Wendy Macklin Anschutz Cell Developmental Biology

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Wendy Macklin (Ph.D.)


Department of Cell & Developmental Biology


Oligodendrocyte Differentiation and Myelination in the Central Nervous System

Professor & Chair

Ph.D., Stanford University, 1979
M.S., Yale University, 1974

wendy.macklin@cuanschutz.edu
Phone: (303) 724.3426
Fax: (303) 724.3420

12801 E 17th Ave. 
Mail Stop 8108
Aurora, CO 80045

Graduate Program Affiliations

CSD
Cell Biology, Stem Cells and Development


Neuroscience Graduate Program

CNS
Center for Neuroscience

Signaling mechanisms that regulate oligodendrocyte differentiation and myelination.

This study focuses on the Akt/mTOR pathway in oligodendrocytes, which directly regulates the amount of CNS myelin. The downstream signaling pathways that control myelination are under investigation, with a focus on the impact of mTOR signaling on the cytoskeleton and endocytosis.

The impact of ischemia on actively myelinating oligodendrocytes.

Myelination is a highly energy dependent process but ischemia/reperfusion injury in juvenile mice has an unexpectedly small impact on myelinating oligodendrocytes. Gene expression pathways that are involved in protected oligodendrocytes from ischemic damage are actively being investigated.

Demyelination induced by antibodies cloned from multiple sclerosis patients.

How patient derived antibodies drive demyelination and alter remyelination is under active investigation. Gene expression in microglia is impacted in antibody-mediated demyelination, thereby altering remyelination.

Identification of small molecules that enhance oligodendrocyte differentiation.

This drug discovery project has identified compounds that enhance oligodendrocyte differentiation in cultured cells, and that enhance remyelination in demyelinated tissue slices in culture and in animals following in vivo demyelination. These projects have been supported for many years by grants from the NIH, the National Multiple Sclerosis Society and the American Heart Association.

Hussain R, Macklin WB. Integrin linked kinase (ILK) deletion disrupts oligodendrocyte development by altering cell cycle. J Neurosci. 2016 Dec 2. pii: 2113-16. [Epub ahead of print] PubMed PMID: 27913589.

Wood TL, Bercury KK, Cifelli SE, Mursch LE, Min J, Dai J, Macklin WB. mTOR: a link from the extracellular milieu to transcriptional regulation of oligodendrocyte development. ASN Neuro. 2013 Mar 19;5(1). doi:pii: e00108. 10.1042/AN20120092. PubMed PMID: 23421405; PubMed Central PMCID: PMC3601842.

Hu X, Schlanger R, He W, Macklin WB, Yan R. Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression. FASEB J. 2013 Jan 18. [Epub ahead of print] PubMed PMID: 23335052.

Macklin WB. The myelin brake: when enough is enough. Sci Signal. 2010 Sep 21;3(140):pe32. doi: 10.1126/scisignal.3140pe32. PubMed PMID: 20858865; PubMed Central PMCID: PMC3175620.

Mayer CA, Macklin WB, Avishai N, Balan K, Wilson CG, Miller MJ. Mutation in the myelin proteolipid protein gene alters BK and SK channel function in the caudal medulla. Respir Physiol Neurobiol. 2009 Dec 31;169(3):303-14. doi: 10.1016/j.resp.2009.09.013. Epub 2009 Oct 4. PubMed PMID: 19808102; PubMed Central PMCID: PMC3531966.

Miller MJ, Kangas CD, Macklin WB. Neuronal expression of the proteolipid protein gene in the medulla of the mouse. J Neurosci Res. 2009 Oct;87(13):2842-53. doi: 10.1002/jnr.22121. PubMed PMID: 19479988.

Narayanan SP, Flores AI, Wang F, Macklin WB. Akt signals through the mammalian target of rapamycin pathway to regulate CNS myelination. J Neurosci. 29:6860-70, 2009.

Flores AI, Narayanan SP, Morse EN, Shick HE, Yin X, Kidd G, Avila RL, Kirschner DA, Macklin WB. Constitutively active Akt induces enhanced myelination  in the CNS. J Neurosci. 28:7174-83, 2008.

Pedraza CE, Monk R, Lei J, Hao Q, Macklin WB. Production, characterization, and efficient transfection of highly pure oligodendrocyte precursor cultures from mouse embryonic neural progenitors. Glia. 56:1339-52, 2008.

Gudz TI, Komuro H, Macklin WB. Glutamate stimulates oligodendrocyte progenitor migration mediated via an alphav integrin/myelin proteolipid protein complex. J Neurosci. 26:2458-66, 2006.

Yoshida M, Macklin WB. Oligodendrocyte development and myelination in GFP-transgenic zebrafish. J Neurosci Res. 81:1-8, 2005.

Miller MJ, Haxhiu MA, Georgiadis P, Gudz TI, Kangas CD, Macklin WB. Proteolipid protein gene mutation induces altered ventilatory response to hypoxia in the myelin-deficient rat. J Neurosci. 23:2265-73, 2003.

Mallon BS, Shick HE, Kidd GJ, Macklin WB. Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical  development. J Neurosci. 22:876-85, 2002.

 

Latest Publications in PubMed

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