2001 - Center for Advanced Biotechnology and Medicine - Rutgers ...

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Peter Lobel
we have produced recombinant enzyme in a form that can be taken up by affected cells in culture
to correct the primary defect. We are also working to develop a LINCL mouse model that should
allow detailed studies of disease pathophysiology and evaluation of potential therapeutics
strategies.
Another research program in the laboratory is to identify the spectrum of lysosomal enzymes
encoded by the human genome. This research is particularly timely given the current effort
towards determining the complete sequence of the human genome. Our approach is to purify
mannose 6-phosphorylated proteins and then analyze each protein by peptide mapping, mass
spectrometry, and chemical sequencing. This information is used to search sequence databases to
determine if a given protein corresponds to a known lysosomal enzyme or if it represents a
previously unidentified species. We recently used this approach to determine the molecular basis
for Niemann Pick type C2 disease, a fatal cholesterol storage disorder. In addition to their roles in
human inherited diseases, alterations in the lysosomal system have been implicated in a variety of
disease processes such as tumor invasion and metastasis in cancer, tissue destruction in arthritis,
and early changes associated with Alzheimer’s disease. Once we develop the tools to visualize
and characterize the players, our ultimate goal will be to understand the role that lysosomal
proteins play in these widespread pathological processes.
Publications:
Naureckiene, S., Sleat, D.E., Lackland, H., Fensom, A., Vanier, M.T., Wattiaux, R., Jadot, M. and
Lobel, P. (2000). Indentification of HE1 as the second gene of Niemann-Pick C disease. Science
290:2227-2229.
Sohar, I., Lin, L. and Lobel, P. (2000). Enzyme-based diagnosis of classical late infantile
neuronal ceroid lipofuscinosis: comparison of tripeptidyl peptidase I and pepstatin-insensitive
protease assays. Clin. Chem. 46:1005-1008.
Lin, L., Sohar, I., Lackland, H. and Lobel, P. (2001). The human CLN2 protein/tripeptidylpeptidase
I is a serine protease that autoactivates at acidic pH. J. Biol. Chem. 276: 2249-2255.
Sleat, D.E., Sohar, I., Gin, R.M. and Lobel, P. (2001). Aminoglycoside-mediated suppression of
nonsense mutations in late infantile neuronal ceroid lipofuscinosis. Eur. J. Paed. Neurol. 5A:45-
50.
Lin, L. and Lobel, P. (2001). Production and characterization of recombinant human CLN2
protein for enzyme replacement therapy in late infantile neuronal ceroid lipofuscinosis. Biochem.
J. 357:49-55.
Lin, L. and P. Lobel. (2001). Expression and analysis of CLN2 variants in CHO cells: Q100r
represents a polymorphism, and G389E and R447H represent loss-of-function mutations. Hum.
Mutat. 18:165.
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Center for Advanced Biotechnology and Medicine
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