Kirby D. Smith, Ph.D. Image

Professor of Pediatics and Institute of Genetic Medicine

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Contact Information

Tower 4, Kennedy Krieger
443-923-2751; 443-923-2753
443-923-2775 (Fax)
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Research Interests

The Genetic Basis for Phenotypic Variability of Inherited Metabolic Diseases; Molecular Biology of the Peroxisome

The severity of adult hemoglobinopathies can be moderated by the presence of red cells containing fetal hemoglobin (F-cells). The fraction of F-cells in adults varies over a 20 fold range. We have identified a locus (FCP) on the X-chromosome that accounts for 50% of this variation. The FCP gene has been mapped to a small (<1Mb) region of Xp and its physical isolation is in progress.

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X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder with variable phenotypic expression that is characterized by elevated very long chain fatty acids. However, the product of the gene defective in X-ALD (ALDP) is a membrane transporter and is not related to enzymes that activate or oxidize fatty acids. Using genetic anlyses, we have identified an autosomal gene that in part determines the phenotypic expression of X-ALD. We are examining the function of ALDP, determining the underlying pathophysiology of the various forms of X-ALD, searching for the autosomal modifying gene and investigating the possibility of pharmcological gene therapy for peroxisomal disorders.

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Selected Publications

  • Lu JF, Lawler AM, Watkins PA, Powers JM, Moser AB, Moser HW and Smith KD. A mouse model for X-linked adrenoleukodystrophy. Proc Natl Acad Sci USA 94: 9366-9371, 1997.
  • Kemp S, Wei H-M, Lu J-F, Braiterman LT, McGuinness MC, Moser AB, Watkins PA, and Smith KD. Gene redundancy and pharmacological gene therapy: Implications for X-linked adrenoleukodystrophy. Nature Medicine 4:1261, 1998.
  • Smith KD, Kemp S, Braiterman LT, Lu J-F, Wei H-M, Geraghty M, Stetten G, Bergin JS, Pevsner J, and Watkins PA. X-Linked Adrenoleukodystrophy: Genes, Mutations, and Phenotypes. Neurochemical Research, 24:521-535, 1999.
  • Wei H, Kemp S, McGuinness MC, Moser AB, and Smith KD. Pharmacological Induction of Peroxisomes in Peroxisome Biogenesis Disorders. Annuals of Neurology 47:286-286, 2000.
  • McGuinness MC and Smith KD. Cerebral Inflammation in X-Linked Adrenoleukodystrophy. Archivum Immunologiae et Therapiae Experimentalis 47:281-287, 1999.
  • Braiterman LT, Watkins PA, Moser AB, and Smith KD. Peroxisomal Very Long Chain Fatty Acid b-Oxidation Activity Is Determined by the Level of Adrenodeukodystrophy Protein (ALDP) Expression. Molecular Genetics and Metabolism 66:91-99, 1999.
  • Lachtermacher MBR, Seu├ínez HN, Moser AB, Moser HW, and Smith KD. Determination of 30 X-Linked Adrenoleukodystrophy Mutations, Including 15 Not Previously Described. Human Mutation 15:348-353, 2000.
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