Abhimanyu Amarnani, MD, PhD

New York University Grossman School of Medicine 

Mentor(s): Gregg Silverman, MD and Kelly Ruggles, PhD 

Project Title: Lupus Nephritis: Dysbiosis, Platelet Activity, & Antibody Cross-Reactivity 

About the Researcher 

Dr. Amarnani is a physician-scientist interested in autoimmune diseases, particularly systemic lupus erythematosus (SLE), and is currently based at New York University (NYU). He completed his undergraduate training at the University of California, Los Angeles, where he assessed the utility of mass spectrometry-based proteomics techniques to effectively quantify peptide abundance in formalin-fixed paraffin-embedded kidney tissues. He earned his MD and PhD degrees from SUNY Downstate Health Sciences University, where he elucidated the role of the MiT family of transcription factors in B cell autoreactivity and defined how loss of Mitf function can break B cell tolerance in murine models. At NYU, Dr. Amarnani is mentored by Dr. Silverman and Dr. Ruggles, studying the interplay of gut dysbiosis, platelet activity, and immune regulation in lupus nephritis. Dr. Amarnani is dedicated to a career of translational research, integrating his bench, computational, and clinical knowledge to develop novel treatments to improve outcomes for patients with rheumatic diseases, especially SLE. 

Project Summary 

Our research proposal, "Lupus Nephritis: Dysbiosis, Platelet Activity, & Antibody Cross-Reactivity," aims to understand how changes in gut bacteria contribute to lupus nephritis (LN), a severe kidney complication in systemic lupus erythematosus (SLE). LN affects over half of all SLE patients and presents significant challenges due to its complex causes and limited treatment options. This research focuses on Ruminococcus gnavus (RG) and its surface molecule, lipoglycan (LG), which trigger LN flares in over 40% of affected individuals. The approach integrates a comprehensive investigation into the intricate mechanisms underlying LN pathogenesis driven by RG dysbiosis. 

We will examine distinct whole-blood and isolated platelet gene expression signatures in LN patients with RG blooms and the mechanism of direct kidney damage driven by antibodies targeting RG lipoglycan (LG). By isolating circulating B cells that have B-cell receptors that bind LG in LN patients, we can understand if these same receptors, produced as antibodies, can directly cross react with kidney tissue to drive LN disease. By uncovering these molecular mechanisms, it can demonstrate that subsetting LN patients based on RG blooms could lead to targeted, personalized treatments for patients, either through treatments targeting platelet activity or treatments directly combating RG microbial products.