Michal Schwartz (born 1 January 1950) is a professor of

Neuroimmunology Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system. Neuroimmunologists seek to better understand the interactions of these two complex systems during development, home ...

at the

Weizmann Institute of Science The Weizmann Institute of Science ( he, מכון ויצמן למדע ''Machon Vaitzman LeMada'') is a public research university in Rehovot, Israel, established in 1934, 14 years before the State of Israel. It differs from other Israeli unive ...

and is internationally acclaimed as a path-breaking scientist in the study of Neuro-immunology, introducing the dialogue between the immune system and the brain as a novel and pivotal player in life-long brain function and repair. Prof. Michal Schwartz's groundbreaking discovery has revolutionized the field of neurodegenerative diseases, and led to a transformation in searching treatments for

neurodegenerative diseases A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

, Her immunotherapeutic approach to treating of harnessing the immune system to help the brain to treat terminal neurodegenerative brain diseases such as

Alzheimer's Disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and

Dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

, is currently in the expedite process of development. In her studies, she has shown, against prevailing wisdom at the time, 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's research has not only changed the accepted scientific dogma but laid the foundation worldwide for developing new research and treatment approaches in the field of brain disease and neurodegenerative conditions, particularly Alzheimer's Disease and Dementia. She discovered new roles for

immune cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

in repair and

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

, coined the term " Protective autoimmunity" and expanded the field of

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...

neuroscience Neuroscience is the scientific study of the nervous system (the brain, spinal cord, and peripheral nervous system), its functions and disorders. It is a multidisciplinary science that combines physiology, anatomy, molecular biology, development ...

. She has been the elected chair of the International Society of Neuroimmunology (ISNI) since 2016, and her book "Neuroimmunity: A New Science that Will Revolutionize How We Keep Our Brains Healthy and Young" received an honorable mention for the 2016

PROSE Awards The PROSE Awards (Professional and Scholarly Excellence) are presented by the Association of American Publishers’ (AAP) Professional and Scholarly Publishing (PSP) Division. Presented since 1976, the awards annually recognize distinguished prof ...

, Biomedicine & Neuroscience category. Her

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines. Released in beta in November 2004, the Google Scholar index includes p ...

Citation Index is 113.

Education

Schwartz gained her Bachelor of Science (''with distinction'') in chemistry at the

Hebrew University of Jerusalem The Hebrew University of Jerusalem (HUJI; he, הַאוּנִיבֶרְסִיטָה הַעִבְרִית בִּירוּשָׁלַיִם) is a public research university based in Jerusalem, Israel. Co-founded by Albert Einstein and Dr. Chaim Weiz ...

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 , mottoeng = "Arts, Knowledge, Truth" , former_names = Catholepistemiad, or University of Michigania (1817–1821) , budget = $10.3 billion (2021) , endowment = $17 billion (2021)As o ...

, Ann Arbor, researching nerve regeneration.

Career and research

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

neuroimmunology Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system. Neuroimmunologists seek to better understand the interactions of these two complex systems during development, home ...

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 and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

(CNS) including injury, neurodegeneration, mental dysfunction, and aging. By researching the immune system and its interactions with the brain, Schwartz focuses on improving repair, regeneration, and

neuroplasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of Neural circuit, neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that diffe ...

in health and disease. She coined the term " protective autoimmunity' and demonstrated the role of

such as

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

and

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 re ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...

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 processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

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

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

. She also showed this role in pregnancy and fetal

brain development The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...

, where immune disruption in the mother can be linked to

neurodevelopmental disorders Neurodevelopmental disorders are a group of disorders that affect the development of the nervous system, leading to abnormal brain function which may affect emotion, learning ability, self-control, and memory. The effects of neurodevelopmental ...

