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{{Infobox scientist
{{Infobox scientist
| honorific prefix =
| honorific prefix =
|image = Prof. Michal Schwarz.jpg
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| name = Michal Schwartz
| name = Michal Schwartz
| nationality = Israeli
| nationality = Israeli
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| birth_place = [[Tel Aviv]], Israel
| birth_place = [[Tel Aviv]], Israel
| workplaces = [[Weizmann Institute of Science]]
| workplaces = [[Weizmann Institute of Science]]
| known_for = [[protective autoimmunity]]
| fields = [[Neuroimmunology]]<ref name=gs/>
| doctoral_students = [[Jonathan Kipnis]]
| doctoral_students = {{Plainlist|
* [[Jonathan Kipnis]]{{fact}}
* [[Jasmin Fisher]]<ref name=fisher>{{Cite web |date=2013-02-24 |title=Making Sense of a Complex Situation - Weizmann Wonder Wander - News, Features and Discoveries |url=https://wis-wander.weizmann.ac.il/math-computer-sciencemade-institute/making-sense-complex-situation |access-date=2022-08-05 |website=weizmann.ac.il|publisher=Weizmann Wonder Wander - News, Features and Discoveries from the Weizmann Institute of Science |language=en}}</ref>
* [[Asya Rolls]]{{fact}}}}
| website = {{Official URL}}}}
'''Michal Schwartz''' (born 1 January 1950) is a professor of Neuroimmunology at the [[Weizmann Institute of Science]] and is internationally acclaimed as a path-breaking scientist in the study of [[immunology|Neuro-immunology]], introducing the dialogue between the immune system and the brain as 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]], Her immunotherapeutic approach to treat of harnessing the immune system to help brain to treat terminal neurodegenerative brain diseases such as [[Alzheimer's disease|Alzheimer Disease]] and [[Dementia]], is currently in expedite process of development.<ref name=epmc>{{EuropePMC}}</ref><ref name=gs/>


In her studies, she has shown, against prevailing wisdom at the time, that the immune system, supports a health 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 Disease and Dementia.
[[Asya Rolls]]
| website = {{URL|http://www.weizmann.ac.il/neurobiology/labs/schwartz/}}
https://www.weizmann.ac.il/brain-sciences/labs/schwartz/media
}}
[[File:Prof. Michal Schwarz.jpg|thumb|Prof. Michal Schwarz]]
'''Michal Schwartz''' (born 1 January 1950) is a professor of Neuroimmunology at the [[Weizmann Institute of Science]] 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 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,]] Her immunotherapeutic approach to treat of harnessing the immune system to help brain to treat terminal neurodegenerative brain diseases such as [[Alzheimer's disease|Alzheimer Disease]] and [[Dementia]], is currently in expedite process of development.


She discovered new roles for [[immune cells]] in repair and [[neurogenesis]], coining the term "[[Protective autoimmunity]]" and expanding the field of [[immunology]] in [[neuroscience]]. 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]], Biomedicine & Neuroscience category. {{As of|2022}} Her [[Google scholar]] Citation Index is 113.<ref name=gs>{{Google scholar id}}</ref>
In her pioneering studies, she has shown, against prevailing wisdom at the time, that the immune system, supports a health brain's function, and is vital for healing and protecting the brain in case of injury or disease. Prof. 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 Disease and Dementia.


== Education ==
She discovered new roles for [[immune cells]] in repair and [[neurogenesis]], coining the term "[[Protective autoimmunity]]" and expanding the field of [[immunology]] in [[neuroscience]]. 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]], Biomedicine & Neuroscience category. Goggle Citation Index 113.
Schwartz gained her Bachelor of Science (''with distinction'') in chemistry at [[Hebrew University of Jerusalem]] in 1972. She received her PhD in Immunology in 1977 at the [[Weizmann Institute of Science]], where she would later spend the majority of her career. She also spent time at the [[University of Michigan]], Ann Arbor, researching nerve regeneration.{{when}}


