Beth Stevens
Born1970 (age 5354)
NationalityAmerican
Alma mater
Known forMicroglia and complement receptor-based synaptic pruning mechanisms
SpouseRob Graham
Scientific career
Fields
InstitutionsBoston Children's Hospital
Harvard Medical School
ThesisActivity-dependent regulation of Schwann cell development by extracellular ATP (2003)
Doctoral advisor
  • Roger W. Davenport
  • R. Douglas Fields
Other academic advisorsBen Barres
Notable studentsDorothy P. Schafer

Beth Stevens (born 1970) is an associate professor in the Department of Neurology at Harvard Medical School and the F. M. Kirby Neurobiology Center at Boston Children’s Hospital.[1] She has helped to identify the role of microglia and complement proteins in the "pruning" or removal of synaptic cells during brain development, and has also determined that the impaired or abnormal microglial function could be responsible for diseases like autism, schizophrenia, and Alzheimer's.[1]

In 2012, Stevens’s team published evidence that microglia 'eat' synapses, especially those that are weak and unused.[2] These findings pinned down a new role for microglia in wiring the brain, indicating that adult neural circuitry is determined not only by nerve cells but also by the brain’s immune cells. This helped to explain how the brain, which starts out with a surplus of neurons, trims some of the excess neurons away. Neuron named the paper its most influential publication of 2012.[3][4]

Early life and education

Beth Stevens was born in 1970 in Brockton, Massachusetts. Her mother taught elementary school, and her father was the school's principal.[5]

Stevens earned a B.S. in Biology from Northeastern University (1993), where she worked full-time in medical labs through Northeastern's co-op program. She earned a Ph.D. in Neuroscience from the University of Maryland, College Park (2003).[5] Stevens completed her postdoctoral fellowship with Ben Barres at the Stanford University School of Medicine in 2008.[6][7] There, she carried out research on the role of astrocytes and in synapse formation by triggering neurons to produce a protein that tags "eat-me" signals on immature synapses instead of mature ones.

Research

Currently, Stevens is a Research Associate in Neurology at Boston's Children's Hospital, Associate Professor of Neurology at Harvard Medical School, and institute member of the Broad Institute of MIT and Harvard.[8][7] She is the Principal Investigator of the Stevens Lab, which "seeks to understand how neuron-glia communication facilitates the formation, elimination and plasticity of synapses—the points of communication between neurons—during both healthy development and disease."[9] Stevens's work has led her to the discovery of different roles of microglia and their relevance in neurological diseases.

In 2007, Stevens discovered that proteins of the classical complement pathway were required for synapse elimination.[10] She has explored the role of complement components in schizophrenia,[11][12] Alzheimer's disease,[13] and glaucoma.[14]


Stevens and former postdoc Dorothy P. Schafer demonstrated that microglia participate in regulation of neuronal activity by phagocytosing complement-tagged synapses.[15] As the resident phagocytes of the central nervous system (CNS), microglia survey their local environment, clear cellular debris, and make contact with neurons to aid in synaptic pruning during development and learning.[16] They proposed a "quad-partite" expansion of the tripartite synapse model by including microglia as functional participants in developing and mature synapses.[17]

Stevens has found that microglia play a role in synapse loss in a range of disease states, including West Nile virus infection[18] and neurodegenerative diseases such as Alzheimer's disease,[13] where synapse loss precedes neuron death.[19] Microglia may contribute to disease both by phagocytosing synaptic material [13] and activating neurotoxic astrocytes.[20] Her research indicates that neurodegenerative diseases may represent a local reactivation of microglial pruning pathways that are beneficial during development but detrimental in the mature brain. Stevens has also identified microglia as a contributor to Rett syndrome progression independent of MECP2 mutation, which is known to cause the disease.[21]

Awards

Stevens has received recognition for her discoveries and is the recipient of several awards, including the following:

