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. Zhu K, Liu Y, Min JH, Joshua V, Lin J, Li Y, Kreutzmann JC, Guo Y, Xia W, Mohammadi E, Pieber M, Suerth V, Xia Y, Andrusivova Z, Hugnot JP, Kanatani S, Uhlén P, Lundeberg J, Li X, Fancy SPJ, Sarlus H, Harris RA, Lund H. Publisher Correction: TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration. Nat Neurosci. 2026 Jul; 29(7):1776. View on PubMed
  2. Bodansky A, Ahyong V, Dayao M, Asaki J, Vanasupa S, Dandekar R, Chen S, Sabatino J, Klauer S, Knudsen G, Valenzuela CL, McCutcheon K, Zorn K, Sidhu S, Yu D, Garcia S, Quandt Z, Wang CY, Rojas BC, Tilton I, Citron YR, Sharathchandra A, Gerungan C, Tomko S, Robbins NM, McKeon A, Cooper T, Harms M, Gomez R, Fancy SPJ, Green AJ, Caliskan I, Cadwell CR, Ostrem BE, Karalius M, Braun L, Gupta S, Francisco C, Peng G, Reddy AT, Nash K, Pleasure SJ, Mandel-Brehm C, Arnold TD, BRUNO Consortium, Anderson MS, Gerdts J, Wilson MR, DeRisi JL. AEGIS reveals epitope- and clone-resolved convergence of CNS B and T cell autoreactivity in ROHHAD. bioRxiv. 2026 May 11. View on PubMed
  3. Morcom L, Xia W, Xu Z, Awasthi Y, Geywitz C, Ellis MO, Noli T, Zulji A, Yamamoto D, Girdler GC, Kai L, Zhu K, Wei M, Tang XY, Hoi KK, Gonzalez-Maya J, Duncan GJ, Vaquie AM, Gold Diaz D, Kawaguchi R, Liu E, Sun Y, Yang D, Jordan GD, Lu IL, Holmqvist S, Bartels T, Ridley K, Choi JJ, Franco SJ, Huang EJ, Emery B, Geschwind D, Schirmer L, Balmus G, Popko B, Fancy SPJ, Rowitch DH. DNA damage burden causes selective CUX2 neuron loss in neuroinflammation. Nature. 2026 May; 653(8115):809-818. View on PubMed
  4. Xia W, Morcom L, Xu Z, Lu IL, Wang Q, Hoi KK, Wei M, Zhu K, Jordan G, Tang XY, Gonzalez-Maya J, Mattera VS, Panigrahi SM, Kawaguchi R, Emery B, Franco SJ, Geschwind DH, Popko B, Rowitch DH, Fancy SPJ. Expansion of outer cortical CUX2 neurons requires adaptations for DNA repair. Nature. 2026 May; 653(8115):819-830. View on PubMed
  5. Xia W, Fancy SPJ. Stretched to meet the challenge of myelination. Neuron. 2026 Feb 18; 114(4):559-561. View on PubMed
  6. Philp AR, Remesal L, Pratt KJB, Maynard JC, Sahota S, Aghayev T, Bieri G, Chu R, Avillion G, Sucharov-Costa J, Fuseya Y, Misra R, Mandelboum S, Zou B, Couthouis J, Xie XS, Fancy SPJ, Burlingame AL, Maki T, Villeda SA. COUNTERING AGE-ASSOCIATED ALTERATIONS IN OLIGODENDROCYTE-DERIVED EXTRACELLULAR MATRIX REJUVENATES COGNITION. bioRxiv. 2026 Feb 05. View on PubMed
  7. Zhu K, Liu Y, Min JH, Joshua V, Lin J, Li Y, Kreutzmann JC, Guo Y, Xia W, Mohammadi E, Pieber M, Suerth V, Xia Y, Andrusivova Z, Hugnot JP, Kanatani S, Uhlén P, Lundeberg J, Li X, Fancy SPJ, Sarlus H, Harris RA, Lund H. TGFβ signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration. Nat Neurosci. 2026 Mar; 29(3):617-631. View on PubMed
  8. Chen J, Crouch EE, Zawadzki ME, Jacobs KA, Mayo LN, Choi JJ, Lin PY, Shaikh S, Tsui J, Gonzalez-Granero S, Waller S, Kelekar A, Kang G, Valenzuela EJ, Birrueta JO, Diafos LN, Wedderburn-Pugh K, Di Marco B, Xia W, Han CZ, Coufal NG, Glass CK, Fancy SPJ, Alfonso J, Kriegstein AR, Oldham MC, Garcia-Verdugo JM, Kutys ML, Lehtinen MK, Combes AJ, Huang EJ. Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain. Nat Neurosci. 2024 Nov; 27(11):2115-2129. View on PubMed
  9. 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. Author Correction: Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis. Nat Med. 2024 Sep; 30(9):2692. View on PubMed
  10. Leng K, Rooney B, McCarthy F, Xia W, Rose IVL, Bax S, Chin M, Fathi S, Herrington KA, Leonetti M, Kao A, Fancy SPJ, Elias JE, Kampmann M. mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes. J Neuroinflammation. 2024 Aug 08; 21(1):198. View on PubMed
  11. Hoi KK, Xia W, Wei MM, Ulloa Navas MJ, Garcia Verdugo JM, Nachury MV, Reiter JF, Fancy SPJ. Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling. Cell Rep. 2023 10 31; 42(10):113272. View on PubMed
  12. 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
  13. 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
  14. Xia W, Fancy SPJ. Mechanisms of oligodendrocyte progenitor developmental migration. Dev Neurobiol. 2021 11; 81(8):985-996. View on PubMed
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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