2020 NephCure Award Recipients NEPTUNE Ancillary Studies Grant Awardees ASTRID WEINS, MD, PhD Autoimmunity in Primary or Recurrent Podocytopathies – Clinicopathologic correlation and mechanistic studies Astrid Weins, MD, PhD, is an Associate Pathologist at Brigham and Women’s Hospital in Boston, MA, and an Assistant Professor of Pathology at Harvard Medical School. She is a kidney pathologist attending on the BWH diagnostic renal pathology service since 2011, and also directs an active translational research program studying proteinuric kidney diseases. She has received the 2019 Renal Pathology Society’s Gloria Gallo Research Award for her contributions to understanding podocyte pathobiology and primary podocytopathies, and a 2019 Eleanor and Miles Shore fellowship by Harvard Medical School. Her research focuses on understanding the pathobiology of acute nephrotic syndrome and podocyte injury by integrating morphologic observations with state-of-the-art imaging and tissue interrogation techniques. Lay Summary of the Project: Minimal Change Disease (MCD) and primary/idiopathic FSGS are important pathology diagnoses in adults and children with nephrotic syndrome (NS). Both are characterized by disruption of the filtration slit diaphragm, the final barrier to protein loss formed by specialized kidney cells, the podocytes; hence, we term this group of diseases “podocytopathies”. In contrast to congenital forms, the cause of acquired podocytopathies/NS remains unknown. There is strong evidence pointing to a role of the immune system and a causative factor circulating in the blood; however, its identity has remained elusive. The fact that particular immunosuppressive therapies are often effective in these patients further supports an autoimmune etiology. Our studies in a substantial subset of adult and pediatric MCD patients have led to the discovery of autoantibodies targeting and removing an essential kidney filter protein. In animal models, similar antibodies cause rapid disassembly of the filtration slit diaphragm and, consequently, massive proteinuria. We can detect and quantify those antibodies in the blood using a specific test (ELISA). Based on our findings in MCD, we hypothesize that the same antibodies are also detectable in some NS patients who progress to FSGS and in some who show rapid proteinuria recurrence in the transplant. LAURA MARIANI, MD Immunometabolism and treatment response in FSGS/MCD Dr. Mariani is a nephrologist and researcher at the University of Michigan. She completed her medical school training at the University of Michigan and subsequently completed her internal medicine residency, chief residency, nephrology fellowship, and Masters of Science in Clinical Epidemiology at the University of Pennsylvania. Dr. Mariani is currently an Assistant Professor in the Division of Nephrology at the University of Michigan and has a primary clinical and research interest in observational studies in glomerular disease, including NEPTUNE and CureGN. Her primary research interest is in developing and applying statistical methods for clinical outcome definition and prediction of kidney disease progression as well as linking clinical phenotype to novel biomarkers and high dimensional omics data to better understand disease mechanisms that can be targeted for therapy in glomerular disease. Lay Summary of the Project: The underlying mechanism of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) and factors which determine a patient’s disease trajectory and response to therapy remain unclear. This project will measure products of metabolism in the blood and urine and compare them to kidney biopsy tissue gene expression levels to identify new markers of disease activity and potential targets for therapy. See Awardees From Other Years: 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 2008