Michal Schwartz (; born 1 January 1950) is a professor of neuroimmunology at the

Weizmann Institute of Science The Weizmann Institute of Science ( ''Machon Weizmann LeMada'') is a Public university, public research university in Rehovot, Israel, established in 1934, fourteen years before the State of Israel was founded. Unlike other List of Israeli uni ...

. She is active in the field of

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s, particularly utilizing the immune system to help the brain fight terminal neurodegenerative brain diseases, such as

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

and

dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

. Schwartz's studies have shown that the immune system supports a healthy brain's function and is vital for healing and protecting the brain in case of injury or disease. Schwartz coined the term protective autoimmunity and discovered roles for

immune cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

in repair and

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

. She has been the elected chair of the International Society of Neuroimmunology (ISNI) since 2016. In 2023 Schwartz received the honorary Israel Prize for Life Sciences.

Education

Schwartz gained her Bachelor of Science in chemistry at the

Hebrew University of Jerusalem The Hebrew University of Jerusalem (HUJI; ) is an Israeli public university, public research university based in Jerusalem. Co-founded by Albert Einstein and Chaim Weizmann in July 1918, the public university officially opened on 1 April 1925. ...

in 1972. She received her Ph.D. in immunology in 1977 at the

, where she would later spend the majority of her career. She also spent time at the

University of Michigan The University of Michigan (U-M, U of M, or Michigan) is a public university, public research university in Ann Arbor, Michigan, United States. Founded in 1817, it is the oldest institution of higher education in the state. The University of Mi ...

, Ann Arbor, researching nerve regeneration.

Career and research

At the Weizmann Institute, she progressed from senior scientist in the Department of Neurobiology to full professor in 1998, and was then awarded the Maurice and Ilse Katz Professorial Chair in Neuroimmunology in 2016. Schwartz's work in neuroimmunology has encompassed a wide range of pathologies in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS), including injury, neurodegeneration, mental dysfunction, and aging. She coined the term protective autoimmunity and demonstrated the role of

such as

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

and

T cells T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

repair. She also identified specific brain areas for 'cross talk' between the CNS and the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

. This cross-talk is important for recruiting immune cells and maintaining a healthy brain, and the disruption of this cross-talk can play a role in brain aging and

. She also showed this role in pregnancy and fetal

brain development The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special sens ...

, where immune disruption in the mother can be linked to

neurodevelopmental disorders Neurodevelopmental disorders are a group of mental conditions negatively affecting the development of the nervous system, which includes the human brain, brain and spinal cord. According to the American Psychiatric Association Diagnostic and Sta ...

in their children. Another focus of her work has been on repurposing cancer immunotherapies such as

PD-1 Programmed cell death protein 1 (PD-1), (CD279 cluster of differentiation 279). PD-1 is a protein encoded in humans by the ''PDCD1'' gene. PD-1 is a cell surface receptor on T cells and B cells that has a role in regulating the immune system's re ...

blockers to treat neurodegenerative disorders, such as

Macrophages

The Schwartz team discovered that bone marrow-derived macrophages are needed for central nervous system (CNS) repair. The brain-resident myeloid cells (the microglia), and infiltrating monocyte-derived macrophages are not redundant populations, despite their myeloid

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...

, and display distinct functions in resolution of brain inflammation.

Autoimmunity

In her research, Schwartz discovered that the ability to cope with sterile CNS injuries requires support in the form of an adaptive immune response mediated by CD4+ T cells that recognize CNS antigens. She coined the concept of protective autoimmunity, to distinguish this response from autoimmune disease, in which the anti-self response escapes control. Over the years, it became clear that adaptive immunity is needed to facilitate the recruitment of immunoregulatory cells, including bone marrow-derived macrophages and FoxP3 regulatory T cells, though the balance between regulatory T cells and effector memory cells is different in the periphery versus the brain.

Brain Homeostasis

Schwartz’s team discovered the role of adaptive systemic immune cells, and specifically T cells recognizing brain antigens (Protective autoimmune T cells), in supporting the cognitive capacity of the healthy brain, for lifelong

, and functional

brain plasticity Neuroplasticity, also known as neural plasticity or just plasticity, is the ability of neural networks in the brain to change through growth and reorganization. Neuroplasticity refers to the brain's ability to reorganize and rewire its neural ...

. These observations paved the way for numerous additional discoveries in which the brain-immune axis was described.

The Choroid Plexus

Schwartz’s team identified the brain’s choroid plexus (CP) within the blood-cerebrospinal fluid barrier as an immunological interface between the brain and the immune system. It serves as a niche that hosts immune cells, and as a physiological entry gate for

leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

. Focusing on this unique niche within the brain led the Schwartz group to propose that IFN-γ holds the key to regulating CP gateway activity. Her team further showed that in brain aging and neurodegenerative diseases (studied using both mouse models and human samples), dysfunction of this interface is determined both by signals originating in the brain, and signals from the aged immune system, which led to the identification of Type-I Interferon (IFN-I) at the CP as a negative player, affecting the fate of the aging brain in general, and of microglia, in particular. A similar IFN-I signature at the CP was subsequently discovered by others in Alzheimer’s disease and in the postmortem brains of infected patients who died from COVID-19.

Immunotherapy

The discovery that adaptive immunity plays a key role in brain function and repair, the need for bone marrow-derived macrophages to resolve local brain inflammation, the fact that

(AD) and all forms of dementia are mainly age-related diseases, and the fact that the immune system is particularly affected by aging all led Schwartz to propose a new treatment for combating dementias. Schwartz suggested empowering systemic immunity, using a form of

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

by modestly blocking the inhibitory immune checkpoint PD1/PD-L1 pathway. This treatment drives an immune-dependent cascade of events, that allows the harnessing of bone marrow-derived macrophages and regulatory T cells to help clear toxic factors from the diseased brain, and to arrest the local inflammation, thereby providing a comprehensive multi-factorial therapy through modification of multiple elements that go awry in AD. Schwartz’s patents for developing such immunotherapy for AD are licensed to a small Biopharma company, Immunobrain Checkpoint. The company is awaiting a clinical trial in AD patients, supported in part by the National Institute of Aging, the US National Institutes of Health, and The Alzheimer's Association.

Students

Schwartz has mentored approximately 40 Ph.D. students , and approximately 39 MSc students. Her former Ph.D. students include Jonathan Kipnis, Noga Ron Harel, Jasmin Fisher, Asya Rolls.

References

{{DEFAULTSORT:Schwartz, Michal Women immunologists Academic staff of Weizmann Institute of Science Weizmann Institute of Science alumni 1950 births Academics from Tel Aviv Hebrew University of Jerusalem alumni University of Michigan alumni Israeli immunologists Israeli neuroscientists Living people