Robyn S. Klein

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Robyn Klein
RSK photo crop copy.jpg
NationalityAmerican
Alma materBarnard College, Albert Einstein College of Medicine, Brigham and Women's Hospital, Massachusetts General Hospital
Known forVirus mediated cognitive impairment, sex-differences in Multiple Sclerosis
AwardsDana Foundation Award for Neuroimmunology Distinguished Educator Award, Washington University
Scientific career
FieldsNeuroimmunology
InstitutionsWashington University in St. Louis, Missouri

Robyn S. Klein is an American neuroimmunologist as well as the Vice Provost and Associate Dean for Graduate Education at Washington University in St. Louis Missouri. Klein is also a professor in the Departments of Medicine, Anatomy & Neurobiology, and Pathology & Immunology. Her research explores the pathogenesis of neuroinflammation in the central nervous system by probing how immune signalling molecules regulate blood brain barrier permeability. Klein is also a fervent advocate for gender equity in STEM, publishing mechanisms to improve gender equity in speakers at conferences, participating nationally on gender equity discussion panels, and through service as the president of the Academic Women’s Network at the Washington University School of Medicine.

Contents

Early life and education

Klein pursued her undergraduate studies at Columbia University’s Barnard College in New York City. [1] In 1985, Klein completed her Bachelors of Arts in Biological Sciences, graduating with honors. [2] After her undergraduate degree, Klein pursued an MD-PhD at Albert Einstein College of Medicine. [2] On her way to obtaining her dual-degree, Klein completed a Masters in Neuroscience in 1990 at Albert Einstein College and then graduated in 1993 with a Ph.D. in Neuroscience and an M.D. from Albert Einstein. [1] Klein then completed her internship and her residency in medicine at the Brigham and Women’s Hospital and subspecialty training in Infectious Diseases at Massachusetts General Hospital, both in Boston, Massachusetts. [3] Throughout her experiences in the clinic, Klein became interested in the neuroprotective role of brain immune responses, as many Acquired Immunodeficiency Syndrome (AIDS) patients presented with severe brain infections in their immune compromised state. She wondered how the interplay of brain infection and immune responses impacted on overall brain function in acute and chronic states.

Following these clinical experiences and inspirations, Klein completed postdoctoral training in Immunology at Harvard Medical School. [4] In 1999, Klein was the first to demonstrate that the HIV envelope protein could induce calcium transients in neurons and astrocytes via chemokine receptor activation. [5] Her first author paper in the Journal of Immunology highlighting these findings provided a basis for understanding the neuronal damage and inflammation that result from HIV-1 encephalitis. [5]

In 2002, Klein helped discover that deficiency in Chemokine Receptor 2 (CCR2) decreased monocyte recruitment to the CNS which help reduce the symptoms of experimental autoimmune encephalitis. [6] In Klein’s first author paper in development in 2001, she reported that the chemokine CXC12 and its receptor CXCR4 are important in cerebellar granule cell proliferation and migration. [7] Klein’s work has continually shown that immune signalling in the brain contributes to brain disease pathogenesis and cognitive defects that could be treated with immune targeting therapies.

Career and research

After Klein completed her postdoctoral work, she was recruited to Washington University School of Medicine in St. Louis, Missouri in 2003. [2] At WUSM, Klein was appointed, and still holds, professorships in the Departments of Medicine, Pathology & Immunology, and Neuroscience. [2] After Klein arrived at WUSM, she founded the Center for Neuroimmunology and Neuroinfectious Diseases and now directs the center. [2] In order to train the next leaders in neuroimmunology, Klein also developed a neuroimmunology basic and translational science research program where scientists work to probe the neuroimmune mechanisms underlying the pathogenesis of brain related diseases. [2] In 2017, Klein was named the Vice Provost and Assistant Dean for Graduate Education for the Division of Biology and Biomedical Sciences. [8] In addition to promoting departmental collaborations and ensuring that graduate students are supported in their pursuits of a variety of different career paths, Klein is focusing on improving diversity and equity in the program by recruiting students from underrepresented groups. [8] These goals are in line with Klein's past achievements and involvements in advocating for diversity and equity in science. [8] She is the co-director of the Amgen Scholars Program at Washington University ensuring that a diverse group of undergraduate students have the opportunity to experience science in top labs. [9] Further, as the president of the Academic Women’s Network at the Washington University School of Medicine, Klein promotes career development and mentorship for women in science. [10] Klein has conducted research on gender bias in conference organization, highlighting the fact that conference committee composition matters in the selection of diverse speakers. [11] Klein reports that “naming the problem is the first step in solving it”, suggesting that conducting quantitative studies on gender bias in scientific meetings, hiring, acceptances, grant awards etc. will be the first step towards actually solving these issues and increasing representation in science. [11]