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

PD-1 Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein on the surface of T and B cells that has a role in regulating the immune system's response to the cells of the human body by down-regula ...

blockers to treat neurodegenerative disorders such as

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

Macrophages

The Schwartz team was the first to discover that bone marrow-derived macrophages are needed for central nervous system (CNS) repair. Thus, her group not only reversed a long-held dogma that immune cells are detrimental to brain function but also established the role of novel participants in CNS repair never considered previously. They further demonstrated that the brain-resident myeloid cells (the microglia), and infiltrating monocyte-derived macrophages are not redundant populations, despite their myeloid phenotype, and display distinct functions in resolution of brain inflammation. These findings completely changed the understanding of the role of bone marrow-derived macrophages in containing brain diseases, to the extent that the current question is no longer whether bone marrow-derived macrophages are needed for brain repair, but how to safely recruit them, and elucidating the routes of their physiological entry to the brain. * Rapalino, O.,O. Lazarov-Spiegler, E. Agranov, G. J. Velan, E. Yoles, M. Fraidakis, A. Solomon, R. Gepstein, A. Katz, M. Belkin, M. Hadani, M. Schwartz. "Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats." ''Nat Med'' 4, no. 7 (Jul 1998): 814-21. * Shechter, R.,A. London,C. Varol, C. Raposo, M. Cusimano, G. Yovel, A. Rolls,M. Mack,S. Pluchino, G. Martino, S. Jung, M. Schwartz. "Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice." ''PLoS Med'' 6, no. 7 (Jul 2009): e1000113. * Shechter, R.,O. Miller,G. Yovel, N. Rosenzweig,A. London, J. Ruckh, K. W. Kim,E. Klein,V. Kalchenko, P. Bendel, S. A. Lira, S. Jung,M. Schwartz. "Recruitment of beneficial M2 macrophages to the injured spinal cord is orchestrated by remote brain choroid plexus." ''Immunity'' 38, no. 3 (Mar 21, 2013): 555-69.

Autoimmunity

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. * Moalem, G.,R. Leibowitz-Amit, E. Yoles, F. Mor, I. R. Cohen, M. Schwartz. "Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy." ''Nat Med'' 5, no. 1 (Jan 1999): 49-55. * Yoles, E.,E. Hauben, O. Palgi, E. Agranov, A. Gothilf, A. Cohen, V. Kuchroo, I. R. Cohen, H. Weiner, M. Schwartz. "Protective autoimmunity is a physiological response to CNS trauma." ''J Neurosci'' 21, no. 11 (Jun 1 2001): 3740-8. * Hauben, E.,E. Agranov, A. Gothilf, U. Nevo, A. Cohen, I. Smirnov, L. Steinman, M. Schwartz. "Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease." ''J Clin Invest'' 108, no. 4 (Aug 2001): 591-9.

Brain Homeostasis

Schwartz’s team discovered the unexpected 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. These seminal observations paved the way for numerous additional discoveries in which the brain-immune axis were described. * Kipnis, J.,H. Cohen,M. Cardon, Y. Ziv, M. Schwartz. "T cell deficiency leads to cognitive dysfunction: implications for therapeutic vaccination for schizophrenia and other psychiatric conditions." ''Proc Natl Acad Sci U S A'' 101, no. 21 (May 25, 2004): 8180-5. * Ziv, Y.,N. Ron,O. Butovsky, G. Landa, E. Sudai, N. Greenberg, H. Cohen,J. Kipnis, M. Schwartz. "Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood." ''Nat Neurosci'' 9, no. 2 (Feb 2006): 268-75. * Baruch, K.,A. Deczkowska, E. David,J. M. Castellano, O. Miller,A. Kertser, T. Berkutzki, Z. Barnett-Itzhaki, D. Bezalel, T. Wyss-Coray, I. Amit, M. Schwartz. "Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function." ''Science'' 346, no. 6205 (Oct 3 2014): 89-93.

