Research Summary

Oligodendrocytes are the myelinating cells of the CNS that enable formation of myelin and saltatory nerve conduction. In Multiple Sclerosis (MS), the most common cause of neurological disability in young adults, myelin sheaths are lost through injury or death of mature oligodendrocytes (OL) as a result of autoimmune damage. White matter disorders are also associated with human newborn neurological injuries leading to Cerebral palsy (CP). CP complicates over 3.3/1000 live births in the United States and the incidence of this devastating condition is on the rise due to the increasing rates of survival of very low birth weight premature infants. In these conditions, myelin sheaths can be regenerated by oligodendrocyte progenitors (OLP) that are recruited to lesions and differentiate in a process called remyelination. But evidence suggests that myelin repair often fails in these diseases and this inhibition of remyelination contributes significantly to ongoing neurological dysfunction, axonal loss and disease progression. In order to understand the regulatory factors relevant in human myelin disorders, it is first critical to understand the cellular mechanisms regulating developmental myelination and the remyelination repair process following injury. My lab is a developmental biology lab, with a disease/injury repair orientation, and access to human developmental brain and MS tissue.

Major Mechanistic and Translational goals:(1) identification of novel factors critical to murine developmental myelination, a questioning of their recapitulation in adult murine remyelination, and validation in human pathological white matter injury tissue (2) gaining a greater understanding of the human white matter lesion as a dysregulated repair environment, and why myelin repair fails in human demyelinating injuries (3) identification and testing of therapeutics to promote repair in human white matter injury.

Education

Cambridge University, United Kingdom, B.A., 07/1999, Veterinary Medicine
Cambridge University, United Kingdom, M.A., 07/2004, Veterinary Medicine
Cambridge University, United Kingdom, Vet.M.B., 07/2002, Veterinary Medicine
Cambridge University, United Kingdom, Ph.D., 09/2007, Neuroscience
University of California, San Francisco, Postdoctoral, 11/2013, Neurobiology

Honors & Awards

  • 1997 & 1998
    Cambridge University 2 time winner of Cambridge Adrian Prize for veterinary medicine
  • 2003-2007
    Biotechnology and Biological Sciences Research Council UK (BBSRC) PhD Studentship award
  • 2015
    Nancy Davis Foundation Race to Erase MS Young Investigator Award
  • 2017
    Harry Weaver Scholar of the National Multiple Sclerosis Society

