Prof. Alon Monsonego

Research Field

Immune cells begin to populate the central nervous system (CNS) as early as during embryonic development. Cells, termed microglia, become permanent residents of CNS tissues, where they serve a variety of functions, such as clearance of pathogens and regulation of neuronal function. The Monsonego group addresses questions related to the unique differentiation process of microglia following their entry into the CNS, as well as their impact on chronic diseases of the brain, such as epilepsy, multiple sclerosis, and Alzheimer’s disease. Chronic mild stress alters the homeostatic functioning of the immune system by altering cellular responses to glucocorticoids. Such immune regulation imbalance can subsequently lead to a predisposition to chronic illnesses or to the intensification of such chronic illnesses, such as depression, autoimmunity, and neurodegenerative diseases. These effects are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, a complex network linking the nervous, endocrine, and immune systems. Work by the Monsonego laboratory addresses the regulatory role of glucocorticoids in lymphocyte subsets and asks how such regulation is impaired following chronic stress or chronic inflammation.

Alzheimer’s disease is characterized by enhanced degeneration processes in the aging brain which lead to cognitive decline and dementia. The goal of Prof. Monsonego and his team is to reveal mechanisms of leukocyte dysregulation with aging that contribute to Alzheimer’s disease pathogenesis. Based on these studies, Prof. Monsonego and his colleagues are developing prophylactic and therapeutic immune-based approaches applicable to a variety of age-related disorders. Although the etiology of autoimmune diseases remains largely unknown, it is becoming clear that a loss in immune regulation results in pathogenic stimulation of autoreactive lymphocytes which otherwise are kept quiescent. Once such pathogenic stimulation of lymphocytes occurs, these cells renew and continuously attack the body.

Ongoing research being conducted in collaboration with Prof. Smadar Cohen is aimed at generating transplantable lymphoid-like scaffolds which functionally re-educate pathogenic T cells so as to allow long-term graft survival, as well as tissue regeneration.