Medical Student Research Fellowship for Summer 2007

Mentor: Sandy Hofmann
Department: Internal Medicine
Room number: NB8.104
Mail Code: 8593
Phone number: 214-648-4911
E-mail: Sandra.hofmann@utsouthwestern.edu
Project title: Molecular Basis of Infantile Batten Disease

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic research (some contact with animals tissues may be involved)

Brief Description of Project:

Batten disease is a neurodegenerative disorder of children characterized by blindness, motor and cognitive deterioration, and eventual death caused by lack of a lysosomal enzyme discovered in the lab, palmitoyl-protein thioesterase. Current work in the laboratory seeks to understand how deficiency in the enzyme leads to neuronal cell loss, in order to develop effective therapies for the disorder.

Previous Research Activities or Publications with Medical Students:

Camp, L.A., and Hofmann, S.L. Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J. Biol. Chem. 268: 22566-22574 (1993).

Camp, L.A., Verkruyse, L.A., Afendis, S.J., Slaughter, C.S. and Hofmann, S.L. Molecular cloning and expression of palmitoyl-protein thioesterase. J. Biol. Chem. 269: 23212-23219 (1994).

Vesa, J., Hellsten, E., Verkruyse, L. A., Camp, L. A., Rapola, J., Santavuori, P., Hofmann, S.L., and Peltonen, L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature 376: 584-587 (1995).

Verkruyse, L.A. and Hofmann, S.L. Lysosomal targeting of palmitoyl-protein thioesterase. J. Biol. Chem. 271: 15831-15836 (1996).

Lu, J.-Y., Verkruyse, L.A., and Hofmann, S.L. Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis: Correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase. Proc. Natl. Acad. Sci. U.S.A. 93: 10046-10050 (1996).

Verkruyse, L.A., Natowicz, M.R, and Hofmann, S.L. Palmitoyl-protein thioesterase deficiency in fibroblasts of individuals with infantile neuronal ceroid lipofuscinosis and I-cell disease. Biochim. Biophys. Acta 1361:1-5 (1997).

Waliany, S., Das, A. K., Gaben, A., Wisniewski, K. E., Hofmann, S. L. Identification of three novel mutations of the palmitoyl-protein thioesterase (PPT1) gene in children with neuronal ceroid lipofuscinosis. Hum. Mutat. 15:206-207 (2000).

Lu, J.-Y., Verkruyse, L. A., and Hofmann, S. L. The effects of lysosomotropic agents on normal and INCL cells provide further evidence for the lysosomal nature of palmitoyl-protein thioesterase function. Biochim. Biophys. Acta 1583(1):35-44 (2002).

Virmani, T., Gupta, P., Liu, X., Kavalali, E.T. and Hofmann, S. L. Progressively reduced synaptic vesicle pool size in cultured neurons derived from neuronal ceroid lipofuscinosis-1 knockout mice. Neurobiol. Dis. 20: 314-323 (2005).

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