== Education and early career ==
== Career and research ==
Schwartz gained her Bachelor of Science (''with distinction'') in chemistry at [[Hebrew University of Jerusalem]] in 1972. She received her PhD in Immunology in 1977 at the [[Weizmann Institute of Science]], where she would later spend the majority of her career. She also spent time at the [[University of Michigan]], Ann Arbor, researching nerve regeneration. 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.<ref>{{cite web | url=https://www.britannica.com/biography/Michal-Schwartz | title=Michal Schwartz &#124; Britannica, Biography & Facts}}</ref>
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.<ref>{{cite web | url=https://www.britannica.com/biography/Michal-Schwartz | title=Michal Schwartz &#124; Britannica, Biography & Facts}}</ref>

== Detailed Description and Selected Publications ==
Schwartz's work in [[neuroimmunology]] has encompassed a wide range of pathologies in the [[central nervous system]] (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]] in health and disease. She coined the term "[[protective autoimmunity]]' and demonstrated the role of [[immune cells]] such as [[macrophages]] and [[T cells]] in [[spinal cord]] repair. She also identified specific brain areas for 'cross talk' between the CNS and the [[immune system]]. This cross talk is important for recruiting immune cells and maintaining a healthy brain, and her work outlines how disruption of this crosstalk can play a role in brain aging and [[neurodegenerative disease]]. She also showed this role in pregnancy and fetal [[brain development]], where immune disruption in the mother can be linked to [[neurodevelopmental disorders]] in children. Another focus of her work has been on repurposing cancer immunotherapies such as [[PD-1]] blockers to treat neurodegenerative disorders such as [[Alzheimer's disease]].
Schwartz's work in [[neuroimmunology]] has encompassed a wide range of pathologies in the [[central nervous system]] (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]] in health and disease. She coined the term "[[protective autoimmunity]]' and demonstrated the role of [[immune cells]] such as [[macrophages]] and [[T cells]] in [[spinal cord]] repair. She also identified specific brain areas for 'cross talk' between the CNS and the [[immune system]]. This cross talk is important for recruiting immune cells and maintaining a healthy brain, and her work outlines how disruption of this crosstalk can play a role in brain aging and [[neurodegenerative disease]]. She also showed this role in pregnancy and fetal [[brain development]], where immune disruption in the mother can be linked to [[neurodevelopmental disorders]] in children. Another focus of her work has been on repurposing cancer immunotherapies such as [[PD-1]] blockers to treat neurodegenerative disorders such as [[Alzheimer's disease]].


===Macrophages===

'''Bone Marrow-Derived Macrophages are Key Players in Central Nervous System Repair'''

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.
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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9662373
* 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.<ref> {{doi|10.1038/nm0798-814}}</ref>
* 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. http://dx.doi.org/10.1371/journal.pmed.1000113
* 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. <ref>{{doi|10.1371/journal.pmed.1000113}}</ref>
* 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. http://dx.doi.org/10.1016/j.immuni.2013.02.012
* 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. <ref>{{doi|10.1016/j.immuni.2013.02.012}}</ref>


'''Protective Autoimmunity in Brain Repair'''


===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 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.
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 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. http://dx.doi.org/10.1038/4734
* 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. <ref>{{doi|10.1038/4734}}</ref>
* 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. [http://www.ncbi.nlm.nih.gov/pubmed/11356861. http://www.ncbi.nlm.nih.gov/pubmed/11356861.]
* 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. <ref>{{doi|10.1523/JNEUROSCI.21-11-03740.2001}}</ref>
* 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. [http://dx.doi.org/10.1172/JCI12837. http://dx.doi.org/10.1172/JCI12837.]
* 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. <ref>{{doi|10.1172/JCI12837}}</ref>


===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 neurogenesis, 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. <ref>{{doi|10.1073/pnas.0402268101}}</ref>
'''Brain Homeostasis and Function are Dependent on the Functional Health of the Adaptive Immune-System'''
* 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. <ref>{{doi|10.1038/nn1629}}</ref>

