Genomics of Rare Genetic Disease, Medical Genomics, Genetic Modifiers, Model Organisms, Whole Genome Sequencing/Bioinformatics
My research program uses multidisciplinary approach (human and model organism genomics; ‘wet’ and ‘dry’ lab approaches) to understand the rare disease genomics. Rare diseases are typically monogenic and individually very rare but collectively affect at least 1 in 50 individuals. The recent advances (less than a decade old) in high throughput sequencing technology (HTPS) have revolutionized diagnosis and discovery of novel rare disease genes by enabling the entire genome (whole genome sequencing, WGS) or a protein-coding portion (whole exome sequencing, WES) to be read in a single test. My group has three main research interests:

Diagnostic potential of HTPS
Unlike exome sequencing, genome sequencing has the potential to detect all classes of genetic variation of an individual in one experiment. One goal of my research program is to further improve the detection and interpretation of an entire spectrum of genetic variation in a genome using HTPS. Together with novel gene-disease associations, this can improve diagnostic efficiency.

Phenotypic variability in rare diseases
Incomplete penetrance and variable expressivity make it difficult to determine accurate prognosis of disease progression and expected outcome. Although the extent of both remains largely unknown for rare disease, recent large-scale sequencing projects (thousands of ‘healthy’ people sequenced) and data aggregation consortia allow us to assess the phenotypic variability in rare disease.

Genetic Modifiers
The ultimate goal of my research program is to understand why two individuals with the same rare disease-causing variant may have different clinical presentation of the disease (severe-milde-none)? In other words, we are asking whether other variants in a genome exist that may alleviate or exacerbate the severity of the disease-causing variant. To reach this goal, we combine an elegance of <i>Caenorhabditis elegans’</i> genetics/genomics with human genomics (e.g. discordant siblings), as well as the above noted advances in variant detection/interpretation and data aggregation. <i><b>Genetic modifiers are super cool</b></i> as they teach us about biological networks of human disease genes and may provide a clue for better therapeutics design.