Ph.D.: Weizmann Institute of Science, Israel
Post-doctorate: Harvard University, USA
Position: Senior Lecturer
Department of Microbiology and Immunology
Faculty of Health Sciences
Novel approaches for the treatment of neurodegenerative and autoimmune diseases
Our laboratory is interested in the characterization of key regulatory factors that maintain immune homeostasis and protection from self-originated neurodegenerative and autoimmune diseases. In contrast to current therapeutics that mostly offer an anti-inflammatory approach, our goals for cure and prevention are aimed at immunotherapy, designed to strengthen endogenous beneficial immune reactions.
Neurodegenerative diseases – Our research is focused on characterizing how immune alterations associated with aging affect neurodegenerative processes like Alzheimer’s disease (AD), studying: a) migration of bone marrow derived cells to the brain; b) cytokines enhancing neuronal recovery; c) the role of brain-specific antibodies entering the brain; d) immune regulation and homeostasis.
These aspects of the immune system can mediate neuronal recovery by affecting the clearance of toxic forms of amyloid from the brain and by inducing a local milieu supportive of neurogenesis. We have developed a unique AD mouse model that lends itself to the development of safe vaccination approaches aimed at prevention and therapy of the disease.
Autoimmunity – Currently, in collaboration with Prof. Smadar Cohen, two approaches are being taken to intervene with the progression of the autoimmune diseases type-1 diabetes and multiple sclerosis, with the aim of enhancing regulatory mechanisms via: a) the use of 3D-scaffolds to generate a transplantable lymphoid-like tissue with local immuno-regulatory properties; b) the use of peptide- or siRNA-containing microparticles to target cells of the immune system, inducing peripheral immunoregulatory properties.
These approaches offer a platform for the design of immune-based therapies to a variety of autoimmune disorders, whether they originate from immune deficient (e.g. cancer, neurodegenerative diseases) or hyper-immune responses (e.g. autoimmune diseases, allergies).
Nemirovsky A., Fisher Y., Baron R., Cohen I.R. and Monsonego A. (2011). Amyloid beta-HSP60 peptide conjugate vaccine treats a mouse model of Alzheimer's disease. Vaccine 29(23):4043-4050.
Fisher Y., Nemirovsky A., Baron R. and Monsonego A. (2011). Dendritic cells regulate amyloid-β-specific T-cell entry into the brain: the role of perivascular amyloid-β. J. Alzheimers Dis. 27(1):99-111.
Abutbul S., Shapiro J., Szaingurten-Solodkin I., Levy N., Carmy Y., Baron R., Jung S. and Monsonego A. (2012). TGF-β signaling through SMAD2/3 induces the quiescent microglial phenotype within the CNS environment. Glia 60(7):1160-1171.
Fisher Y., Strominger I., Biton S., Nemirovsky A., Baron R. and Monsonego A. (2013). Th1 Polarization of T Cells Injected into the Cerebrospinal Fluid Induces Brain Immunosurveillance.
J. Immunol. 192(1):92-102.
Monsonego A., Nemirovsky A. and Harpaz I. (2013). CD4 T cells in immunity and immunotherapy of Alzheimer's disease. Immunology 139(4):438-446.
Harpaz I., Abutbul S., Nemirovsky A., Gal R., Cohen H. and Monsonego A. (2013). Chronic exposure to stress predisposes to higher autoimmune susceptibility in C57BL/6 mice: glucocorticoids as a double-edged sword. Eur. J. Immunol. 43(3):758-769.