Kuti Baruch

Kuti Baruch
ImmunoBrain Checkpoint Ltd., Weizmann Science Park, Ness Ziona, Israel.

PhD

About

47
Publications
12,428
Reads
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5,192
Citations
Additional affiliations
November 2016 - present
ImmunoBrain Checkpoint, Ltd.
Position
  • Head of Department
Description
  • ImmunoBrain Checkpoint, Ltd. is developing a pipeline of disease-modifying immunotherapies for neurological disorders by targeting immune checkpoint pathways.
August 2015 - October 2016
Weizmann Institute of Science
Position
  • Senior Intern
Description
  • Research: (1) PD-1 immune checkpoint blockade as a therapeutic strategy for Alzheimer’s disease. (2) Immunomodulatory approaches in neurological disorders.
August 2014 - August 2015
Weizmann Institute of Science
Position
  • PostDoc Position
Description
  • Neuroimmune crosstalk in neurodegenerative diseases.

Publications

Publications (47)
Article
Full-text available
Systemic immune suppression may curtail the ability to mount the protective, cell-mediated immune responses that are needed for brain repair. By using mouse models of Alzheimer's disease (AD), we show that immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway evokes an interferon (IFN)-γ-dependent systemic immune respons...
Article
Full-text available
Alzheimer's disease (AD) is a neurodegenerative disorder in which chronic neuroinflammation contributes to disease escalation. Nevertheless, while immunosuppressive drugs have repeatedly failed in treating this disease, recruitment of myeloid cells to the CNS was shown to play a reparative role in animal models. Here we show, using the 5XFAD AD mou...
Article
Full-text available
Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)–dependent gene expression profile that was also found in aged human brains. In...
Article
Full-text available
Chronic neuroinflammation is evident in brain aging and neurodegenerative disorders and is often associated with excessive nitric oxide (NO) production within the central nervous system (CNS). Under such conditions, increased NO levels are observed at the choroid plexus (CP), an epithelial layer that forms the blood–cerebrospinal fluid barrier (BCS...
Article
Hippocampal neurogenesis is affected throughout life by factors external to the brain, including what we eat, our gut microbiota, and the immune system. However, the mechanisms that link microbiota to neurogenesis are still puzzling. Now in Cell Reports, Möhle et al. (2016) attribute a role to Ly6C(hi) monocytes in this gut-immune-brain axis.
Article
Full-text available
Microglia and monocyte-derived macrophages (MDM) are key players in dealing with Alzheimer’s disease. In amyloidosis mouse models, activation of microglia was found to be TREM2 dependent. Here, using Trem2−/−5xFAD mice, we assessed whether MDM act via a TREM2-dependent pathway. We adopted a treatment protocol targeting the programmed cell death lig...
Article
The ongoing cross‐talk between the immune system and the central nervous system plays a major role in healthy brain tissue maintenance, with critical implications to brain aging and neurodegeneration. Based on the innovative concept of “protective autoimmunity”, established by Schwartz and her group, it was shown that targeting the programmed cell...
Article
Full-text available
The immune system supports brain plasticity and homeostasis, yet it is prone to changes following psychological stress. Thus, it remains unclear whether and how stress-induced immune alterations contribute to the development of mental pathologies. Here, we show that following severe stress in mice, leukocyte trafficking through the choroid plexus (...
Article
Full-text available
Alzheimer’s disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar e...
Article
Severely stressful conditions can trigger changes in brain homeostasis, yet the underlying mechanism and the implications of this response to post traumatic mental pathologies are not fully understood. Recent findings have shown that different immune system activation profiles can determine the outcome of psychological stress on brain function, and...
Article
Full-text available
During ageing, microglia acquire a phenotype that may negatively affect brain function. Here we show that ageing microglial phenotype is largely imposed by interferon type I (IFN-I) chronically present in aged brain milieu. Overexpression of IFN-β in the CNS of adult wild-type mice, but not of mice lacking IFN-I receptor on their microglia, induces...
Article
Alzheimer’s disease (AD) is a detrimental neurodegenerative disease with no effective treatments. Due to cellular heterogeneity, defining the roles of immune cell subsets in AD onset and progression has been challenging. Using transcriptional single-cell sorting, we comprehensively map all immune populations in wild-type and AD-transgenic (Tg-AD) m...
Chapter
For decades, the brain was considered to be a tissue behind barriers, and thus autonomous with respect to its maintenance needs. Several years ago, our group suggested that the ability of the brain to operate optimally, with relatively little deterioration throughout life, is dependent on continuous support from circulating immune cells. We envisio...
Conference Paper
