University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Stephen Fancy, PhD, DVM

Stephen Fancy, PhD, DVM

Assistant Professor, Dept. of Pediatrics, UCSF

Cancer Center Program Memberships

Neurologic Oncology | Pediatric Malignancies

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


Professional Experience

  • 2007-2011
    Postdoctoral Scholar, Rowitch Lab, UCSF
  • 2011-2013
    Assistant Research Neurobiologist, Rowitch Lab, UCSF
  • 2013-present
    Assistant Professor in Residence, UCSF

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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. Molofsky AV, Glasgow SM, Chaboub LS, Tsai HH, Murnen AT, Kelley KW, Fancy SP, Yuen TJ, Madireddy L, Baranzini S, Deneen B, Rowitch DH, Oldham MC. Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions. Glia. 2013 Sep; 61(9):1518-32.
    View on PubMed
  11. Fancy SP, Glasgow SM, Finley M, Rowitch DH, Deneen B. Evidence that nuclear factor IA inhibits repair after white matter injury. Ann Neurol. 2012 Aug; 72(2):224-33.
    View on PubMed
  12. Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, Tenney A, Murnen AT, Fancy SP, Merkle F, Kessaris N, Alvarez-Buylla A, Richardson WD, Rowitch DH. Regional astrocyte allocation regulates CNS synaptogenesis and repair. Science. 2012 Jul 20; 337(6092):358-62.
    View on PubMed
  13. Chong SY, Rosenberg SS, Fancy SP, Zhao C, Shen YA, Hahn AT, McGee AW, Xu X, Zheng B, Zhang LI, Rowitch DH, Franklin RJ, Lu QR, Chan JR. Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination. Proc Natl Acad Sci U S A. 2012 Jan 24; 109(4):1299-304.
    View on PubMed
  14. Huang JK, Fancy SP, Zhao C, Rowitch DH, Ffrench-Constant C, Franklin RJ. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells. Neurotherapeutics. 2011 Oct; 8(4):650-8.
    View on PubMed
  15. Fancy SP, Harrington EP, Yuen TJ, Silbereis JC, Zhao C, Baranzini SE, Bruce CC, Otero JJ, Huang EJ, Nusse R, Franklin RJ, Rowitch DH. Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination. Nat Neurosci. 2011 Jun 26; 14(8):1009-16.
    View on PubMed
  16. Fancy SP, Chan JR, Baranzini SE, Franklin RJ, Rowitch DH. Myelin regeneration: a recapitulation of development? Annu Rev Neurosci. 2011; 34:21-43.
    View on PubMed
  17. Harrington EP, Zhao C, Fancy SP, Kaing S, Franklin RJ, Rowitch DH. Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination. Ann Neurol. 2010 Nov; 68(5):703-16.
    View on PubMed
  18. Zawadzka M, Rivers LE, Fancy SP, Zhao C, Tripathi R, Jamen F, Young K, Goncharevich A, Pohl H, Rizzi M, Rowitch DH, Kessaris N, Suter U, Richardson WD, Franklin RJ. CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell. 2010 Jun 04; 6(6):578-90.
    View on PubMed
  19. Fancy SP, Kotter MR, Harrington EP, Huang JK, Zhao C, Rowitch DH, Franklin RJ. Overcoming remyelination failure in multiple sclerosis and other myelin disorders. Exp Neurol. 2010 Sep; 225(1):18-23.
    View on PubMed
  20. Zhao C, Fancy SP, Franklin RJ, ffrench-Constant C. Up-regulation of oligodendrocyte precursor cell alphaV integrin and its extracellular ligands during central nervous system remyelination. J Neurosci Res. 2009 Nov 15; 87(15):3447-55.
    View on PubMed

Go to UCSF Profiles, powered by CTSI