* 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. <ref>{{doi|10.1126/science.1252945}}</ref>
Schwartz’s team was the world pioneer discovering 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 neurogenesis, 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. http://dx.doi.org/10.1073/pnas.0402268101
* 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. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16415867
* 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. http://dx.doi.org/10.1126/science.1252945
'''The Choroid Plexus as a Key Player in the Brain-Immune Axis'''


===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 brain led the Schwartz group to propose that 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 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 postmortem brains of infected patients who died from COVID-19.
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 brain led the Schwartz group to propose that 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 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 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 injured spinal cord is orchestrated by remote brain choroid plexus." ''Immunity'' 38, no. 3 (Mar 21 2013): 555-69. http://dx.doi.org/10.1016/j.immuni.2013.02.012
* 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 injured spinal cord is orchestrated by remote brain choroid plexus." ''Immunity'' 38, no. 3 (Mar 21 2013): 555-69. <ref>{{doi|10.1016/j.immuni.2013.02.012}}</ref>
* 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. <ref>{{doi|10.1093/brain/awt259}}</ref>

* 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. http://dx.doi.org/10.1093/brain/awt259
* 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. <ref>{{doi|10.1126/science.1252945}}</ref>
* 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. http://dx.doi.org/10.1126/science.1252945
* 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 ageing in an IFN-I-dependent manner." ''Nat Commun'' 8, no. 1 (Sep 28 2017): 717. <ref>{{doi|10.1038/s41467-017-00769-0}}</ref>
* 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 ageing in an IFN-I-dependent manner." ''Nat Commun'' 8, no. 1 (Sep 28 2017): 717. http://dx.doi.org/10.1038/s41467-017-00769-0


'''Immunotherapy for Alzheimer's Disease'''

The discoveries that adaptive immunity plays a key role in brain function and repair, and the need for bone marrow-derived macrophages to resolve local brain inflammation, together with the fact that AD and all forms of dementia are mainly age-related diseases, while the immune system is particularly affected by aging, led Schwartz to propose a new treatment for combating dementias. Schwartz suggested empowering systemic immunity, using a form of Immunotherapy by modestly blocking the inhibitory immune checkpoint PD1/PD-L1 pathway. This treatment drives an immune-dependent cascade of events, that allows 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. 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 an immunotherapy for AD are licensed to a small Biopharma company, Immnobrain Checkpoint. The company is about to initiate a clinical trial in AD patients, supported in part by the National Institute of Aging, and by The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership

* 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. http://dx.doi.org/10.1038/nm.4022
* Schwartz, M. "Can immunotherapy treat neurodegeneration?" ''Science'' 357, no. 6348 (Jul 21 2017): 254-55. [http://dx.doi.org/10.1126/science.aai8231\ http://dx.doi.org/10.1126/science.aai8231\]
* 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. http://dx.doi.org/10.1038/s41467-019-08352-5
* 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. http://dx.doi.org/10.1186/s13024-021-00458-z
* 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,''''' https://doi.org/10.1038/s43587-021-00149-w
* '''URL for complete list of publications (H factor 113, Google Scholar''': https://www.weizmann.ac.il/brain-sciences/labs/schwartz/publications

== Selected Awards ==

* 1999                    Alcon Research Awardee for Outstanding Contributions in vision research.
* 2002                    The Association for Research in Vision and Ophthalmology (ARVO) Award (Friedenwald Award) for outstanding research in the basic or clinical sciences in vision and ophthalmology.
* 2002 The G. Heiner Sell Memorial Lectureship for outstanding achievement in the field of spinal cord injury; the American Spinal Cord Injury Association (ASIA).
* 2002 International Glaucoma Review Award for daring, breakthrough, creative, original research in glaucoma

* 2008                    NARSAD (National Alliance for Research on Schizophrenia and Depression), Distinguished Investigator award
* 2009                    Shaked Prize, National award for outstanding brain research
* 2015                    The 2015 Blumberg Prize for excellence in medical science, Israel.
* 2016                    Accolade from the annual PROSE Awards for the book “NEUROIMMUNITY: How Brain Science Will Revolutionize the Way We Live and Age”, by Michal Schwartz with Anat London, Yale University Press (https://proseawards.com/winners/).

