Medical Genetics clinical staff profiles

Parvoneh Poorkaj Navas, Ph.D.

Assistant Professor, Department of Psychiatry and Behavioral Sciences

Adjunct Assistant Professor, Division of Medical Genetics

University of Washington
Phone: (206) 616-2640
E-mail: pips@u.washington.edu

Dementia in the elderly is common, occurring in 3-5% of the population over 65 years of age. Alzheimer’s disease (AD) is the predominant cause of dementia and is responsible for 50-60% of the dementia cases in individuals over the age of 65. AD is one of a large number of heterogeneous neurological disorders which are characterized by pathological intracellular inclusions of insoluble tau proteins. These heterogeneous neurological disorders which include Frontotemporal dementia (FTD), Progressive Supranuclear Palsy (PSP), Corticobasal degeneration (CBD) and Pick’s disease (PiD) are collectively referred to as “Tauopathies”. In at least three of these Tauopathies (AD, PSP, and FTD) affected patients can also be clinically and/or pathologically affected with Parkinsonism. Dementia in these Tauopathies is caused by progressive neurodegeneration and neuronal demise, which is associated with pathology that includes neurofibrillary tangles and extracellular aggregates of amyloid and alpha-synuclein proteins. Mutations in specific genes (e.g. APP, MAPT, SNCA, and parkin) are known to cause these pathologies in familial early-onset diseases (AD, FTD, and PD, respectively); however, the genetic and/or environmental causes for sporadic cases of AD, FTD, and PD have not yet been clearly identified.

Dr. Navas’ research goals are to understand if and how complex genetic interactions between these known AD, FTD, and PD disease genes contribute to the onset, progression and variability in non-familial forms of these neurodegenerative Tauopathies. Her current research is focused on the cellular and molecular interactions of tau and parkin in neurodegeneration. Her studies seek to correlate mutation and gene dose/expression levels of MAPT and parkin with the phenotypic overlap (tangles and Parkinsonism) and diversity found in the aforementioned neurological diseases. Both in vivo and in vitro studies of the interactions between mutant and normal human MAPT and parkin are being performed. Dr. Poorkaj-Navas also collaborates with Dr. Wendy Raskind on genetic modeling of the neurological disease spinocerebellar ataxia type 14 (SCA14).

REPRESENTATIVE PUBLICATIONS:

Poorkaj P, Bird TD, Wijsman E, Nemens E, Garruto RM, Anderson L, Andreadis A, Wiederholt WC, Raskind M, Schellenberg GD: Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 1998, 43:815-825.

Bird TD, Nochlin D, Poorkaj P, Cherrier M, Kaye J, Payami H, Peskind E, Lampe TH, Nemens E, Boyer PJ, Schellenberg GD: A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 1999, 122 (Pt 4):741-56.

Poorkaj P, Muma NA, Zhukareva V, Cochran EJ, Shannon KM, Hurtig H, Koller WC, Bird TD, Trojanowski JQ, Lee VMY, Schellenberg GD: A R5L tau mutation in a subject with a progressive supranuclear palsy phenotype. Ann. Neurol. 2002, 52:511-516.

Poorkaj P, Kas A, D’Souza I, Zhou Y, Pham O, Olson MV, Schellenberg GD: A genomic sequence analysis of the mouse and human microtubule-associated protein tau . Mamm. Genome 2001, 12:700-712.

Rademakers R, Melquist S, Cruts M, Theuns J, Del-Favero J, Poorkaj P, Baker M, Sleegers K, Crook R, De Pooter T, Bel Kacem S, Adamson J, Van den Bossche D, Van den Broeck M, Gass J, Corsmit E, De Rijk P, Thomas N, Engelborghs S, Heckman M, Litvan I, Crook J, De Deyn PP, Dickson D, Schellenberg GD, Van Broeckhoven C, Hutton ML: High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy. Hum Mol Genet 2005, 14:3281-92.

Poorkaj P, Nutt JG, James D, Gancher S, Bird TD, Steinbart E, Schellenberg GD, Payami H: parkin mutation analysis in clinic patients with early-onset Parkinson's disease. Am J Med Genet A 2004, 129:44-50.

Poorkaj P, Moses L, Montimurro JS, Nutt JG, Schellenberg GD, Payami H: parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism. BMC Neurol 2005, 5:4.

Kay, D.M., Moran, D., Moses, L., Poorkaj, P., Zabetian, C.P., Nutt, J., Factor, S.A., Yu, C.E., Montimurro, J.S., Keefe, R.G., Schellenberg, G.D. and Payami, H. (2007) Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients. Ann Neurol. 2007 Jan; 61(1):47-54.

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