Susan Hayflick, MD
Susan Hayflick, MD - Professor and Chair
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mail Code L103
Portland, OR 97239
Office: 503 494-7703
Brain iron accumulates in many human neurodegenerative disorders, including Parkinson disease, Alzheimer disease, multiple sclerosis, and HIV encephalopathy. To investigate brain iron dyshomeostasis, we study a group of rare, single gene disorders, called Neurodegeneration with Brain Iron Accumulation (NBIA). We have identified five disease genes that underlie specific forms of NBIA. These genes encode mitochondrial proteins that are important for fatty acid metabolism, and mutations in any of these leads to a distinctive pattern of neurodegeneration and high levels of basal ganglia iron. Animal models of disease have been developed to serve as a resource for genetic, biochemical, radiographic, electrophysiological, and clinical studies. We also work with human subjects to advance understanding of disease pathogenesis since the essential features of NBIA have not been recapitulated in animal models. Much of the success of our work has depended on close and highly valued collaborations with scientists at OHSU and at other academic institutions in the US, UK, Netherlands, Italy, Japan, Australia, Canada, Dominican Republic, Spain, Portugal, France, Belgium, Poland, India, Israel and Germany.
Dr. Hayflick is part of an international consortium of scientists that has been awarded a 5.2 million euro grant to study NBIA. Read the TIRCON press release.
Online donations for NBIA Research can be made at: http://support.ohsufoundation.org/SMV14QSMNBIA
Donations can also be made check, please make check(s) payable to: OHSU Foundation Account 24315 NBIA
Mail Stop 45
PO Box 4000
Portland, OR 97208-9852
1. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J and Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nature Genetics 2001 28:4, 345-349
2. HayflickSJ, Westaway SK, Levinson B, Zhou B, Johnson MA, Ching KHL, Gitschier J. Genetic, clinical and radiographic delineation of Hallervorden Spatz syndrome. New England Journal of Medicine 2003 348(1):33-40
3. Johnson MA, Kuo YM Westaway SK, Parker SM, Gitschier J, Hayflick SJ. Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Annals of the New York Academy of Sciences 2004 1012:282-298
4. Kuo Y-M, Duncan J, Westaway SK, Yang H, Nune G, Xu EY, Hayflick SJ, Gitschier J. Deficiency of pantothenate kinase 2 in a mouse model for Hallervorden-Spatz syndrome leads to retinal degeneration and azoospermia. Human Molecular Genetics 2005 14(1):49-57.
5. Morgan NV, Westaway SK, Morton JEV, Gregory A, Gissen P, Sonek S, Cangul H, Coryell JC, Canham , Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, Wilmot B, Kramer P, Gitschier J, Maher ER, and Hayflick SJ. The calcium-independent phospholipase A2 gene, PLA2G6, is mutated in a spectrum of childhood neurodegenerative disorders with high brain iron. Nature Genetics. 2006 38(7), 752-4.
6. Gregory A, Westaway SK, Holm IE, Kotzbauer PT, Hogarth P, Sonek S, Coryell JC, Nguyen TM, Nardocci N, Zorzi G, Todriguez D, Desguerre I, Bertini E, Simonati A, Levinson B, Dias C, Barbot C, Carrilho I, Santos M, Malik I, Gitschier J and Hayflick SJ. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology 2008 71(18):1402-9
7. Kruer MC, Paisán-Ruiz C, Boddaert N, Yoon MY, Hama H, Gregory A, Malandrini A, Woltjer RL, Munnich A, Polster BJ, Palmeri S, Edvardson S, Hardy J, Houlden HH, Hayflick SJ. Defective fatty acid-2 hydroxylase leads to a novel form of NBIA. Annals of Neurology 2010 68(5):611-8
8. Polster BJ, Westaway S, Yoon M, Hayflick SJ, Characterization of the human PANK2 promoter. Gene 2010 465(1-2):53-60
9.Kruer MC, Hiken M, Gregory A, Malandrini A, Clark D, Hogarth P, Grafe M, Hayflick SJ and Woltjer RL. Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration (PKAN). Brain 2011 134(pt 4):947-58
10. Haack TB, Hogarth P, Kruer MC, Gregory A, Wieland T, Schwarzmayr T, Graf E, Sanford L, Meyer E, Kara E, Cuno SM, Harik SI, Dandu VH, Nardocci N, Zorzi G, Dunaway T, Tarnopolsky M, Skinner S, Frucht S, Hanspal E, Schrander-Stumpel C, Héron D, Mignot C, Garavaglia B, Bhatia K, Hardy J, Strom TM, Boddaert N, Houlden HH, Kurian MA, Meitinger T, Prokisch H, Hayflick SJ. Exome sequencing reveals de novo mutations in WDR45 causing a phenotypically distinct, X-linked dominant form of NBIA. 2012 Am J Hum Genet. 2012 Dec 7;91(6):1144-9
11. Hogarth P, Gregory A, Kruer MC, Sanford L, Wagoner W, Natowicz M, Egel RT, Subramony SH, Goldman J, Berry-Kravis E, Foulds NC, Desguerre I, Rodriguez D, Wilson C, Diedrich A, Green S, Tran H, Reese L, Woltjer R, and Hayflick SJ . New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. 2012. Neurology 80(3):27518.
12. Brunetti D, Dusi S, Morbin M, Uggetti A, Moda F, D’Amato I, Giordano C, d’Amati G, Cozzi A, Levi S, Hayflick S, Tiranti V. Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model. 2012. Human Molecular Genetics 21(24):5294-30517.
13. Goldman J, Berry-Kravis E, Gregory A, Hogarth P, Hayflick SJ. Clinical features of NBIA due to MPAN gene mutation. 2012. Movement Disorders In press19.
14. Hayflick SJ, Kruer MC, Gregory A, Haack TB, Kurian MA, Houlden HH, Anderson J, Boddaert N, Sanford L, Harik SI, Dandu VH, Nardocci N, Zorzi G, Dunaway T, Tarnopolsky M, Skinner S, Frucht S, Hanspal E, Schrander-Stumpel C, Mignot C, Héron D, Saunders DE, Kaminska M, Lin JP, Lascelles K, Cuno SM, Meyer E, Garavaglia B, Bhatia K, de Silva R, Crisp S, Lunt P, Hardy J, Meitinger T, Prokisch H, Hogarth P. BPAN: a new X-linked dominant disorder with brain iron accumulation. 2013. Brain In press