* 2016                    Profiled by Britannica Book of the Year (recognized among the scientists that advanced science and humanity), published since 1938 by Encyclopaedia Britannica<nowiki/>https://www.britannica.com/biography/Michal-Schwartz

* 2016-2018          President of the International Society of Neuroimmunology.
* 2017                   The Rappaport Prize for Excellence in the field of Biomedical Research
* 2019                   EMET Prize in biomedical research
* 2019                   Outstanding mentor of the year by the Israel Neuroscience society
* 2022                   FENS-EJN award given to her in recognition of her outstanding career in the area of Neuroimmunology.


===Immunotherapy ===
== Outstanding Recognition ==
The discoveries that adaptive immunity plays a key role in brain function and repair, and the need for bone marrow-derived macrophages to resolve local brain inflammation, together with the fact that AD and all forms of dementia are mainly age-related diseases, while the immune system is particularly affected by aging, led Schwartz to propose a new treatment for combating dementias. Schwartz suggested empowering systemic immunity, using a form of Immunotherapy by modestly blocking the inhibitory immune checkpoint PD1/PD-L1 pathway.{{fact}} This treatment drives an immune-dependent cascade of events, that allows 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. 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 an immunotherapy for AD are licensed to a small Biopharma company, Immnobrain Checkpoint. The company is about to initiate a clinical trial in AD patients, supported in part by the National Institute of Aging, and by The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership{{fact}}


* 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. <ref>{{doi|10.1038/nm.4022}}</ref>
* 2009                   Advanced ERC award, “Can immune system, rejuvenation restore age-related memory loss?”
* Schwartz, M. "Can immunotherapy treat neurodegeneration?" ''Science'' 357, no. 6348 (Jul 21 2017): 254-55. <ref>{{doi|10.1126/science.aai8231}}</ref>
* 2017                   Advanced European Research Council grant (Advanced ERC award), “Immune checkpoint blockade for fighting Alzheimer’s disease –Immune CheckpointsAD."
* 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. <ref>{{doi|10.1038/s41467-019-08352-5}}</ref>
* 2020                   Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership
* 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. <ref>{{doi|10.1186/s13024-021-00458-z}}</ref>
* 2021 Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from National Institute of Health
* 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, <ref>{{doi|10.1038/s43587-021-00149-w}}</ref>


== Women Career Awards ==
=== Selected Awards ===
* 1999: Alcon Research Awardee for Outstanding Contributions in vision research{{fact}}
* 2002: The Association for Research in Vision and Ophthalmology (ARVO) Award (Friedenwald Award) for outstanding research in the basic or clinical sciences in vision and ophthalmology{{fact}}
* 2002: The G. Heiner Sell Memorial Lectureship for outstanding achievement in the field of spinal cord injury{{fact}}
* 2002: International Glaucoma Review Award for daring, breakthrough, creative, original research in glaucoma{{fact}}
* 2008: NARSAD (National Alliance for Research on Schizophrenia and Depression), Distinguished Investigator award{{fact}}
* 2009: Shaked Prize, National award for outstanding brain research{{fact}}
* 2015: The 2015 Blumberg Prize for excellence in medical science, Israel{{fact}}
* 2016: Accolade from the annual PROSE Awards for the book “NEUROIMMUNITY: How Brain Science Will Revolutionize the Way We Live and Age”,{{fact}}
* 2016: Profiled by Britannica Book of the Year<ref>published since 1938 by Encyclopaedia Britannica https://www.britannica.com/biography/Michal-Schwartz</ref>
* 2016-2018: President of the International Society of Neuroimmunology{{fact}}
* 2017: The Rappaport Prize for Excellence in the field of Biomedical Research{{fact}}
* 2019: EMET Prize in biomedical research{{fact}}
* 2019: Outstanding mentor of the year by the Israel Neuroscience society{{fact}}
* 2022: FENS-EJN award given to her in recognition of her outstanding career in the area of Neuroimmunology{{fact}}


