Moumita Barua, MD

Lay Summary of the Project:

Dr. Barua’s primary research focus is genetic forms of focal and segmental glomerulosclerosis (FSGS). Understanding its genetic causes has advanced our knowledge in the molecular pathogenesis of disease but significant gaps in knowledge still remain. Dr. Barua’s laboratory focuses on developing next-generation sequencing based testing as a diagnostic clinical tool while leveraging it to discover new FSGS genes. Ultimately, her laboratory aims to translate research findings to help guide interpretation of genetic testing in the clinical setting to personalize the care of patients with FSGS in reaching diagnoses, selecting suitable at-risk kidney donors and tailoring treatment options. The laboratory also uses clinically relevant genetic models for mechanistic based studies. Focal and segmental glomerulosclerosis (FSGS) is a disorder that attacks the kidney’s filtering mechanism, called the glomerulus. Diseases of the glomerulus often lead to chronic kidney disease, a major health care problem affecting between 5% and 10% of the adult population in developed countries. In over 50% of FSGS cases, treatment is ineffective in slowing or halting disease. Therapeutic options are limited, in part owing to the poor understanding of its causes. FSGS can be caused by gene mutations. Over the past 20 years, various genetic approaches have identified mutations in over 40 genes as causative or leading to increased susceptibility to FSGS. Mutations in these genes, however, explain only a fraction of cases. Part of this is due to the use of genetic screens that inadequately interrogate all possible genetic causes. There are likely additional, yet undiscovered genes contributing to disease as well. We will use whole genome sequencing to screen known genes in a large well characterized FSGS cohort and to identify novel genes in remaining unexplained cases. It is expected that the genetic epidemiology of FSGS will be accurately ascertained and that new genes causing disease will be discovered. Longitudinal clinical outcomes will be described in genetic cases providing data that will guide the interpretation of the genetic screen in the clinical management of FSGS. Importantly, this work will further our understanding of the molecular basis underlying FSGS, revealing novel targets for therapy.