Lauren Baker

Dr. Baker is an Assistant Scientist in the School of Veterinary Medicine and the Department of Urology, School of Medicine and Public Health. Her mentors are Dr. Corinne Engelman and Dr. Stephen Nakada.

The title of Dr.Baker’s research is Discovering genetic drivers of calcium oxalate urinary stone disease through multi-omics dissection in the spontaneous dog model. Kidney stone disease is a common, life-altering diagnosis causing significant patient morbidity. Over 75% of kidney stones are composed of calcium oxalate (CaOx), and recurrence is common. Genetic predisposition plays a large role in disease initiation. The complexity of the disease and human genetic diversity have limited the success of genetic studies in human beings.

The Miniature Schnauzer dog is an excellent spontaneous animal model for genetic study of CaOx urinary stones. Miniature Schnauzers are 12 times more likely to develop CaOx stones compared to the general canine population, and reduced genetic diversity within the breed increases statistical power to detect genetic associations. Previous epidemiological research shows that the majority of Miniature Schnauzers with CaOx stones are hypercalciuric, which is the most common metabolic abnormality in humans. One third of these dogs also have disorders of vitamin D metabolism, indicating that there are multiple drivers of hypercalciuria within the breed. Therefore, the dog model provides the advantage of reduced genetic complexity while maintaining disease complexity that is applicable to the human condition.

Aim 1 of Dr. Baker’s work will pursue the complexity of CaOx stone disease through metabolomics analysis to define molecular phenotypes before genetic association analysis to discover genetic drivers of metabolic abnormalities. Aim 2 will follow up on preliminary evidence that a long intergenic non-coding RNA (lincRNA) is driving regulation of the calcium sensing receptor (CASR), causing absorptive hypercalciuria in stone formers. This work will expand this analysis to discover additional RNA biomarkers, and utilize network analysis to define core genes and genetic pathways that are involved in disease pathogenesis. A similar RNA sequencing analysis in human beings will be performed to construct a consensus network to formally define genes and genetic pathways that are shared between dogs and humans, which will guide future research.