Karen McFarland, Ph.D.
Phone: (352) 273-5550
Fax: (352) 273-5989
Department of Neurology
1600 SW Archer Road, R4-146
Gainesville, FL 32610-0236
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder and the result of a non-coding, pentanucleotide repeat expansion in intron 9 of the ATAXIN 10 (ATXN10) gene. SCA10 belongs with a growing group of neurological and neuromuscular disorders that are caused by microsatellite repeat expansions in non-coding regions of various genes. These diseases include myotonic dystrophy types 1 and 2 (DM1, DM2), fragile X tremor/ataxia syndrome (FXTAS), amyotrophic lateral sclerosis with frontal temporal dementia (ALS-FTD) and multiple types of spinocerebellar ataxias (SCAs).
SCA10 patients typically present with progressive cerebellar ataxia and a small percentage of these patients also present with epileptic seizures. These seizures significantly contribute to the morbidity and mortality of disease pathogenesis. However, the factors that cause some SCA10 patients to develop epilepsy are largely unknown and a subject of intense scrutiny in our lab.
We are also interested in studying the pathogenic mechanism whereby the ATTCT pentanucleotide repeat expansion causes disease. During ATXN10 mRNA production, the ATTCT genomic repeat, which can be expanded up to 4500 repeats in some SCA10 patients, is transcribed and spliced out properly; however, the resulting AUUCU-containing intron is not degraded and accumulates into RNA foci containing the RNA-binding protein hnRNP K. By understanding this mechanism and the implications of hnRNP K-AUUCU RNA binding, we hope to develop rational treatments in order to mitigate the disease process.
2004 – Ph.D., Biology, Program in Cellular, Developmental and Molecular Biology, University of Rochester, Rochester, NY.
1999 – M.S., Biology, Program in Cellular, Developmental and Molecular Biology, University of Rochester, Rochester, NY.
1997 – B.S. Biology, Magna Cum Laude, concentration in Molecular Biology, King’s College, Wilkes-Barre, PA.
Research Assistant Professor, Department of Neurology, University of Florida, Gainesville, FL. – 2010 – present
Postdoctoral Research Fellow, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Department of Neurology, Charlestown, MA. Laboratory of Jang-Ho Cha, M.D., Ph.D. – 2007 – 2010
Postdoctoral Research Associate, University of Virginia, Department of Pathology (Neuropathology), Charlottesville, VA. Laboratory of James W. Mandell, M.D., Ph.D. – 2004 – 2006
Graduate Student, University of Rochester, Rochester, NY, Department of Biology. Laboratory of Donald A. Kane, Ph.D. – 1997 – 2004
Seminar Preview Leader, Neuroscience Graduate Program, University of Virginia, Charlottesville, VA. – 2005
Co-Instructor, Current Topics in Neuroscience, University of Virginia, Neuroscience Graduate Program, Charlottesville, VA. – 2005
Teaching Assistant, Molecular Genetics Laboratory, University of Rochester, Department of Biology, Rochester, NY. – 1997 – 1998
Student Laboratory Aide, Vertebrate Biology & Cell and Developmental Biology Courses, King’s College, Wilkes-Barre, PA. -1996 – 1997
Honors & Awards
Best Other Movement Disorder (OMD) Abstract, 23rd Annual Symposium on the Etiology, Pathogenesis, and Treatment of Parkinson’s Disease and Other Movement Disorders, Baltimore, MD. – 2009
Best Basic Science Poster, University of Virginia, Department of Pathology Research Retreat, Charlottesville, VA. – 2004
Holtfreter Graduate Student Fellowship, University of Rochester, Department of Biology, Rochester, NY. – 1997 – 2001
Graduate Student Presentation Award, University of Rochester, Department of Biology, Rochester, NY. – 2000
Graduate Student Teaching Award, University of Rochester, Department of Biology, Rochester, NY. – 1999
NSF Research Experience for Undergraduates (REU) Fellowship, Undergraduate Student, Duquesne University, Department of Biology, Pittsburgh, PA. – 1996
Member, Alpha Epsilon Delta Premedical Honor Society, King’s College, Pennsylvania Lambda Chapter – 1996 – 1997
Society for Neuroscience
- White M, Xia G, Gao R, Wakamiya M, Sarkar PS, McFarland K, Ashizawa T. (2011) Transgenic mice with SCA10 pentanucleotide repeats show motor phenotype and susceptibility to seizure: A toxic RNA gain-of-function model. J Neurosci Res. 2012 Mar;90(3):706-14. PMID: 22065565.
- McFarland KN and Cha J-HJ. (2011) The molecular biology of Huntington’s disease. The Handbook of Clinical Neurology. 100: 25-81. PMID: 21496570
- Riley BB, Sweet EM, Heck R, Evans A, McFarland KN, Warga RM and Kane DA. (2010) Characterization of harpy/Rca1/emi1 mutants: Patterning in the absence of cell division. Dev Dyn. 239(3):828-843. PMID: 20146251; PMCID: PMC3086590.
- Benn CL, Sun T, Sadri-Vakili G, McFarland KN, DiRocco DP, Yohrling GJ, Clark TW, Bouzou B, Cha J-HJ. (2008) Huntingtin modulates transcription, occupies gene promoters in vivo and binds directly to DNA in a polyglutamine dependent manner. J. Neuroscience 28(42):10720-33. PMID: 18923047; PMCID: PMC2586288.
- McFarland KN, Wilkes SR, Koss SE, Ravichandran KS and Mandell JW. (2006) Neural-specific inactivation of ShcA results in increased embryonic neural progenitor apoptosis and microcephaly. J Neuroscience 26(30): 7885-7897. PMID: 16870734.
- Kane DA, McFarland KN and Warga RM. (2005) Mutations in half baked/E-cadherin block cell behaviors that are necessary for teleost epiboly. Development 132(5): 1105-1116. PMID: 15689372.
- McFarland KN, Warga RM and Kane DA. (2005) The genetic locus half baked is necessary for morphogenesis of the ectoderm. Dev Dynamic 233(2): 390-406. PMID: 15768401.