  • John Merck Fund[22]
  • Presidential Early Career Award for Scientists and Engineers (PECASE)[5]
  • Smith Family Award for Excellence in Biomedical Research
  • Dana Foundation Award (Brain and Immunoimaging)
  • Ellison Medical Foundation New Scholar in Aging Award
  • MacArthur Fellows Program[6]

Stevens received the MacArthur Foundation's award of $625,000 in order to continue her studies on brain cells. Out of the 24 recipients of the award only 9, including Stevens, were women.[23] Stevens received the Presidential Early Career Award for Scientists and Engineers (PECASE) in 2012, which is awarded to young scientists by the US government. In October 2015, she gave one of 4 Presidential lectures at the annual meeting of the Society for Neuroscience, the world's largest gathering of neuroscientists. She shared this honor with 3 other neuroscientists, two of which are Nobel laureates.

Stevens was named an HHMI Investigator in 2018.[24]

Personal life

Stevens is married to Rob Graham.[5]

References

  1. 1 2 "Beth Stevens". MacArthur Foundation. Retrieved 2015-09-29.
  2. Schafer, DP; Lehrman, EK; Kautzman, AG; Koyama, R; Mardinly, AR; Yamasaki, R; Ransohoff, RM; Greenberg, ME; Barres, BA; Stevens, B (2012). "Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner". Neuron. 74 (4): 691–705. doi:10.1016/j.neuron.2012.03.026. PMC 3528177. PMID 22632727.
  3. "Neuron Highlights Stevens Lab Publication in 25th Anniversary Issue". Stevens Lab. 2013-10-31. Archived from the original on 2018-08-13. Retrieved 2018-03-02.
  4. "Looking Back: Microglia in synaptic pruning". Cell. Retrieved 2015-10-14.
  5. 1 2 3 4 "Beth Stevens: Casting immune cells as brain sculptors". Spectrum News. 2015-09-24. Retrieved 2015-10-14.
  6. 1 2 "Beth Stevens". 2011-07-23. Retrieved 2015-10-14.
  7. 1 2 "Beth Stevens | Broad Institute". 2015-05-14. Retrieved 2018-03-02.
  8. "Beth Stevens, PhD | Boston Children's Hospital". Retrieved 2018-03-02.
  9. "Stevens Lab Research". 2011-07-18. Retrieved 2018-03-02.
  10. Stevens, B; Allen, NJ; Vazquez, LE; Howell, GR; Christopherson, KS; Nouri, N; Micheva, KD; Mehalow, AK; Huberman, AD; Stafford, B; Sher, A; Litke, AM; Lambris, JD; Smith, SJ; John, SW; Barres, BA (14 Dec 2007). "The classical complement cascade mediates CNS synapse elimination". Cell. 131 (6): 1164–78. doi:10.1016/j.cell.2007.10.036. PMID 18083105. S2CID 2830592.
  11. Sekar, A; Bialas, AR; de Rivera, H; Davis, A; Hammond, TR; Kamitaki, N; Tooley, K; Presumey, J; Baum, M; Van Doren, V; Genovese, G; Rose, SA; Handsaker, RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Daly, MJ; Carroll, MC; Stevens, B; McCarroll, SA (11 Feb 2016). "Schizophrenia risk from complex variation of complement component 4" (PDF). Nature. 530 (7589): 177–183. Bibcode:2016Natur.530..177.. doi:10.1038/nature16549. PMC 4752392. PMID 26814963.
  12. Håvik, B; Le Hellard, S; Rietschel, M; Lybæk, H; Djurovic, S; Mattheisen, M; Mühleisen, TW; Degenhardt, F; Priebe, L; Maier, W; Breuer, R; Schulze, TG; Agartz, I; Melle, I; Hansen, T; Bramham, CR; Nöthen, MM; Stevens, B; Werge, T; Andreassen, OA; Cichon, S; Steen, VM (1 Jul 2011). "The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia". Biol Psychiatry. 70 (1): 35–42. doi:10.1016/j.biopsych.2011.01.030. PMID 21439553. S2CID 26368229.
