Structure-guided design of a targeted autoantibody degrader for neurologic disease
Zimanyi, M., Dayao, M., Asencor, A.I., Kondapavulur, S., Asaki, J., McCutcheon, K., Dabaco, C., Bodansky, A., Craik, C.S., Pleasure, S.J., et al.
Welcome to the Pluvinage Lab!
Our goal is to improve the lives of patients with neurological diseases. We do this by exploring undiagnosed autoimmunity in rare mystery cases and common neurodegenerative conditions alike. How does the immune system regulate cognitive function, and how can we modulate it to promote healthy brain aging?
Research Focus
Autoantibody Discovery and Mechanism
Autoimmune encephalitis (AE) is a rare condition where antibodies target brain antigens leading to severe cognitive dysfunction, but the identity of these antibodies is often unknown. We are developing functional genomic and computational tools to discover the source, target, and mechanism of new pathogenic autoantibodies.
Antigen-Specific Treatments
Current treatments for autoimmune neurological diseases are nonspecific, ineffective, and/or neurotoxic. How can we eliminate pathogenic autoantibodies while leaving the rest of the immune system intact?
Autoimmune Regulation of Cognition
Beyond AE, comorbid autoantibodies are enriched in several neurodegenerative conditions. We investigate the hypothesis that pathogenic autoantibodies exacerbate dementia, and, even more exploratory, that protective autoantibodies exist in cognitively resilient individuals.
Publications
Anti-CD320 autoantibodies and central nervous system vitamin B12 deficiency in idiopathic myelopathy
Pluvinage, J.V., Acero-Garces, D., Greco, G., Moseley, C.E., Sidhu, S., Zorn, K.C., Kondapavulur, S., Richie, M., Douglas, V., Mohan, S., et al.
medRxiv • January 2026
Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency
Pluvinage JV, Ngo T, Fouassier C, McDonagh M, Holmes BB, Bartley CM, Kondapavulur S, Hurabielle C, Bodansky A, Pai V, Hinman S, Aslanpour A, Alvarenga BD, Zorn KC, Zamecnik C, McCann A, Asencor AI, Huynh T, Browne W, Tubati A, Haney MS, Douglas VC, Louine M, Cree BAC, Hauser SL, Seeley W, Baranzini SE, Wells JA, Spudich S, Farhadian S, Ramachandran PS, Gillum L, Hales CM, Zikherman J, Anderson MS, Yazdany J, Smith B, Nath A, Suh G, Flanagan EP, Green AJ, Green R, Gelfand JM, DeRisi JL, Pleasure SJ, Wilson MR.
Science Translational Medicine • June 2024
The CD22-IGF2R interaction is a therapeutic target for microglial lysosome dysfunction in Niemann-Pick type C
John V Pluvinage, Jerry Sun, Christel Claes, Ryan A Flynn, Michael S Haney, Tal Iram, Xiangling Meng, Rachel Lindemann, Nicholas M Riley, Emma Danhash, Jean Paul Chadarevian, Emma Tapp, David Gate, Sravani Kondapavulur, Inma Cobos, Sundari Chetty, Anca M Pașca, Sergiu P Pașca, Elizabeth Berry-Kravis, Carolyn R Bertozzi, Mathew Blurton-Jones, Tony Wyss-Coray
Science Translational Medicine • December 2021
CD22 blockade restores homeostatic microglial phagocytosis in ageing brains
John V. Pluvinage, Michael S. Haney, Benjamin A. H. Smith, Jerry Sun, Tal Iram, Liana Bonanno, Lulin Li, Davis P. Lee, David W. Morgens, Andrew C. Yang, Steven R. Shuken, David Gate, Madeleine Scott, Purvesh Khatri, Jian Luo, Carolyn R. Bertozzi, Michael C. Bassik & Tony Wyss-Coray
Nature • April 2019
Team
Core Investigator
John Pluvinage, MD, PhD
John is an Assistant Professor of Neurology at the University of California, San Francisco. He received his BS in Bioengineering and then MD and PhD from Stanford, investigating mechanisms of microglial aging and rejuvenation. He completed his clinical Neurology residency and postdoctoral fellowship at UCSF focusing on the overlap between autoimmunity and neurodegeneration. His research has been recognized by a Burroughs Wellcome Fund Career Award for Medical Scientists, a NIH K08 Career Development Award, and the American Academy of Neurology’s S. Weir Mitchell Award.
Current Members
Senior Scientist
Natalia Friedland, PhD
Natalia is a Senior Scientist at the Arc Institute with expertise spanning structural biology, vaccine development, and cell therapy. She earned her PhD from UC Berkeley, where she studied protein structure and signaling using X-ray crystallography. As a scientist in the Kim Lab at Stanford, she contributed to vaccine development efforts targeting SARS-CoV-2 and HIV, before going on to lead the molecular assays group at Adicet Bio. In the Pluvinage Lab, she draws on this interdisciplinary background to develop molecular and biochemical tools that rigorously investigate the underexplored role of autoimmune mechanisms in neurological disease and brain aging. Outside the lab, she enjoys traveling, gardening, and hiking.
Graduate Student | Joint with Tony Wyss-Coray
Richard Dela Rosa
Richard is a 1st year Biology PhD student from Stanford. He received his BS in Life Sciences from Ateneo de Manila University (Philippines). He completed his MSc in Molecular Mechanisms at Radboud University (Netherlands), including an internship at Boston Children's Hospital where he developed VHH tools to dissect the basic mechanisms of E2 ubiquitin-conjugating enzymes. Before starting graduate school, he worked at Cradle, a techbio start-up based in the Netherlands, to build high-throughput workflows to characterize and optimize antibody fragments. Outside of work, he enjoys painting, hiking, and reading.
Postdoc
Marcell Zimanyi, PhD
Marcell earned his PhD at UC San Francisco in Yifan Cheng’s lab where he revealed a regulatory structural element in herpesvirus proteases. During his postdoctoral work in Charly Craik’s lab at UCSF, he characterized autoimmune responses in recurrent kidney disease and solved the structure of a patient-derived anti-CD320 autoantibody in complex with its epitope. Before his academic endeavors, Marcell worked at Bayer in the hematology group to develop antibody-based therapies for non-malignant bleeding disorders. Outside the lab, Marcell likes to play table tennis, dine at fun restaurants, and tend to his houseplants.
Collaborator
Sravani Kondapavulur, MD, PhD
Sravani received her undergraduate degree in biomedical engineering at UC Berkeley, followed by a research gap year at UCSF with Dr. Steven Hetts designing endovascular interventional devices for chemotherapy filtration from the blood. Afterwards, she attended the Medical Scientist Training Program at UCSF, where she completed a PhD in Bioengineering and received an NINDS F31 grant to study multi-brain region coordination of movement in healthy and stroke rodents for neuromodulation design in Karunesh Ganguly's lab. She then joined UCSF’s neurosurgery residency program, and looks forward to engineering surgical and therapeutic solutions for the variety of neurological disorders. In her free time, she enjoys figure skating, running marathons, and playing with the postdog Berkeley.
Postdog
Berkeley
Berkeley received his BA in human psychology from San Jose State University before completing his PhD on sleep electrophysiology from Stanfur. In his free time, he enjoys chasing squirrels and chewing on milk cartons.
Contact Us
For prospective postdocs, scientists, and research associates, please visit arcinstitute.org/jobs to apply for openings. For prospective students, please contact me directly at [email protected].