=== Outstanding Recognition ===
* 2000                    Career Woman of the Year 2000, Israel.
* 2006                     Jewish Woman's Magazine award, “10 women to watch in 5767”. Advanced European
* 2017                     Selected as the most influential woman of the year 2017 by Lady Globes


* 2009: Advanced ERC award, “Can immune system, rejuvenation restore age-related memory loss?” {{fact}}
== Honorary Doctorate ==
* 2017: Advanced European Research Council grant (Advanced ERC award), “Immune checkpoint blockade for fighting Alzheimer’s disease –Immune CheckpointsAD."
* 2020: Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership{{fact}}
* 2021: Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from National Institute of Health
=== Women Career Awards ===


* 2000: Career Woman of the Year 2000, Israel{{fact}}
* 2008                   Honorary doctorate, Ben-Gurion University, Israel
* 2006: Jewish Woman's Magazine award, “10 women to watch in 5767”. Advanced European{{fact}}
* 2018                   Honorary doctorate, The Interdisciplinary Center, Herzliya, Israel
* 2017: Selected as the most influential woman of the year 2017 by Lady Globes{{fact}}


== Selected Honorary Lectures ==
=== Honorary Doctorates ===


* 2008: Honorary doctorate, Ben-Gurion University, Israel{{fact}}
* 1999                    Award lecture, Alcon Research Institute Symposium (Alcon Awardee for Outstanding Contributions in the Field of Vision Research), Texas, USA,
* 2018: Honorary doctorate, The Interdisciplinary Center, Herzliya, Israel{{fact}}
* 2001                     Named Honorary Lecturer The 22nd Annual Peter and Eva Safar Annual Lectureship in Medical Science and humanities, University of Pittsburgh, USA
* 2002                     Named lecture, distinguished lectureship, The G. Heiner Sell Memorial Lectureship in the Joint meeting of the American Spinal Injury Association and the International Medical Society of


=== Selected Honorary Lectures ===
Paraplegia, Vancouver, Canada.


* 2002                     Award lecture, Association for Research in Vision and Ophthalmology (Lecturer as Recipient of the Friedenwald Award), Fort Lauderdale, Florida, USA
* 1999: Award lecture, Alcon Research Institute Symposium (Alcon Awardee for Outstanding Contributions in the Field of Vision Research), Texas, USA{{fact}}
* 2001: Named Honorary Lecturer The 22nd Annual Peter and Eva Safar Annual Lectureship in Medical Science and humanities, University of Pittsburgh, USA{{fact}}
* 2003                     Presidential lecture, European Neurological Society Meeting, Istanbul, Turkey,
* 2002: Named lecture, distinguished lectureship, The G. Heiner Sell Memorial Lectureship in the Joint meeting of the American Spinal Injury Association and the International Medical Society of Paraplegia, Vancouver, Canada{{fact}}
* 2009                     Presidential Lecture, at the Annual Meeting of the Psychoneuroimmunology Research Society, Breckenridge Colorado, USA
* 2002: Award lecture, Association for Research in Vision and Ophthalmology (Lecturer as Recipient of the Friedenwald Award), Fort Lauderdale, Florida, USA
* 2012                     Presidential Lecture, Canadian Association of Neuropathologists, Mont Tremblant, Quebec, Canada
* 2003: Presidential lecture, European Neurological Society Meeting, Istanbul, Turkey,{{fact}}
* 2015                     Named lecture, The Gabriele M. Zu Rhein Lectureship, University of Wisconsin-Madison, USA
* 2009: Presidential Lecture, at the Annual Meeting of the Psychoneuroimmunology Research Society, Breckenridge Colorado, USA{{fact}}
* 2016                     Named lecture, Rita Levi Moltanchini, Keynote lecture, International Society of Neuroimmunology meeting, Jerusalem, Israel
* 2012: Presidential Lecture, Canadian Association of Neuropathologists, Mont Tremblant, Quebec, Canada{{fact}}
* 2017                     Named lecture, WALS lecture, NIH (the highest-profile lecture program at the NIH. Each season includes among the biggest names in biomedical and behavioral research), Maryland, USA
* 2015: Named lecture, The Gabriele M. Zu Rhein Lectureship, University of Wisconsin-Madison, USA{{fact}}
* 2018                     Keynote lecture, AAIC Alzheimer‘s Association International Conference, Chicago USA,
* 2016: Named lecture, Rita Levi Moltanchini, Keynote lecture, International Society of Neuroimmunology meeting, Jerusalem, Israel{{fact}}
* 2022                     FENS-EJN Award Lecture at FENS Forum 2022, Paris, France
* 2017: Named lecture, WALS lecture, NIH (the highest-profile lecture program at the NIH. Each season includes among the biggest names in biomedical and behavioral research), Maryland, USA{{fact}}
* 2018: Keynote lecture, AAIC Alzheimer‘s Association International Conference, Chicago USA{{fact}}
* 2022: FENS-EJN Award Lecture at FENS Forum 2022, Paris, France{{fact}}


