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Faculty Detail    
Name MICHELLE L OLSEN
 
Campus Address MCLM 958A Zip 0005
Phone  205-975-2715
E-mail  molsen@uab.edu
Other websites Lab Website
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Assistant Professor Adjunct

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Genetics, Genomics and Bioinformatics 
Neuroscience 
Pathobiology and Molecular Medicine 

Biographical Sketch 
PhD (Neurobiology) University of Alabama at Birmingham 2005

Society Memberships
Organization Name Position Held Org Link
2000 - present Society for Neuroscience   Member   
2013 - present American Society for Neurochemistry  Member   

Research/Clinical Interest
Title
Understanding the function of astrocytes during normal and aberrant development
Description
Project 1: Kir4.1 is a glial specific inwardly rectifying potassium channel. Highest expression is observed in astrocytes. Kir4.1 demonstrates robust developmental upregulation. Although Kir4.1 is expressed in all astrocytes studied, expression levels vary over 10-fold across different brain structures in adult rodents. Kir4.1 is implicated in several critical astrocytic homeostatic functions (right). Loss of Kir4.1 protein expression leads to aberrant CNS development in humans and rodents. A focus of the Olsen lab is to understand what regulates patterns of Kir4.1 gene and protein expression in typical development, so that we can better understand how loss of this protein (seen in the context of disease) contributes to aberrant CNS functioning. Project 2: Rett Syndrome is a devastating X-linked neurodevelopmental disorder affecting 1:10,000 live female births. Girls develop seemingly normal until about 12-18 months of age when they begin to demonstrate developmental regression. Hallmarks of Rett syndrome include loss of gross motor skills, breathing abnormalities, cognitive deficits, hand stereotopies, gastrointestinal dysmotility, difficulty with ambulation and seizures. Over 95% of Rett syndrome cases are caused by spontaneous mutations in the transcriptional regulator methyl binding protein 2 (MECP2). In the CNS, MeCP2 is highly expressed in neurons, but is also expressed at lower levels in astrocytes, microglia and oligodendrocytes. A focus of the Olsen lab is to better understand astrocyte function in MeCP2 deficient astrocytes and how this contributes to overall disease onset and progression.

Selected Publications 
Publication PUBMEDID
Manuscripts

Physiology and function of the glial inwardly rectifying potassium channel Kir4.1. SE Nwaobi, VA Cuddapah, KC Patterson, AC Randolph, and ML Olsen, review, Acta Neuropathologica (2016) March
PMID: 26961251

Novel applications of magnetic cell sorting to analyze CNS cell-type specific gene and protein expression, PLos One (2016) LM Holt and ML Olsen, Feb 26;11(2)
PMID: 26919701

Emerging insight into the critical role of astrocyte ion channels in homeostasis and neuron-glia signaling. ML Olsen, B Khahk, S Skatchkov, Z Min, N Rouach, Journal of Neuroscience (2015) 14;35(41):13827-35, ·Corresponding Author
PMCID: PMC4604221

MECP2’s role in regulating neural activity: pathophysiological perspectives. VA Cuddapah, Nwaobi, SE, AK Percy, and ML Olsen, Degenerative Neurological and Neuromuscular Disease (2015) 5:103-116

Correlating gene-specific DNA methylation changes with expression and transcriptional activity of astrocytic KCNJ10 (Kir4.1), SE Nwaobi and ML Olsen, Journal of Visualized Experiments (2015) Sep(26)103
PMID 26436772

Elevated GFAP induces astrocyte dysfunction in caudal brain regions: a potential mechanism for hindbrain involved symptoms in type II Alexander Disease, HR Minkel, TZ Anwer, KM Arps, M Brenner, ML Olsen, Glia (2015) Dec;63(12)2285-97
PMID:26190408

Insufficient GLT-1 Glutamate Transport and Altered Astrocyte Biophysical Properties Contributes to Hyperexcitability in Cortical Dysplasia, , SL Campbell, JJ Hablitz and ML Olsen, Frontiers in Molecular Neuroscience (2014) Dec 17;8:425
PMID: 25565960

Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington's disease model mice, X. Tong, Y Ao, GC Faas, SE Nwaobi, J Xu, MD Haustein, MA Anderson, I Mody, ML Olsen, MV Sofroniew, BS Khakh, Nature Neuroscience (2014) May;17(5):694-703 , 2014
PMID:24686787