Research in the Klein Lab is focused on exploring the cellular and molecular mechanisms that orchestrate inflammation and mediate its effect on the central nervous system. [12] Her lab looks specifically at inflammation as a result of viral and autoimmune encephalitides via the interactions between endothelial, neural, and immune cell interactions. Her lab has focused on two main mechanisms with which the immune system signals to and interacts with the central nervous system: the first is through leukocytes infiltrating the brain and the second is through cytokines and chemokines directly affecting neuronal function. [12] Her lab has extensively explored how cytokines and chemokines affect blood brain barrier permeability and her lab has discovered a novel role for cytokines and chemokines in the regulation of blood-brain barrier permeability to arboviruses, and protective versus pathogenic leukocytes. [12] For example, since West Nile Virus has been shown to cause significant brain damage leading to memory loss, Klein’s lab researches ways to prevent this from occurring. [13] She found that microglia, the brain’s innate immune cells,  accumulate around neurons at the site of infection and complement protein is also highly expressed at the site of infection. [14] Klein also found that these microglia remain active long after infection clears leading to post-infection inflammation and further synapse loss. [13] These findings signify increased neuronal pruning and destruction by microglia leading to memory loss in patients with West Nile Virus infections. [14]

Since inflammatory cues during infection regulate central nervous system repair via the regulation of neural stem cells, this is yet another mechanism that the Klein Lab probes to understand how viral infections and demyelinating diseases cause impaired learning and memory. Her lab specifically explores the cues that drive the localization, proliferation, and differentiation of neural stem cells to mediate their ability to successfully repair damaged neurons and myelin. [15] [16] Since demyelinating diseases are a focus of the lab, Klein made a discovery in 2014, that multiple sclerosis (MS) disproportionally effects women compared to men due to higher expression of a blood vessel receptor protein S1PR2. [17] Further, this protein was expressed at even higher levels in MS patients in brain regions more affected by MS. [17] Another goal of the Klein lab is to understand how glial cells regulate T cell activity in viral infections and autoimmune inflammation in the brain. [18] Her research in these areas has highlighted the extensive communication between astrocytes and T cells such that astrocytes play a critical role in trafficking T cells throughout the CNS during disease. Overall Klein's work contributes to an increased understanding of normal central nervous system surveillance and its relationship to inflammatory patterns that are observed in disease states which ultimately helps to identify therapeutic targets for the wide array of brain diseases that lack cures and treatments.

Memberships

Awards and honors

Publications

Related Research Articles

<span class="mw-page-title-main">Stromal cell-derived factor 1</span> Mammalian protein found in Homo sapiens

The stromal cell-derived factor 1 (SDF-1), also known as C-X-C motif chemokine 12 (CXCL12), is a chemokine protein that in humans is encoded by the CXCL12 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types. Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group. CXCL12 signaling has been observed in several cancers. The CXCL12 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">Chemokine</span> Small cytokines or signaling proteins secreted by cells

Chemokines, or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addition to playing a major role in the activation of host immune responses, chemokines are important for biological processes, including morphogenesis and wound healing, as well as in the pathogenesis of diseases like cancers.

<span class="mw-page-title-main">Japanese encephalitis</span> Infection of the brain caused by the Japanese encephalitis virus

Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include headache, vomiting, fever, confusion and seizures. This occurs about 5 to 15 days after infection.

<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

<span class="mw-page-title-main">CCL2</span> Mammalian protein found in Homo sapiens

The chemokine ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 tightly regulates cellular mechanics and thereby recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.

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, homeostasis, and response to injuries. A long-term goal of this rapidly developing research area is to further develop our understanding of the pathology of certain neurological diseases, some of which have no clear etiology. In doing so, neuroimmunology contributes to development of new pharmacological treatments for several neurological conditions. Many types of interactions involve both the nervous and immune systems including the physiological functioning of the two systems in health and disease, malfunction of either and or both systems that leads to disorders, and the physical, chemical, and environmental stressors that affect the two systems on a daily basis.

<span class="mw-page-title-main">Neuroimmune system</span>

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers, mediating neuroinflammation and wound healing in damaged neurons, and mobilizing host defenses against pathogens.

Chemokine ligand 1 (CCL1) is also known as small inducible cytokine A1 and I-309 in humans. CCL1 is a small glycoprotein that belongs to the CC chemokine family.

Neurovirology is an interdisciplinary field which represents a melding of clinical neuroscience, virology, immunology, and molecular biology. The main focus of the field is to study viruses capable of infecting the nervous system. In addition to this, the field studies the use of viruses to trace neuroanatomical pathways, for gene therapy, and to eliminate detrimental populations of neural cells.

Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury, toxic metabolites, or autoimmunity. In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues. The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood–brain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells. However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response. Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood–brain barrier may occur.

<span class="mw-page-title-main">Jonathan Kipnis</span> Neuroscientist

Jonathan Kipnis is a neuroscientist, immunologist, and professor of pathology and immunology at the Washington University School of Medicine. His lab studies interactions between the immune system and nervous system. He is best known for his lab's discovery of meningeal lymphatic vessels in humans and mice, which has impacted research on neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis, neuropsychiatric disorders, such as anxiety, and neurodevelopmental disorders such as autism and Rett syndrome.

Microglia are the primary immune cells of the central nervous system, similar to peripheral macrophages. They respond to pathogens and injury by changing morphology and migrating to the site of infection/injury, where they destroy pathogens and remove damaged cells.

Anirban Basu is an Indian neurobiologist, who is primarily interested in neurovirology, a senior scientist at the National Brain Research Centre, a deemed to be university, located in Manesar, Gurgaon, Haryana. He is internationally known for his studies on Japanese encephalitis. Basu is an elected fellow of all the three major Indian science Academies namely the Indian Academy of Sciences, the Indian National Science Academy and the National Academy of Sciences, India as well as of the West Bengal Academy of Science and Technology. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the prominent Indian science awards, for his contributions to biosciences and biotechnology, in 2010.

Carol Shoshkes Reiss, an American viral immunologist, has been professor in New York University's department of biology since 1991. Her research focused on the dynamic contest between the mouse immune system and virus replication during infection of the central nervous system. Reiss was editor-in-chief of the journal Viral Immunology (2000–2006) and is currently editor-in-chief of the journal DNA and Cell Biology (2012–present).

<span class="mw-page-title-main">Katerina Akassoglou</span> Greek neuroimmunologist

Katerina Akassoglou is a neuroimmunologist who is a Senior Investigator and Director of In Vivo Imaging Research at the Gladstone Institutes. Akassoglou holds faculty positions as a Professor of Neurology at the University of California, San Francisco. Akassoglou has pioneered investigations of blood-brain barrier integrity and development of neurological diseases. She found that compromised blood-brain barrier integrity leads to fibrinogen leakage into the brain inducing neurodegeneration. Akassoglou is internationally recognized for her scientific discoveries.

Helga (Elga) De Vries is a Dutch neuroimmunologist and a Full Professor in the Department of Molecular Cell Biology and Immunology at Amsterdam University Medical Centers in Amsterdam, The Netherlands. De Vries is a leader in the field of blood brain barrier research. She founded the Dutch Blood Brain Barrier Network and is the President of the International Brain Barrier Society. De Vries’ research explores the interactions between the brain and the immune system and she specifically looks at neurovascular biology in the context of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease.

<span class="mw-page-title-main">Marion Buckwalter</span> American neurologist

Marion Buckwalter is an American neurologist and neuroscientist and Professor of Neurology and Neurosurgery at the Stanford University School of Medicine. Buckwalter studies how inflammatory responses affect brain recovery after injury or insult, with a specific emphasis on the neuroimmune and glial cell response after stroke.

Anne Cross is an American neurologist and neuroimmunologist and the Section Head of Neuroimmunology at Washington University School of Medicine in St. Louis, Missouri. Cross holds the Manny and Rosalyn Rosenthal–Dr. John L. Trotter Endowed Chair in Neuroimmunology at WUSTL School of Medicine and co-directs the John L Trotter Multiple Sclerosis Clinic at Barnes-Jewish Hospital. Cross is a leader in the field of neuroimmunology and was the first to discover the role of B cells in the pathogenesis of multiple sclerosis in animals and then in humans. Cross now develops novel imaging techniques to observe inflammation and demyelination in the central nervous systems of MS patients for diagnosis and disease management.

<span class="mw-page-title-main">Francisco J. Quintana</span>

Francisco J. Quintana is an Argentinean-American immunologist and neuroscientist, and Professor of Neurology at Harvard Medical School. His lab studies interactions between the immune system and nervous system. He is best known for his work on the regulation of inflammation by astrocytes, and by the study of the role of the Aryl Hydrocarbon Receptor in the regulation of the immune response by pollutants, the microbial flora and metabolism. Dr. Quintana's research has implications for our understanding of the pathology of multiple inflammatory disorders including multiple sclerosis, Type 1 diabetes and Inflammatory Bowel Disease, and also brain tumors and infectious diseases. His work has also led to the development of novel therapeutic interventions, and novel techniques for the investigation of regulatory mechanisms involved in the control of inflammation, including RABID-seq, FIND-seq and SPEAC-seq.

