PD Dr. Simone Mader

Keywords:
autoantibodies, autoreactive B cells, CNS demyelinating diseases, Cerebellar Ataxia, MOG, AQP4, novel autoantigens

Brief research description:
There is an increasing awareness of the contribution of CNS-reactive antibodies in different neurological diseases. These antibodies penetrate brain tissue upon blood-brain barrier breach or early in development. Antibodies can bind to different extracellular or intracellular antigens and their contribution to tissue injury is often unclear. We aim to characterize novel CNS-reactive antibodies in different autoimmune diseases and analyze the mechanisms of autoantibody-mediated impairment of neuronal or glial cell function. Our studies provide important insights for biomarker discovery and for future therapeutic applications to prevent the pathogenic effects of CNS-reactive autoantibodies.

Current GSN students: Samantha Ho

Selected publications:

1. Mader S, Ho S, Wong H K §, Baier S §, Winklmeier S, Riemer C, Rübsamen H, Fernandez I, Gerhards R , Du C, Chuquisana Omar, Lünemann J, Lux A, Nimmerjahn F, Bradl M*, Kawakami N*, Meinl E* Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein, Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2300648120. doi: 10.1073/pnas.2300648120. Epub 2023 Mar 21.

2. Ho S, Oswald E, Wong HK, Vural A, Yilmaz V, Tüzün E, Türkoğlu R, Straub T, Meinl I, Thaler F, Kümpfel T, Meinl E*, Mader S*. Ocrelizumab Treatment Modulates B-Cell Regulating Factors in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Jan 26;10(2):e200083. doi: 10.1212/NXI.0000000000200083. Print 2023 Mar.

3. Mader S, Brimberg L, Vo A, Strohl JJ, Crawford JM, Bonnin A, Carrión J, Campbell D, Huerta TS, La Bella A, Berlin R, Dewey SL, Hellman M, Eidelberg D, Dujmovic I, Drulovic J, Bennett JL, Volpe BT, Huerta PT, Diamond B. In utero exposure to maternal anti-aquaporin-4 antibodies alters brain vasculature and neural dynamics in male mouse offspring. Sci Transl Med. 2022, 20;14(641):eabe9726. DOI: 10.1126/scitranslmed.abe9726

4. Mader S, Jeganathan V, Arinuma Y, Fujieda Y, Dujmovic I, Drulovic J, Shimizu Y, Sakuma Y, Stern JNH, Aranow C, Mackay M, Yasuda S, Atsumi T, Hirohata S, Diamond B. Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder: Do They Share Common Targets? Arthritis Rheumatol. 2018 Feb;70(2):277-286. DOI: 10.1002/art.40356

5. Brimberg L*, Mader S*, Jeganathan V, Berlin R, Gregersen P, Huerta P, Volpe B, Diamond B. Caspr2-reactive antibody cloned from a mother of an ASD child mediates ASD-like phenotype in mice. Molecular Psychiatry. 2016 Dec;21(12):1663-1671 (* co-first authors) DOI: 10.1038/mp.2016.165