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with unresolved chronic neuroinflammation. Nevertheless, boosting recruitment of immune cells under chronic neurodegenerative conditions in general, and in AD in particular, was shown to attenuate pathology. Our group recently pointed to the brain’s choroid plexus (CP), as a potent...
Article
Microglia, the resident myeloid cells of the central nervous system, play important roles in life-long brain maintenance and in pathology. Despite their crucial role, their regulatory dynamics during brain development have not been fully elucidated. Genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis thro...
Article
Recent findings have revealed distinct roles for type I and II interferons (IFN-I and IFN-γ) in the recruitment of immune cells to the central nervous system (CNS) and highlighted the importance of this process for brain maintenance and protection/repair. Furthermore, manipulation of IFN-I and IFN-γ pathways in pathological contexts has yielded con...
Conference Paper
Multiple lines of evidence indicate that non-tissue-autonomous factors modulate brain senescence; however, the origin and roles of signals which shape brain’s function in the aged body remain enigmatic. Recent studies identified the brain’s choroid plexus (CP), a ventricular epithelial structure which forms the blood-cerebrospinal fluid-barrier, as...
Article
Full-text available
Amyotrophic lateral sclerosis (ALS) is a devastating fatal motor neuron disease, for which there is currently no cure or effective treatment. In this disease, local neuroinflammation develops along the disease course and contributes to its rapid progression. In several models of CNS pathologies, circulating immune cells were shown to display an ind...
Article
Neuropsychiatric disease is one of the most common manifestations of human systemic lupus erythematosus, but the mechanisms remain poorly understood. In human brain microvascular endothelial cells in vitro, TNF-like weak inducer of apoptosis (TWEAK) decreases tight junction ZO-1 expression and increases the permeability of monolayer cell cultures....
Article
Full-text available
Inflammation is an integral part of the body's physiological repair mechanism, unless it remains unresolved and becomes pathological, as evident in the progressive nature of neurodegeneration. Based on studies from outside the central nervous system (CNS), it is now understood that the resolution of inflammation is an active process, which is depen...
Article
Full-text available
Reduction in T cell receptor (TCR) diversity in old age is considered as a major cause for immune complications in the elderly population. Here, we explored the consequences of aging on the TCR repertoire in mice using high-throughput sequencing (TCR-seq). We mapped the TCRβ repertoire of CD4+ T cells isolated from bone marrow (BM) and spleen of yo...
Article
Full-text available
Infiltrating T cells and monocyte-derived macrophages support central nervous system repair. Although infiltration of leucocytes to the injured central nervous system has recently been shown to be orchestrated by the brain's choroid plexus, the immunological mechanism that maintains this barrier and regulates its activity as a selective gate is poo...
Conference Paper
The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circula...
Article
Full-text available
Adaptive immunity was repeatedly shown to play a role in maintaining lifelong brain function. Under physiological conditions, this activity was associated with CD4(+) T cells specific for brain self-antigens. Nevertheless, direct interactions of T cells with the healthy neuronal parenchyma are hardly detectable. Recent studies have identified the b...
Article
Full-text available
The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circula...
Article
Full-text available
Stressful episodes or chronic stress can shape our brain, leaving behind their biochemical signature on the neural tissue parenchyma. Mitigating such detrimental effects on the central nervous system (CNS) would be advantageous for coping with stress. While the underlying mechanisms that facilitate this response are still a mystery, recent studies...
Article
Full-text available
The ability to respond to a wide range of novel touch sensations and to habituate upon repeated exposures is fundamental for effective sensation. In this study we identified adult spinal cord neurogenesis as a potential novel player in the mechanism of tactile sensation. We demonstrate that a single exposure to a novel mechanosensory stimulus induc...
Article
Full-text available
Multiple studies have reported oligodendrocyte and myelin abnormalities, as well as dysregulation of their related genes, in brains of schizophrenia patients. One of these genes is the myelin-basic-protein (MBP) gene, which encodes two families of proteins: classic-MBPs and golli-MBPs. While the classic-MBPs are predominantly located in the myelin...
Article
Full-text available
Gene expression studies using postmortem human brain tissue are a common tool for studying the etiology of psychiatric disorders. Quantitative real-time PCR (qPCR) is an accurate and sensitive technique used for gene expression analysis in which the expression level is quantified by normalization to one or more reference genes. Therefore, accurate...

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