== Mentorships ==
=== Students ===


Prof. Schwartz has mentored approximately 40 PhD students (12 of whom received recognition awards by The Feinberg Graduate School for their achievements during their PhD), and approximately 39 MSc students (8 of whom received a recognition award for their excellence during their MSc).
Schwartz has mentored approximately 40 PhD students{{fact}} (12 of whom received recognition awards by The Feinberg Graduate School for their achievements during their PhD), and approximately 39 MSc students (8 of whom received a recognition award for their excellence during their MSc).{{fact}} Her former PhD students include [[Jonathan Kipnis]]{{fact}}, [[Jasmin Fisher]]<ref name=fisher/> and [[Asya Rolls]].{{fact}}


== References ==
== References ==

Revision as of 21:11, 9 August 2022

Michal Schwartz
Born (1950-01-01) 1 January 1950 (age 74)
Tel Aviv, Israel
NationalityIsraeli
Scientific career
FieldsNeuroimmunology[1]
InstitutionsWeizmann Institute of Science
Doctoral students
Websitewww.weizmann.ac.il/neurobiology/labs/schwartz Edit this at Wikidata

Michal Schwartz (born 1 January 1950) is a professor of Neuroimmunology at the Weizmann Institute of Science 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 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, Her immunotherapeutic approach to treat of harnessing the immune system to help brain to treat terminal neurodegenerative brain diseases such as Alzheimer Disease and Dementia, is currently in expedite process of development.[3][1]

In her studies, she has shown, against prevailing wisdom at the time, that the immune system, supports a health 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 Disease and Dementia.

She discovered new roles for immune cells in repair and neurogenesis, coining the term "Protective autoimmunity" and expanding the field of immunology in neuroscience. 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, Biomedicine & Neuroscience category. As of 2022 Her Google scholar Citation Index is 113.[1]

Education

Schwartz gained her Bachelor of Science (with distinction) in chemistry at Hebrew University of Jerusalem in 1972. She received her PhD in Immunology in 1977 at the Weizmann Institute of Science, where she would later spend the majority of her career. She also spent time at the University of Michigan, Ann Arbor, researching nerve regeneration.[when?]

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.[4] Schwartz's work in neuroimmunology has encompassed a wide range of pathologies in the central nervous system (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 in health and disease. She coined the term "protective autoimmunity' and demonstrated the role of immune cells such as macrophages and T cells in spinal cord repair. She also identified specific brain areas for 'cross talk' between the CNS and the immune system. This cross talk is important for recruiting immune cells and maintaining a healthy brain, and her work outlines how disruption of this crosstalk can play a role in brain aging and neurodegenerative disease. She also showed this role in pregnancy and fetal brain development, where immune disruption in the mother can be linked to neurodevelopmental disorders in children. Another focus of her work has been on repurposing cancer immunotherapies such as PD-1 blockers to treat neurodegenerative disorders such as Alzheimer's disease.

