Curriculum Vitae
I was born in Rehovot, Israel, and raised in the northern Israeli coastal town of Nahariya. After graduating high school, I joined the Israel Defense Forces, initially serving as a pianist in the Southern Command Entertainment Band, and later as an officer in the Educational Corps. I pursued higher education at Haifa University, earning a Bachelor’s degree in Psychobiology, and later obtained an M.Sc. in Physiology from the Technion - Israel Institute of Technology. I completed my Ph.D. in Neuroscience under the guidance of Prof. John C. Liebeskind at the University of California, Los Angeles (UCLA). Following a two-year postdoctoral fellowship at the Cousins Center for Psychoneuroimmunology at UCLA, I returned to Israel in 1990 and joined the Department of Psychology at the Hebrew University of Jerusalem, where I was appointed Full Professor in 2003. I am happily married to Professor Nurit Yirmiya and am the proud father of four children and grandfather to three granddaughters.
In the early 1990s, my initial studies demonstrated that psychoactive drugs, particularly alcohol and opiates, modulate immune function and resistance to cancer through brain-to-immune communication pathways (Yirmiya, R. & Taylor, A. N. (Eds.), Alcohol, Immunity and Cancer. CRC Press, 1993; Nature Medicine,1996). After establishing my laboratory in Jerusalem, I shifted focus to the implications of immune-to-brain signaling. Using animal models across various infectious, autoimmune, and neurological diseases, I delineated the relationship between brain inflammatory cytokines and sickness behavior symptoms.
I am particularly recognized for providing the first experimental evidence linking immune activation to major depression (Brain Research, 1996; Molecular Psychiatry, 1999; Neuropsychopharmacology, 2001). This contribution was highlighted in a historical review by Robert Dantzer and Keith Kelly, stating, "Raz Yirmiya was the first psychobiologist to draw the analogy between sickness behavior and depression. He demonstrated that rats treated with cytokines are less sensitive to the rewarding properties of saccharin solutions or the presentation of a sexually-active partner. Some of these deficits can be mitigated by chronic but not acute administration of antidepressant drugs, which have little or no beneficial effects on sickness behavior" (Brain, Behavior and Immunity, 2007). In parallel, my research group employed controlled and prospective experimental models in humans, showing that immune challenges like endotoxin administration, rubella vaccination, or minor surgery can induce cytokine-mediated disturbances in behavioral, emotional, and cognitive functions (JAMA Psychiatry, 2001). Collectively, these studies have significantly contributed to novel conceptualizations and the development of clinically effective treatments for inflammation-associated major depression.
In our subsequent research, my team and I have revealed that microglial cells and pro-inflammatory cytokines play essential roles in normal physiological neurobehavioral processes, including hippocampal-dependent memory consolidation, neural plasticity, and neurogenesis, with modulation by environmental enrichment (Journal of Neuroscience, 2009; Brain, Behavior and Immunity, 2011; eLife, 2017). Conversely, we found that structural and functional abnormalities in microglial cells, coupled with pathologically elevated levels of the inflammatory cytokine interleukin-1, are implicated in the cognitive deficits and reduced neurogenesis associated with stress-related conditions and neurodegenerative diseases (Frontiers in Neuroendocrinology, 2009; Neuropsychopharmacology, 2014).
Importantly, our studies have shown that stress—a common precursor to depression—triggers significant changes in the structure and function of microglial cells, which play a causal role in the development of depressive-like symptoms. We observed that while initial stress responses activate microglia, chronic, prolonged stress leads to their exhaustion and damage, thereby exacerbating depressive symptoms (Molecular Psychiatry, 2014, 2022). This cyclical pattern of activation and degeneration within microglia mirrors the progressive nature of depression (TINS, 2015).
Recent investigations in my laboratory have demonstrated that early intervention with anti-inflammatory treatments can prevent stress-induced microglial alterations and the onset of depressive-like behaviors. However, these treatments become less effective once microglial degeneration is established. This finding has redirected my laboratory's research focus towards compounds that promote microglia activation, which exert antidepressant effects, possibly by enhancing hippocampal neurogenesis—a principal mechanism of many antidepressants. Current efforts are concentrated on exploring the antidepressant effects of direct microglia stimulators, such as M-CSF or GM-CSF, as well as the effects of immune/microglial checkpoint inhibitors. Our research reveals that chronic stress upregulates several immune checkpoint receptors, such as lymphocyte-activation gene-3 (LAG3). Blocking LAG3, either through electroconvulsive therapy (ECT) or specific antibodies, has shown promising antidepressant outcomes (Rimmerman et al., 2022). Additionally, we are investigating the role of CX3CR1, another checkpoint receptor exclusively expressed by microglia, in stress resilience and depression (Rimmerman et al., 2017; Yirmiya, 2023).
Over the past three decades, my research has yielded some of the most significant insights into the inflammation-depression nexus, advancing our understanding of the disease's origins and the complex mechanisms driving it (Brain, Behavior and Immunity, 2024). Moving forward, my focus will be on using this accumulated knowledge to accelerate the development of innovative antidepressant therapies targeting inflammatory processes. Given that both activation and suppression of the immune system—particularly of microglia—can lead to depressive symptoms, it is clear that depression cannot be effectively managed with a one-size-fits-all approach. Instead, there is a pressing need to shift toward personalized medicine. This would entail precise diagnostic assessments of an individual's inflammatory state, followed by customized treatment plans that fine-tune the immune response through targeted antidepressant therapies. Adopting this tailored approach promises hope to millions who find little relief in standard therapies.