Graduate Studies Faculty

« Back to Search List

Susan Hayflick, MD

Admin Unit: SOM-Molecular & Medical Genetics Department
Molecular & Medical Genetics
Program in Molecular & Cellular Biosciences
Research Interests:
Human genetics; Neurogenetics; Genetics of eye disease; Metabolism; Mitochondrial disorders; Disorders of metal metabolism » Click here for more about Dr. Hayflick's research » PubMed Listing
Preceptor Rotations
Dr. Hayflick has not indicated availability for preceptor rotations at this time.
Faculty Mentorship
Dr. Hayflick has not indicated availability as a mentor at this time.

Brain iron accumulates in many human neurodegenerative disorders, including Parkinson disease, Alzheimer disease and HIV encephalopathy. To investigate brain iron dyshomeostasis, we study a group of rare, single gene disorders, called Neurodegeneration with Brain Iron Accumulation (NBIA). Our NBIA research has identified the first two major genes for this disorder: PANK2, which encodes a key regulatory enzyme in the biosynthesis of coenzyme A, and PLA2G6, which encodes a phospholipase A2. Both are critical in maintaining membrane integrity. Our studies of PANK2 and its protein product currently focus on cellular localization, processing and distribution in both wild type and mutant tissue. We are exploring the genetic and biochemical perturbations in this form of NBIA, called pantothenate kinase-associated neurodegeneration (PKAN), investigating the mechanism by which this enzymatic defect leads to high brain iron and other phenotypic features, delineating the range of human neurologic disease associated with this pathway, and developing rational therapies, based on our evolving understanding of the pathophysiology. Similar studies are underway on PLA2G6, identified in 2006 as the causative gene for Infantile Neuroaxonal Dystrophy (INAD) and atypical NAD. Murine KO models of both disorders have been developed to serve as a resource for genetic, biochemical, radiographic, electrophysiological, and clinical studies. We collaborate with labs at OHSU and other academic institutions, including UCSF, Stanford and the University of Birmingham.

  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. Rana A, Seinen E, Siudeja K, Muntendam R, SrinivasanB, van der Want JJ, Hayflick SJ, Reijngoud D-J, Kayser O and Sibon OCM, Pantethine rescues a Drosophila model for pantothenate kinase- associated neurodegeneration. Proceedings of the National Academy of Sciences 2010 107(15):6988-93
  8. Polster BJ, Westaway S, Yoon M, Hayflick SJ, Characterization of the human PANK2 promoter. Gene 2010 465(1-2):53-60
  9. Gregory A and Hayflick SJ, Genetics of Neurodegeneration with Brain Iron Accumulation. Current Neurology and Neuroscience Reports 2011 11(3):254-61
  10. Siudeja K, Srinivasan B, Xu L, Rana A, de Jong J, Nollen EAA, Jackowski S, Sanford L, Hayflick SJ and Sibon OCM. Impaired Coenzyme A metabolism affects histone and tubulin acetylation in a Drosophila and human cell model of the neurodegenerative disorder PKAN. EMBO Molecular Medicine 2011 3(12):755-66
  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 in press