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.[5]
  • 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. [6]
  • 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. [7]

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 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. [8]
  • 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. [9]
  • 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. [10]

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 neurogenesis, 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. [11]
  • 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. [12]
  • 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. [13]

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 brain led the Schwartz group to propose that 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 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 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 injured spinal cord is orchestrated by remote brain choroid plexus." Immunity 38, no. 3 (Mar 21 2013): 555-69. [14]
  • 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. [15]
  • 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. [16]
  • 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 ageing in an IFN-I-dependent manner." Nat Commun 8, no. 1 (Sep 28 2017): 717. [17]

Immunotherapy

The discoveries that adaptive immunity plays a key role in brain function and repair, and the need for bone marrow-derived macrophages to resolve local brain inflammation, together with the fact that AD and all forms of dementia are mainly age-related diseases, while the immune system is particularly affected by aging, led Schwartz to propose a new treatment for combating dementias. Schwartz suggested empowering systemic immunity, using a form of Immunotherapy by modestly blocking the inhibitory immune checkpoint PD1/PD-L1 pathway.[citation needed] This treatment drives an immune-dependent cascade of events, that allows 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. 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 an immunotherapy for AD are licensed to a small Biopharma company, Immnobrain Checkpoint. The company is about to initiate a clinical trial in AD patients, supported in part by the National Institute of Aging, and by The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership[citation needed]

  • 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. [18]
  • Schwartz, M. "Can immunotherapy treat neurodegeneration?" Science 357, no. 6348 (Jul 21 2017): 254-55. [19]
  • 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. [20]
  • 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. [21]
  • 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, [22]

Selected Awards

  • 1999: Alcon Research Awardee for Outstanding Contributions in vision research[citation needed]
  • 2002: The Association for Research in Vision and Ophthalmology (ARVO) Award (Friedenwald Award) for outstanding research in the basic or clinical sciences in vision and ophthalmology[citation needed]
  • 2002: The G. Heiner Sell Memorial Lectureship for outstanding achievement in the field of spinal cord injury[citation needed]
  • 2002: International Glaucoma Review Award for daring, breakthrough, creative, original research in glaucoma[citation needed]
  • 2008: NARSAD (National Alliance for Research on Schizophrenia and Depression), Distinguished Investigator award[citation needed]
  • 2009: Shaked Prize, National award for outstanding brain research[citation needed]
  • 2015: The 2015 Blumberg Prize for excellence in medical science, Israel[citation needed]
  • 2016: Accolade from the annual PROSE Awards for the book “NEUROIMMUNITY: How Brain Science Will Revolutionize the Way We Live and Age”,[citation needed]
  • 2016: Profiled by Britannica Book of the Year[23]
  • 2016-2018: President of the International Society of Neuroimmunology[citation needed]
  • 2017: The Rappaport Prize for Excellence in the field of Biomedical Research[citation needed]
  • 2019: EMET Prize in biomedical research[citation needed]
  • 2019: Outstanding mentor of the year by the Israel Neuroscience society[citation needed]
  • 2022: FENS-EJN award given to her in recognition of her outstanding career in the area of Neuroimmunology[citation needed]

Outstanding Recognition

  • 2009: Advanced ERC award, “Can immune system, rejuvenation restore age-related memory loss?” [citation needed]
  • 2017: Advanced European Research Council grant (Advanced ERC award), “Immune checkpoint blockade for fighting Alzheimer’s disease –Immune CheckpointsAD."
  • 2020: Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from The Alzheimer's Association 'Part the Cloud' + Bill Gates Partnership[citation needed]
  • 2021: Her Alzheimer’s disease therapy, currently under expedited development, received an award for clinical translation from National Institute of Health

Women Career Awards

  • 2000: Career Woman of the Year 2000, Israel[citation needed]
  • 2006: Jewish Woman's Magazine award, “10 women to watch in 5767”. Advanced European[citation needed]
  • 2017: Selected as the most influential woman of the year 2017 by Lady Globes[citation needed]

Honorary Doctorates

  • 2008: Honorary doctorate, Ben-Gurion University, Israel[citation needed]
  • 2018: Honorary doctorate, The Interdisciplinary Center, Herzliya, Israel[citation needed]