Selected Publications

  1. Su Y, Wang X, Yang Y, Chen L, Xia W, Hoi KK, Li H, Wang Q, Yu G, Chen X, Wang S, Wang Y, Xiao L, Verkhratsky A, Fancy SPJ, Yi C, Niu J. Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development. Neuron. 2023 01 18; 111(2):190-201.e8.  View on PubMed
  2. Leng K, Rose IVL, Kim H, Xia W, Romero-Fernandez W, Rooney B, Koontz M, Li E, Ao Y, Wang S, Krawczyk M, Tcw J, Goate A, Zhang Y, Ullian EM, Sofroniew MV, Fancy SPJ, Schrag MS, Lippmann ES, Kampmann M. CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states. Nat Neurosci. 2022 11; 25(11):1528-1542.  View on PubMed
  3. Xia W, Fancy SPJ. Mechanisms of oligodendrocyte progenitor developmental migration. Dev Neurobiol. 2021 11; 81(8):985-996.  View on PubMed
  4. Niu J, Yu G, Wang X, Xia W, Wang Y, Hoi KK, Mei F, Xiao L, Chan JR, Fancy SPJ. Oligodendroglial ring finger protein Rnf43 is an essential injury-specific regulator of oligodendrocyte maturation. Neuron. 2021 10 06; 109(19):3104-3118.e6.  View on PubMed
  5. Dorrier CE, Aran D, Haenelt EA, Sheehy RN, Hoi KK, Pintaric L, Chen Y, Lizama CO, Cautivo KM, Weiner GA, Popko B, Fancy SPJ, Arnold TD, Daneman R. CNS fibroblasts form a fibrotic scar in response to immune cell infiltration. Nat Neurosci. 2021 02; 24(2):234-244.  View on PubMed
  6. Niu J, Tsai HH, Hoi KK, Huang N, Yu G, Kim K, Baranzini SE, Xiao L, Chan JR, Fancy SPJ. Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation. Nat Neurosci. 2019 05; 22(5):709-718.  View on PubMed
  7. Baror R, Neumann B, Segel M, Chalut KJ, Fancy SPJ, Schafer DP, Franklin RJM. Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors. Glia. 2019 07; 67(7):1374-1384.  View on PubMed
  8. Daynac M, Chouchane M, Collins HY, Murphy NE, Andor N, Niu J, Fancy SPJ, Stallcup WB, Petritsch CK. Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis. Nat Commun. 2018 08 21; 9(1):2862.  View on PubMed
  9. Wang F, Yang YJ, Yang N, Chen XJ, Huang NX, Zhang J, Wu Y, Liu Z, Gao X, Li T, Pan GQ, Liu SB, Li HL, Fancy SPJ, Xiao L, Chan JR, Mei F. Enhancing Oligodendrocyte Myelination Rescues Synaptic Loss and Improves Functional Recovery after Chronic Hypoxia. Neuron. 2018 08 22; 99(4):689-701.e5.  View on PubMed
  10. Cree BAC, Niu J, Hoi KK, Zhao C, Caganap SD, Henry RG, Dao DQ, Zollinger DR, Mei F, Shen YA, Franklin RJM, Ullian EM, Xiao L, Chan JR, Fancy SPJ. Clemastine rescues myelination defects and promotes functional recovery in hypoxic brain injury. Brain. 2018 01 01; 141(1):85-98.  View on PubMed
  11. Petersen MA, Ryu JK, Chang KJ, Etxeberria A, Bardehle S, Mendiola AS, Kamau-Devers W, Fancy SPJ, Thor A, Bushong EA, Baeza-Raja B, Syme CA, Wu MD, Rios Coronado PE, Meyer-Franke A, Yahn S, Pous L, Lee JK, Schachtrup C, Lassmann H, Huang EJ, Han MH, Absinta M, Reich DS, Ellisman MH, Rowitch DH, Chan JR, Akassoglou K. Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage. Neuron. 2017 Dec 06; 96(5):1003-1012.e7.  View on PubMed
  12. Dawes WJ, Zhang X, Fancy SPJ, Rowitch D, Marino S. Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone. Dev Neurosci. 2016; 38(6):430-444.  View on PubMed
  13. Mei F, Lehmann-Horn K, Shen YA, Rankin KA, Stebbins KJ, Lorrain DS, Pekarek K, A Sagan S, Xiao L, Teuscher C, von Büdingen HC, Wess J, Lawrence JJ, Green AJ, Fancy SP, Zamvil SS, Chan JR. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery. Elife. 2016 Sep 27; 5.  View on PubMed
  14. Tsai HH, Niu J, Munji R, Davalos D, Chang J, Zhang H, Tien AC, Kuo CJ, Chan JR, Daneman R, Fancy SP. Oligodendrocyte precursors migrate along vasculature in the developing nervous system. Science. 2016 Jan 22; 351(6271):379-84.  View on PubMed
  15. Zhao C, Ma D, Zawadzka M, Fancy SP, Elis-Williams L, Bouvier G, Stockley JH, de Castro GM, Wang B, Jacobs S, Casaccia P, Franklin RJ. Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS Demyelination and Primes Them for Differentiation during Remyelination. J Neurosci. 2015 Aug 19; 35(33):11482-99.  View on PubMed
  16. Lee HK, Laug D, Zhu W, Patel JM, Ung K, Arenkiel BR, Fancy SP, Mohila C, Deneen B. Apcdd1 stimulates oligodendrocyte differentiation after white matter injury. Glia. 2015 Oct; 63(10):1840-9.  View on PubMed
  17. Lee HK, Chaboub LS, Zhu W, Zollinger D, Rasband MN, Fancy SP, Deneen B. Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS. Neuron. 2015 Mar 18; 85(6):1227-43.  View on PubMed
  18. Yuen TJ, Silbereis JC, Griveau A, Chang SM, Daneman R, Fancy SPJ, Zahed H, Maltepe E, Rowitch DH. Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis. Cell. 2014 Jul 17; 158(2):383-396.  View on PubMed
  19. Mei F, Fancy SPJ, Shen YA, Niu J, Zhao C, Presley B, Miao E, Lee S, Mayoral SR, Redmond SA, Etxeberria A, Xiao L, Franklin RJM, Green A, Hauser SL, Chan JR. Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2014 Aug; 20(8):954-960.  View on PubMed
  20. Fancy SP, Harrington EP, Baranzini SE, Silbereis JC, Shiow LR, Yuen TJ, Huang EJ, Lomvardas S, Rowitch DH. Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer. Nat Neurosci. 2014 Apr; 17(4):506-12.  View on PubMed

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