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, serving as a niche that hosts immune cells, and as a physiological entry gate for leukocytes. 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. * Shechter, R.,O. Miller,G. Yovel, N. Rosenzweig, A. London, J. Ruckh, K. W. Kim, E. Klein, V. Kalchenko, P. Bendel, S. A. Lira, S. Jung, M. Schwartz. "Recruitment of beneficial M2 macrophages to the injured spinal cord is orchestrated by remote brain choroid plexus." ''Immunity'' 38, no. 3 (Mar 21, 2013): 555-69. * Kunis, G.,K. Baruch, N. Rosenzweig, A. Kertser, O. Miller, T. Berkutzki, M. Schwartz. "IFN-gamma-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair." ''Brain'' 136, no. Pt 11 (Nov 2013): 3427-40. * Baruch, K.,A. Deczkowska, E. David, J. M. Castellano, O. Miller, A. Kertser, T. Berkutzki, Z. Barnett-Itzhaki, D. Bezalel, T. Wyss-Coray, I. Amit, M. Schwartz. "Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function." ''Science'' 346, no. 6205 (Oct 3, 2014): 89-93. * Deczkowska, A.,O. Matcovitch-Natan, A. Tsitsou-Kampeli, S. Ben-Hamo, R. Dvir-Szternfeld, A. Spinrad, O. Singer, E. David, D. R. Winter, L. K. Smith, A. Kertser, K. Baruch, N. Rosenzweig, A. Terem, M. Prinz, S. Villeda, A. Citri, I. Amit, M. Schwartz. "Mef2C restrains microglial inflammatory response and is lost in brain aging in an IFN-I-dependent manner." ''Nat Commun'' 8, no. 1 (Sep 28, 2017): 717.

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. The development of therapies that directly target the peripheral immune system is likely to herald a new era in the desperate search for a treatment for AD and other neurodegenerative diseases. Schwartz’s patents for developing such immunotherapy for AD are licensed to a small Biopharma company, Immnobrain 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. * Baruch, K.,A. Deczkowska, N. Rosenzweig, A. Tsitsou-Kampeli, A. M. Sharif, O. Matcovitch-Natan, A. Kertser, E. David, I. Amit, M. Schwartz. "PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease." ''Nat Med'' 22, no. 2 (Feb 2016): 135-7. * Schwartz, M. "Can immunotherapy treat neurodegeneration?" ''Science'' 357, no. 6348 (Jul 21, 2017): 254-55. * Rosenzweig, N.,R. Dvir-Szternfeld, A. Tsitsou-Kampeli, H. Keren-Shaul, H. Ben-Yehuda, P. Weill-Raynal, L. Cahalon, A. Kertser, K. Baruch, I. Amit, A. Weiner, M. Schwartz. "PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model." ''Nat Commun'' 10, no. 1 (Jan 28, 2019): 465. * Ben-Yehuda, H.,M. Arad, J. M. Peralta Ramos, E. Sharon, G. Castellani, S. Ferrera, L. Cahalon, S. P. Colaiuta, T. M. Salame, M. Schwartz. "Key role of the CCR2-CCL2 axis in disease modification in a mouse model of tauopathy." ''Mol Neurodegener'' 16, no. 1 (Jun 25, 2021): 39. * Dvir-Szternfeld R, Castellani G, Arad M, Cahalon L, Phoebeluc Colaiuta S, Keren-Shaul H, Croese T, Ulland T, Colonna M, Weiner A, Amit I, Schwartz M'. 2021. TREM2-independent neuroprotection is mediated by monocyte-derived macrophages in a mouse model of Alzheimer’s disease Nature Aging,

Students

Schwartz has mentored approximately 40 Ph.D students (12 of whom received recognition awards from The Feinberg Graduate School for their achievements during their Ph.D), and approximately 39 MSc students (8 of whom received a recognition award for their excellence during their MSc). Her former Ph.D students include Jonathan Kipnis,

Jasmin Fisher Jasmin Fisher (born 1972) , is an Israeli-British biologist who is Professor of computational biology at University College London. She is Group Leader of the Fisher Lab at UCL Cancer Institute, which develops state-of-the-art computational mod ...

, and Asya Rolls.

References

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