Selected Honorary Lectures

  • 1999: Award lecture, Alcon Research Institute Symposium (Alcon Awardee for Outstanding Contributions in the Field of Vision Research), Texas, USA[citation needed]
  • 2001: Named Honorary Lecturer The 22nd Annual Peter and Eva Safar Annual Lectureship in Medical Science and humanities, University of Pittsburgh, USA[citation needed]
  • 2002: Named lecture, distinguished lectureship, The G. Heiner Sell Memorial Lectureship in the Joint meeting of the American Spinal Injury Association and the International Medical Society of Paraplegia, Vancouver, Canada[citation needed]
  • 2002: Award lecture, Association for Research in Vision and Ophthalmology (Lecturer as Recipient of the Friedenwald Award), Fort Lauderdale, Florida, USA
  • 2003: Presidential lecture, European Neurological Society Meeting, Istanbul, Turkey,[citation needed]
  • 2009: Presidential Lecture, at the Annual Meeting of the Psychoneuroimmunology Research Society, Breckenridge Colorado, USA[citation needed]
  • 2012: Presidential Lecture, Canadian Association of Neuropathologists, Mont Tremblant, Quebec, Canada[citation needed]
  • 2015: Named lecture, The Gabriele M. Zu Rhein Lectureship, University of Wisconsin-Madison, USA[citation needed]
  • 2016: Named lecture, Rita Levi Moltanchini, Keynote lecture, International Society of Neuroimmunology meeting, Jerusalem, Israel[citation needed]
  • 2017: Named lecture, WALS lecture, NIH (the highest-profile lecture program at the NIH. Each season includes among the biggest names in biomedical and behavioral research), Maryland, USA[citation needed]
  • 2018: Keynote lecture, AAIC Alzheimer‘s Association International Conference, Chicago USA[citation needed]
  • 2022: FENS-EJN Award Lecture at FENS Forum 2022, Paris, France[citation needed]

Students

Schwartz has mentored approximately 40 PhD students[citation needed] (12 of whom received recognition awards by The Feinberg Graduate School for their achievements during their PhD), and approximately 39 MSc students (8 of whom received a recognition award for their excellence during their MSc).[citation needed] Her former PhD students include Jonathan Kipnis[citation needed], Jasmin Fisher[2] and Asya Rolls.[citation needed]

References

  1. ^ a b c Michal Schwartz publications indexed by Google Scholar Edit this at Wikidata
  2. ^ a b "Making Sense of a Complex Situation - Weizmann Wonder Wander - News, Features and Discoveries". weizmann.ac.il. Weizmann Wonder Wander - News, Features and Discoveries from the Weizmann Institute of Science. 2013-02-24. Retrieved 2022-08-05.
  3. ^ Michal Schwartz publications from Europe PubMed Central
  4. ^ "Michal Schwartz | Britannica, Biography & Facts".
  5. ^ doi:10.1038/nm0798-814
  6. ^ doi:10.1371/journal.pmed.1000113
  7. ^ doi:10.1016/j.immuni.2013.02.012
  8. ^ doi:10.1038/4734
  9. ^ doi:10.1523/JNEUROSCI.21-11-03740.2001
  10. ^ doi:10.1172/JCI12837
  11. ^ doi:10.1073/pnas.0402268101
  12. ^ doi:10.1038/nn1629
  13. ^ doi:10.1126/science.1252945
  14. ^ doi:10.1016/j.immuni.2013.02.012
  15. ^ doi:10.1093/brain/awt259
  16. ^ doi:10.1126/science.1252945
  17. ^ doi:10.1038/s41467-017-00769-0
  18. ^ doi:10.1038/nm.4022
  19. ^ doi:10.1126/science.aai8231
  20. ^ doi:10.1038/s41467-019-08352-5
  21. ^ doi:10.1186/s13024-021-00458-z
  22. ^ doi:10.1038/s43587-021-00149-w
  23. ^ published since 1938 by Encyclopaedia Britannica https://www.britannica.com/biography/Michal-Schwartz
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