Dr. Melissa Anslow's laboratory is interested in identifying the roles of microRNAs in lower urinary tract development and disease, with our current focus on vesicoureteral reflux (VUR). Vesicoureteral reflux (VUR), abnormal backflow of urine from the bladder to the kidneys, is associated with urinary tract infections, hypertension, and reflux nephropathy. Reflux nephropathy is the 4th most frequent cause of end-stage renal disease in children, resulting in dialysis and transplant. Thus, it is crucial to better understand the molecular pathogenesis underlying VUR to impact therapies and outcomes.
Published data has shown genomic polymorphisms in select microRNAs (miRNAs) that are associated with VUR in some children, but no causal role is established. miRNAs are small, noncoding RNAs that regulate gene expression post-transcriptionally, and are known to be important in many developmental processes. To date, however, no one has shown that miRNA mutations cause VUR in humans or animal models.
The Anslow Lab has observed abnormally high rates of VUR in a transgenic mouse model with deletion of miRNAs in the mesenchyme of the developing lower urinary tract. There is evidence of abnormal ureteric bud (proximal end becomes the ureter) induction site and subsequent abnormal ureter insertion into the bladder. The lab's current work focuses on identifying molecular mechanisms by which the abnormal ureteric bud and ureter positioning occurs. I am also working to profile the miRNA expression in the mesenchyme of the lower urinary tract and elucidate candidate miRNAs that may be important in lower urinary tract development and prevention of VUR.