The major emphasis in the laboratory is on the covalent lipid modifications of proteins. This work has led to the discovery of a new lysosomal enzyme, palmitoyl-protein thioesterase, that is defective in a neuronal degenerative disorder, infantile neuronal ceroid lipofuscinosis. This disease has been considered to be a model for aging because lipofuscinosis occurs in all tissues with advancing age in normal people. Current work involves the enzymology and molecular genetics of this and related enzymes and how deficiencies in lysosomal thioesterases leads to neuronal death.
RESEARCH INTERESTS
Protein Lipidation
Neuronal Ceroid Lipofuscinosis (Batten Disease)
Oncogenesis
RECENT PUBLICATIONS
Lu, J-Y and Hofmann, SL, "Lysosomal metabolism of lipid-modified proteins" J. Lipid Res., , in press.
Virmani, T, Gupta, P, Liu, X, Kavalali, ET and Hofmann, SL, "Progressively reduced synaptic vesicle pool size in cultured neurons derived from neuronal ceroid lipofuscinosis-1 knockout mice" Neurobiol. Dis., 20:314-323, November 2005
Cho, SK and Hofmann, SL, "pdf-1, a palmitoyl protein thioesterase 1 ortholog in Schizosaccharomyces pombe: a yeast model of infantile Batten disease" Eukaryot. Cell, 3:302-10, April 2004
Gupta, P, Soyombo, AA, Shelton, JM, Wilkofsky, IG, Wisniewski, KE, Richardson, JA and Hofmann, SL, "Disruption of PPT2 in mice causes an unusual lysosomal storage disorder with neurovisceral features" Proc. Natl. Acad. Sci. U.S.A., 100:12325-30, October 2003
Calero GA, Gupta P, Nonato MC, Tandel S, Biehl ER, Hofmann SL, Clardy J,, "The crystal structure of palmitoyl protein thioesterase-2 reveals the basis for divergent substrate specificities of the two lysosomal thioesterases (PPT1 and PPT2)" J. Biol. Chem., 278:37957-64, September 2003
SIGNIFICANT PUBLICATIONS
Soyombo AA, Hofmann SL, "Molecular cloning and expression of PPT2, a homolog of lysosomal palmitoyl-protein thioesterase with a distinct substrate specificity" J. Biol. Chem., 272:27456-63, 1997
Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L., "Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis" Nature, 376:584-7, 1995
Camp LA, Hofmann SL., "Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras" J. Biol. Chem., 268:22566-74, 1993
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