  13. 1 2 3 Hong, S; Beja-Glasser, VF; Nfonoyim, BM; Frouin, A; Li, S; Ramakrishnan, S; Merry, KM; Shi, Q; Rosenthal, A; Barres, BA; Lemere, CA; Selkoe, DJ; Stevens, B (6 May 2016). "Complement and microglia mediate early synapse loss in Alzheimer mouse models". Science. 352 (6286): 712–6. Bibcode:2016Sci...352..712H. doi:10.1126/science.aad8373. PMC 5094372. PMID 27033548.
  14. Howell, GR; Macalinao, DG; Sousa, GL; Walden, M; Soto, I; Kneeland, SC; Barbay, JM; King, BL; Marchant, JK; Hibbs, M; Stevens, B; Barres, BA; Clark, AF; Libby, RT; John, SW (7 Mar 2011). "Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma". J Clin Invest. 121 (4): 1429–44. doi:10.1172/JCI44646. PMC 3069778. PMID 21383504.
  15. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R; et al. (2012). "Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner". Neuron. 74 (4): 691–705. doi:10.1016/j.neuron.2012.03.026. PMC 3528177. PMID 22632727.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. Hong, Soyon; Stevens, Beth (25 Jul 2016). "Microglia: Phagocytosing to Clear, Sculpt, and Eliminate". Dev Cell. 38 (2): 126–8. doi:10.1016/j.devcel.2016.07.006. PMID 27459063.
  17. Schafer, DP; Lehrman, EK; Stevens, B (Jan 2013). "The "quad-partite" synapse: microglia-synapse interactions in the developing and mature CNS". Glia. 61 (1): 24–36. doi:10.1002/glia.22389. PMC 4082974. PMID 22829357.
  18. Vasek, MJ; Garber, C; Dorsey, D; Durrant, DM; Bollman, B; Soung, A; Yu, J; Perez-Torres, C; Frouin, A; Wilton, DK; Funk, K; DeMasters, BK; Jiang, X; Bowen, JR; Mennerick, S; Robinson, JK; Garbow, JR; Tyler, KL; Suthar, MS; Schmidt, RE; Stevens, B; Klein, RS (23 Jun 2016). "A complement-microglial axis drives synapse loss during virus-induced memory impairment". Nature. 534 (7608): 538–43. Bibcode:2016Natur.534..538V. doi:10.1038/nature18283. PMC 5452615. PMID 27337340.
  19. Stephan, AH; Barres, BA; Stevens, B (2012). "The complement system: an unexpected role in synaptic pruning during development and disease". Annu Rev Neurosci. 35: 369–89. doi:10.1146/annurev-neuro-061010-113810. PMID 22715882. S2CID 2309037.
  20. Liddelow, SA; Guttenplan, KA; Clarke, LE; Bennett, FC; Bohlen, CJ; Schirmer, L; Bennett, ML; Münch, AE; Chung, WS; Peterson, TC; Wilton, DK; Frouin, A; Napier, BA; Panicker, N; Kumar, M; Buckwalter, MS; Rowitch, DH; Dawson, VL; Dawson, TM; Stevens, B; Barres, BA (18 Jan 2017). "Neurotoxic reactive astrocytes are induced by activated microglia". Nature. 541 (7638): 481–487. Bibcode:2017Natur.541..481L. doi:10.1038/nature21029. PMC 5404890. PMID 28099414.
  21. Schafer, DP; Heller, CT; Gunner, G; Heller, M; Gordon, C; Hammond, T; Wolf, Y; Jung, S; Stevens, B (2016). "Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression". eLife. 5 (e15224): 481–487. doi:10.7554/eLife.15224. PMC 4961457. PMID 27458802.
  22. "Grant Archive - John Merck Fund". Retrieved 2018-03-02.
  23. Harrington, Rebecca (25 September 2015). "Meet the Brilliant Scientist Who Just Got $625K for Her Work on a Vital, Overlooked Part of the Brain". Tech Insider. Retrieved 2016-03-16.
  24. "HHMI Bets Big on 19 New Investigators". Retrieved 2021-10-12.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.