Methyl-CpG-binding protein 2 (MEPC2) mutation type is associated with disease severity in Rett Syndrome, VA Cuddapah, RB Pillai, KV Shekar, JB Lane, KJ Motil, SA Skinner, G McGwin, DC Tarquinio5, DG Glaze, WE Kaufmann, AK Percy, JL Neul, ML Olsen, Journal of Medical Genetics (2014) Mar;51(3):152-8 2014 This article was featured as editor’s choice
PMID 24399845

DNA methylation is a critical regulator of Kir4.1 in CNS development, SE Nwaobi, SR Peramsetty, E Lin and ML Olsen, Glia (2014) Mar;62(3):411-27, 2014
PMID:24415225

Development and validation of fluorescence- and automated patch clamp-based functional assays for the inward rectifier potassium channel Kir4.1, R Raphemot, R Kadakia, ML Olsen, S Banerjee, E Days, SS Smith, CD Weaver and JS Denton. Assay and Drug Development Technologies (2013) Nov-Dec;11(9-10):532-43
PMID: 24266659

Spinal Cord Injury in vivo Causes Wide-Spread, Persistent Loss of Kir4.1 and GLT-1: Potential Benefits of Treatment with 17-beta Estradiol, ML Olsen, SL Campbell, CL Floyd, H Sontheimer, Brain (2010) 133(Pt 4):1013-25
PMID: 20375134

Functional Implications for Kir4.1 Channels in Glial Biology: From K+ Buffering to Cell Differentiation, ML Olsen and H Sontheimer, Journal of Neurochemistry (2008) 107, 589–601
PMID:18691387

ClC3 Is a Critical Regulator of Cell Cycle in Normal and Malignant Cells, CM Habela, ML Olsen and H Sontheimer, Journal of Neuroscience (2008) 28(37):9205-17
PMID: 18784301

BK Channels are Coupled to IP3-receptors via Lipid Rafts: a Novel Mechanism for Coupling [Ca2+]i to Channel Activation, AK Weaver, ML Olsen, MB McFerrin and H Sontheimer, Journal of Biological Chemistry (2007) 26;282(43):31558-68
PMID: 17711864

Differential Distribution of Kir4.1 in Spinal Cord Astrocytes Suggests Regional Differences in K+ Homeostasis, ML Olsen, SL Campbell and H Sontheimer, Journal of Neurophysiology (2007) 98(2):786-93
PMCID: 2040512

Functional Expression of Kir4.1 Channels in Spinal Cord Astrocytes, ML Olsen, H Higashimori, SL Campbell, JJ Hablitz and H Sontheimer, Glia (2006) 53(5):516-28, cover art
PMCID: 2553202

Modulation of Glioma BK (gBK) Channels via erbB2, ML Olsen, AK Weaver, P Ritch, H Sontheimer, Journal of Neuroscience Research (2005) 15;81(2):179-89
PMID: 15948146

Mislocalization of Kir Channels in Malignant Glia, ML Olsen, H. Sontheimer, Glia (2004) 46:63-73, 200, cover art
PMCID: 2548404

Expression of Voltage-Gated Chloride Channels in Human Glioma Cells, ML Olsen, S. Schade, S.A. Lyons, M.D. Amaral, H. Sontheimer, Journal of Neuroscience (2003) 23(13)5572-5582
PMID: 12843258




Book Chapters

Voltage-Gated Ion Channels in Glial Cells, ML Olsen, H Sontheimer. Neuroglia, 2nd Edition, Oxford University Press, pp112-130, 2004

Whole-Cell Patch Clamp Recordings, Patch-Clamp Analysis: Advanced Techniques, Second Edition, H Sontheimer and ML Olsen. Humana Press, pp35-68, 2008

Ionic Channels in Glia. ML Olsen and H Sontheimer, Encyclopedia of Neuroscience, Oxford: Academic Press, volume 5, pp. 237-247. 2009 book cover art

Potassium Channel Function in Astrocytes, Astrocytes: Methods and Protocols, ML Olsen. Humana Press, Invited Review, ed. R. Milner, Springer Press, NY, 2012

Ionic Channels in Glia. Encyclopedia of Neuroscience, H Sontheimer and ML Olsen, Oxford: Academic Press, Invited update, in press, 2015
 
 

Keywords
brain injury, neurodevelopmental disorders, spinal cord, astrocyte, potassium channel, glutamate transporter, epigenetics