 

Collectively, these research arms aim to advance our understanding of how genetic variation impacts health and disease, across the human population