<span class="mw-page-title-main">Burkhard Becher</span> German immunologist, biomedical researcher

Burkhard Becher is a German immunologist, biomedical researcher and academic. He is a Professor and Chair of the Institute of Experimental Immunology at the University of Zurich.

References

  1. 1 2 "Robyn S. Klein, MD, PhD". Infectious Diseases. Retrieved 2020-04-02.
  2. 1 2 3 4 5 6 "Organizer: Cell Symposia Neuro-Immune Axis: Reciprocal Regulation in Development, Health, and Disease". www.cell-symposia.com. Retrieved 2020-04-02.
  3. "Klein, Robyn" (in Italian). Retrieved 2020-04-02.
  4. "Klein, Robyn" (in Italian). Retrieved 2020-04-04.
  5. 1 2 Klein, R. S.; Williams, K. C.; Alvarez-Hernandez, X.; Westmoreland, S.; Force, T.; Lackner, A. A.; Luster, A. D. (1999-08-01). "Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS". Journal of Immunology. 163 (3): 1636–1646. doi: 10.4049/jimmunol.163.3.1636 . ISSN   0022-1767. PMID   10415069. S2CID   23749985.
  6. Izikson, Leonid; Klein, Robyn S.; Charo, Israel F.; Weiner, Howard L.; Luster, Andrew D. (2000-10-02). "Resistance to Experimental Autoimmune Encephalomyelitis in Mice Lacking the Cc Chemokine Receptor (Ccr2)". The Journal of Experimental Medicine. 192 (7): 1075–1080. doi:10.1084/jem.192.7.1075. ISSN   0022-1007. PMC   2193310 . PMID   11015448.
  7. Klein, R. S.; Rubin, J. B.; Gibson, H. D.; DeHaan, E. N.; Alvarez-Hernandez, X.; Segal, R. A.; Luster, A. D. (June 2001). "SDF-1 alpha induces chemotaxis and enhances Sonic hedgehog-induced proliferation of cerebellar granule cells". Development. 128 (11): 1971–1981. doi:10.1242/dev.128.11.1971. ISSN   0950-1991. PMID   11493520.
  8. 1 2 3 4 5 6 7 8 9 10 "Klein named vice provost and associate dean for graduate education". Washington University School of Medicine in St. Louis. 2017-07-20. Retrieved 2020-04-02.
  9. "University receives new grant to fund Amgen Scholars Program". Washington University School of Medicine in St. Louis. 2018-12-07. Retrieved 2020-04-02.
  10. "Robyn S. Klein". Diversity & Inclusion. 20 July 2017. Retrieved 2020-04-02.
  11. 1 2 "Study: Accomplished female scientists often overlooked". Washington University School of Medicine in St. Louis. 2017-04-20. Retrieved 2020-04-02.
  12. 1 2 3 "Robyn Klein, MD, PhD". The Hope Center. 22 October 2019. Retrieved 2020-04-02.
  13. 1 2 "Memory loss caused by West Nile virus explained | The Source | Washington University in St. Louis". The Source. 2016-06-22. Retrieved 2020-04-02.
  14. 1 2 Vasek, Michael J.; Garber, Charise; Dorsey, Denise; Durrant, Douglas M.; Bollman, Bryan; Soung, Allison; Yu, Jinsheng; Perez-Torres, Carlos; Frouin, Arnaud; Wilton, Daniel K.; Funk, Kristen (June 2016). "A complement–microglial axis drives synapse loss during virus-induced memory impairment". Nature. 534 (7608): 538–543. Bibcode:2016Natur.534..538V. doi:10.1038/nature18283. ISSN   1476-4687. PMC   5452615 . PMID   27337340.
  15. Garber, Charise; Vasek, Michael J.; Vollmer, Lauren L.; Sun, Tony; Jiang, Xiaoping; Klein, Robyn S. (February 2018). "Astrocytes decrease adult neurogenesis during virus-induced memory dysfunction via IL-1". Nature Immunology. 19 (2): 151–161. doi:10.1038/s41590-017-0021-y. ISSN   1529-2916. PMC   5786497 . PMID   29292385.
  16. "Home | Robyn Klein Lab | Washington University in St. Louis". kleinlab.wustl.edu. Retrieved 2020-04-04.
  17. 1 2 "Study helps explain why MS is more common in women | The Source | Washington University in St. Louis". The Source. 2014-05-08. Retrieved 2020-04-02.
  18. "Research | Robyn Klein Lab | Washington University in St. Louis". kleinlab.wustl.edu. Retrieved 2020-04-02.
  19. "2020 Distinguished Faculty Awards announced". Washington University School of Medicine in St. Louis. 2020-03-05. Retrieved 2020-04-02.
  20. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 "Publications | Robyn Klein Lab | Washington University in St. Louis". kleinlab.wustl.edu. Retrieved 2020-04-02.