I am a PhD student working under the supervision of Prof Mark McCarthy and Prof Anna Gloyn at the Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM). My research focuses on building high-throughput functional genomic assays to aid in the interpretation of sequence variants, particularly in the clinical diagnostic setting. As next generation sequencing (NGS) becomes more routine clinical practice, we need robust technologies that allow us to reliably interpret the functional consequences of known and novel sequence variants at scale and speed. I am currently addressing this challenge in clinical genomics for individuals who harbour variants in HNF1A: a medically actionable gene and a key player in diabetes pathogenesis. Depending on frequency, penetrance and functional impact, heterozygous variants in HNF1A cause Maturity Onset Diabetes of the Young (MODY), and/or increase Type 2 Diabetes (T2D) risk. An accurate molecular diagnosis for HNF1A variant carriers is important because it influences treatment and informs prognosis. As such, I aim to a) annotate the function of every possible single amino acid substitution in HNF-1a, en masse, using a high-throughput saturation mutagenesis screening approach, b) define the clinical relevance of these data by mapping variant effects on molecular function with phenotypic outcome using multiple complementary in silico, clinical, functional, and biochemical datasets, and c) model these data in the form of a multivariate clinical diagnostic tool for HNF1A variant carriers. Before joining the Gloyn/McCarthy group, I worked as a Research Assistant in a cytogenomics research laboratory led by Prof Cynthia Morton at Harvard Medical School/Brigham and Women's Hospital where I was involved in a large gene mapping and discovery effort known as the Developmental Genome Anatomy Project (DGAP). In 2013, I graduated Phi Beta Kappa, magna cum laude from Wellesley College with a BA in Biological Sciences and Anthropology. Beyond genetics, my research interests include examining cultural perceptions of health and illness, the intersection of faith and science, and gender and leadership.
When is it MODY? Challenges in the Interpretation of Sequence Variants in MODY Genes
Althari S and Gloyn AL, (2016), Rev Diabet Stud, Fall-Winter;12(3-4):330-48