Dr. Nikolaus McFarland, M.D., Ph.D.

 

Dr. Niklaus McFarlandAssistant Professor of Neurology
Faculty, UF Movement Disorders Center
Investigator, Parkinson Disease and Movement Disorders Research group and CTRND

Training:
Clinical Research Fellowship in Movement Disorders, Dept Neurology at Massachusetts General Hospital and MassGeneral Institute for Neurodegenerative Disease (MIND), 2006-10
Neurology Residency/Internship, University of Virginia Health System, 2002-06
MD, University of Rochester School of Medicine & Dentistry, 2002
PhD, University of Rochester School of Medicine & Dentistry, 2001
BA, University of Chicago, 1992

 

 

Contact:
Clinic: (352) 294-5400
Office: (352) 273-5550
nikolaus.mcfarland@neurology.ufl.edu
Center for Movement Disorders and Neurorestoration Website

 

Research Focus and Aims:

My research focuses on understanding the pathological mechanisms of Parkinson disease and related disorders (atypical parkinsonisms) and in particular the role of alpha-synuclein in cell toxicity and neurodegeneration. A major hallmark of neurodegenerative disorders, including Parkinson disease, is abnormal protein aggregation and deposition. In Parkinson disease and related disorders, intracellular inclusions called Lewy bodies are found. A principal component of these Lewy bodies is alpha-synuclein. Abnormal folding, aggregation, and deposition of alpha-synuclein are believed to be central to the development of neuronal dysfunction and cell loss. A primary goal of my research is to elucidate the mechanisms of alpha-synuclein toxicity and to characterize molecular mediators that may enhance or rescue its toxicity. Our work involves use of cellular, neuronal, and preclinical models that employ alpha-synuclein overexpression and allow for testing of various genes, molecules, and compounds that may modify toxicity and have the potential for novel therapeutics. We have also recently begun studies on related neurodegenerative disorders such as PSP (Progressive Supranuclear Palsy) and ALS (Amyotrophic Lateral Sclerosis, or Lou Gehrig’s disease) in which abnormal protein misfolding and deposition also occur. Current research projects include:

  1. Rab protein and alpha-synuclein interactions: Abnormal accumulation of the protein, alpha-synuclein results in intracellular trafficking and vesicle accumulation, ER stress, and toxicity. The discovery that these deficits can be ameliorated by expression of specific Rab proteins—members of the Ras superfamily of GTP-bindings proteins—suggests that alpha-synuclein accumulation may interfere with normal Rab function. These proteins may also play an important role in preventing formation toxic synuclein aggregates. We are studying the mechanisms whereby Rab protein expression confers protection against alpha-synuclein induced toxicity in both cellular and animal models of Parkinsonism. Additional studies examine Rab protein interactions with alpha-synuclein in pathological brain specimens from Parkinson disease patients and other related disorders. (Funding: NIH K08-NS067024)
  2. RER1 (Retention in endoplasmic reticulum 1) and potential role in Parkinson disease: Increasing evidence suggests that RER1 plays a key role in regulating trafficking and maturation of certain proteins, such as amyloid beta and gamma secretase in Alzheimer’s disease (Park et al, JBC 2012). We have recently shown that RER1 also appears to reduce levels of alpha-synuclein, suggesting it may play a role in Parkinson disease. Ongoing studies investigate whether RER1 expression can prevent alpha-synuclein buildup and pathology in animal models of Parkinsonism. (Funding: Michael J. Fox Foundation)
  3. Ubiquilin2 in ALS: Recently mutations in the gene for ubiquilin2 (UBQLN2) have been linked to familial ALS. Ubiquilin2-containing protein inclusions are found not only in familial ALS cases, but also more widely in sporadic ALS/ALS-dementia cases, suggesting a pathogenic role in disease. We have recently developed cell and animal models using viral expression techniques to study the role of ubiquilin2 and ALS-linked mutants in ALS pathology.
  4. Initiative for Atypical Parkinsonism: In the Movement Disorders Clinic over the next few years we are developing a multidisciplinary group and approach to help those with Parkinson-plus syndromes, or atypical Parkinsonism such as Progressive Supranuclear Palsy (PSP) and Multiple System Atrophy (MSA). In contrast to classical Parkinson disease, these disorders often do not respond as well to dopamine therapies, progressive more rapidly, and have additional features such as frequent falls, bulbar symptoms, and cognitive decline. These disorders are also particularly challenging to caregivers. More research is clearly needed for better diagnostics and therapeutics.

References:

  1. Planetta PJ, Kurani AS, Shukla P, Prodoehl J, Corcos DM, Comella CL, McFarland NR, Okun MS, Vaillancourt DE. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Human brain mapping. 2015;36(3):1165-79.
  2. Ceballos-Diaz C, Rosario AM, Park HJ, Chakrabarty P, Sacino A, Cruz PE, Siemienski Z, Lara N, Moran C, Ravelo N, Golde TE, McFarland NR. Viral expression of ALS-linked ubiquilin-2 mutants causes inclusion pathology and behavioral deficits in mice. Molecular neurodegeneration. 2015;10:25. PMCID: 4495639.
  3. Burciu RG, Ofori E, Shukla P, Planetta PJ, Snyder AF, Li H, Hass CJ, Okun MS, McFarland NR, Vaillancourt DE. Distinct patterns of brain activity in progressive supranuclear palsy and Parkinson’s disease. Movement disorders : official journal of the Movement Disorder Society. 2015;30(9):1248-58. PMCID: 4578977.
  4. Amano S, Skinner JW, Lee HK, Stegemoller EL, Hack N, Akbar U, Vaillancourt D, McFarland NR, Hass CJ. Discriminating features of gait performance in progressive supranuclear palsy. Parkinsonism & related disorders. 2015;21(8):888-93.
  5. Planetta PJ, Kurani AS, Shukla P, Prodoehl J, Corcos DM, Comella CL, McFarland NR, Okun MS, Vaillancourt DE. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Human brain mapping. 2014.
  6. McFarland NR, Dimant H, Kibuuka L, Ebrahimi-Fakhari D, Desjardins CA, Danzer KM, Danzer M, Fan Z, Schwarzschild MA, Hirst W, McLean PJ. Chronic Treatment with Novel Small Molecule Hsp90 Inhibitors Rescues Striatal Dopamine Levels but Not alpha-Synuclein-Induced Neuronal Cell Loss. PLoS One. 2014;9(1):e86048. PMCID: 3896461.
  7. McFarland NR, Burdett T, Desjardins CA, Frosch MP, Schwarzschild MA. Postmortem Brain Levels of Urate and Precursors in Parkinson’s Disease and Related Disorders. Neurodegener Dis. 2013;12(4):189-98. PMCID: 3809155.
  8. Golde TE, Lewis J, McFarland NR. Anti-tau antibodies: hitting the target. Neuron. 2013;80(2):254-6.
  9. Dimant H, Kalia SK, Kalia LV, Zhu L, Kibuuka L, Ebrahimi-Fakhari D, McFarland NR, Fan Z, Hyman BT, McLean PJ. Detection of alpha-synuclein oligomers in vivo. Molecular Neurodegen Comm. 2013;1(6):[ePub].

 

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