Steve Fancy, PhD, DVM | Newborn Brain Research Institute

Associate Professor, Neurology and Pediatrics

M_Neurology

Oligodendrocytes are the myelinating cells of the CNS that enable formation of myelin and saltatory nerve conduction. Disorders of oligodendrocytes and white matter are associated with human newborn neurological injuries leading to Cerebral palsy (CP). Damaged myelin sheaths and oligodendrocytes (OL) can be regenerated in these conditions by oligodendrocyte precursor cells (OPCs) in a process called remyelination. But myelin repair often fails, contributing significantly to ongoing neurological dysfunction and disease progression, and can fail because of failed OPC migration/recruitment into lesions or from their failed differentiation into mature OL. We have recently shown that OPCs migrate around the CNS using blood vessels as the physical scaffold for their motility, identifying critical oligodendroglial-vascular interactions that determine OPC dispersal during development and disease. Images show OPCs migrating on blood vessels in both normal human brain development and in the newborn neurological injury Hypoxic Ischemic Encephalopathy, as well as an electron micrograph of human myelin sheaths.

Publications

AEGIS reveals epitope- and clone-resolved convergence of CNS B and T cell autoreactivity in ROHHAD.

bioRxiv : the preprint server for biology

Bodansky A, Ahyong V, Dayao M, Asaki J, Vanasupa S, Dandekar R, Chen S, Sabatino J, Klauer S, Knudsen G, Lizama Valenzuela C, McCutcheon K, Zorn K, Sidhu S, Yu D, Garcia S, Quandt Z, Wang CY, Castillo Rojas B, 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, Consortium, Anderson MS, Gerdts J, Wilson MR, DeRisi JL

DNA damage burden causes selective CUX2 neuron loss in neuroinflammation.

Nature

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

Expansion of outer cortical CUX2 neurons requires adaptations for DNA repair.

Nature

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

Stretched to meet the challenge of myelination.

Neuron

Xia W, Fancy SPJ

COUNTERING AGE-ASSOCIATED ALTERATIONS IN OLIGODENDROCYTE-DERIVED EXTRACELLULAR MATRIX REJUVENATES COGNITION.

bioRxiv : the preprint server for biology

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

TGFß signaling mediates microglial resilience to spatiotemporally restricted myelin degeneration.

Nature neuroscience

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

Proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage in prenatal human brain.

Nature neuroscience

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

Author Correction: Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.

Nature medicine

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

mTOR activation induces endolysosomal remodeling and nonclassical secretion of IL-32 via exosomes in inflammatory reactive astrocytes.

Journal of neuroinflammation

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

Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.

Cell reports

Hoi KK, Xia W, Wei MM, Ulloa Navas MJ, Garcia Verdugo JM, Nachury MV, Reiter JF, Fancy SPJ

Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development.

Neuron

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

CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states.

Nature neuroscience

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

Mechanisms of oligodendrocyte progenitor developmental migration.

Developmental neurobiology

Xia W, Fancy SPJ

Oligodendroglial ring finger protein Rnf43 is an essential injury-specific regulator of oligodendrocyte maturation.

Neuron

Niu J, Yu G, Wang X, Xia W, Wang Y, Hoi KK, Mei F, Xiao L, Chan JR, Fancy SPJ

CNS fibroblasts form a fibrotic scar in response to immune cell infiltration.

Nature neuroscience

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

Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation.

Nature neuroscience

Niu J, Tsai HH, Hoi KK, Huang N, Yu G, Kim K, Baranzini SE, Xiao L, Chan JR, Fancy SPJ

Transforming growth factor-beta renders ageing microglia inhibitory to oligodendrocyte generation by CNS progenitors.

Glia

Baror R, Neumann B, Segel M, Chalut KJ, Fancy SPJ, Schafer DP, Franklin RJM

Lgl1 controls NG2 endocytic pathway to regulate oligodendrocyte differentiation and asymmetric cell division and gliomagenesis.

Nature communications

Daynac M, Chouchane M, Collins HY, Murphy NE, Andor N, Niu J, Fancy SPJ, Stallcup WB, Petritsch CK

Enhancing Oligodendrocyte Myelination Rescues Synaptic Loss and Improves Functional Recovery after Chronic Hypoxia.

Neuron

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

Clemastine rescues myelination defects and promotes functional recovery in hypoxic brain injury.

Brain : a journal of neurology

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

Fibrinogen Activates BMP Signaling in Oligodendrocyte Progenitor Cells and Inhibits Remyelination after Vascular Damage.

Neuron

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

Moderate-Grade Germinal Matrix Haemorrhage Activates Cell Division in the Neonatal Mouse Subventricular Zone.

Developmental neuroscience

Dawes WJ, Zhang X, Fancy SPJ, Rowitch D, Marino S

Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery.

eLife

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

Oligodendrocyte precursors migrate along vasculature in the developing nervous system.

Science (New York, N.Y.)

Tsai HH, Niu J, Munji R, Davalos D, Chang J, Zhang H, Tien AC, Kuo CJ, Chan JR, Daneman R, Fancy SP

Sox2 Sustains Recruitment of Oligodendrocyte Progenitor Cells following CNS Demyelination and Primes Them for Differentiation during Remyelination.

The Journal of neuroscience : the official journal of the Society for Neuroscience

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

Apcdd1 stimulates oligodendrocyte differentiation after white matter injury.

Glia

Lee HK, Laug D, Zhu W, Patel JM, Ung K, Arenkiel BR, Fancy SP, Mohila C, Deneen B

Daam2-PIP5K is a regulatory pathway for Wnt signaling and therapeutic target for remyelination in the CNS.

Neuron

Lee HK, Chaboub LS, Zhu W, Zollinger D, Rasband MN, Fancy SP, Deneen B

Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis.

Cell

Yuen TJ, Silbereis JC, Griveau A, Chang SM, Daneman R, Fancy SPJ, Zahed H, Maltepe E, Rowitch DH

Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.

Nature medicine

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

Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer.

Nature neuroscience

Fancy SP, Harrington EP, Baranzini SE, Silbereis JC, Shiow LR, Yuen TJ, Huang EJ, Lomvardas S, Rowitch DH

Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.

Glia

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

Evidence that nuclear factor IA inhibits repair after white matter injury.

Annals of neurology

Fancy SP, Glasgow SM, Finley M, Rowitch DH, Deneen B

Regional astrocyte allocation regulates CNS synaptogenesis and repair.

Science (New York, N.Y.)

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

Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination.

Proceedings of the National Academy of Sciences of the United States of America

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

Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

Huang JK, Fancy SP, Zhao C, Rowitch DH, Ffrench-Constant C, Franklin RJ

Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination.

Nature neuroscience

Fancy SP, Harrington EP, Yuen TJ, Silbereis JC, Zhao C, Baranzini SE, Bruce CC, Otero JJ, Huang EJ, Nusse R, Franklin RJ, Rowitch DH

Myelin regeneration: a recapitulation of development?

Annual review of neuroscience

Fancy SP, Chan JR, Baranzini SE, Franklin RJ, Rowitch DH

Oligodendrocyte PTEN is required for myelin and axonal integrity, not remyelination.

Annals of neurology

Harrington EP, Zhao C, Fancy SP, Kaing S, Franklin RJ, Rowitch DH

CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination.

Cell stem cell

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