Dr. Jeffrey A. Cohlberg
Professor, Biochemistry
Department Chairman
B.A., Chemistry, Cornell University, 1966
Ph. D., Biochemistry, University of California, Berkeley, 1972
Principal courses taught: Chemistry 441A/B, 443, 544, 595A
Area of research: Protein aggregation, neurofilament assembly
Phone: (562) 985-4944
e-mail: cohlberg@csulb.edu
Teaching Interests
Chem 441A/B, our introductory biochemistry lecture courses, Chem 443, our biochemistry laboratory course, and Chem 544, a graduate lecture course in physical biochemistry.
Research Interests
Protein aggregation and neurodegenerative disease:
Mutations in the enzyme Cu,Zn-superoxide dismutase (SOD1) are responsible for one type of familial amyotrophic lateral sclerosis (ALS). ALS, also called Lou Gehrig’s disease, is a type of motor neuron disease, in which various insoluble protein deposits containing SOD and other proteins are found in the neurons. The disease is not caused by a loss of superoxide dismutase activity, since some ALS-related SOD mutants are fully active. Also, since the mutations are dominant rather than recessive, the enzyme must acquire an unwanted property as a result of the mutation. One leading theory is that mutant SODs have a greater tendency to form insoluble aggregates.
SOD1 is a dimer of 16-kD polypeptide chains, each with one copper ion and one zinc ion, and each containing one intramolecular disulfide bond. Work in our lab has shown that under defined conditions SOD1 will form a type of protein aggregate called amyloid fibrils. Amyloid formation is promoted by removal of metals or by cleavage of the disulfide bond, and mutations related to ALS increase the amount and rate of amyloid formation. This work is a collaboration with the laboratory of Dr. Joan Valentine of UCLA and is supported by grants from Research Corporation and the ALS Association. We have also shown that some ALS-related mutations weaken the association of monomers to form dimers. Furthermore, we have identified some soluble intermediates in the pathway of SOD aggregation which may play a role in causing ALS.
Since becoming department chair, I have discontinued my research and am not accepting new research students.
Selected publications
Oztug Durer ZA, Cohlberg JA, Dinh P, Padua S, Ehrenclou K, Downes S, Tan JK, Nakano Y, Bowman CJ, Hoskins JL, Kwon C, Mason AZ, Rodriguez JA, Doucette PA, Shaw BF, Selverstone Valentine J. (2009) "Loss of metal ions, disulfide reduction and mutations related to familial ALS promote formation of amyloid-like aggregates from superoxide dismutase," PLoS ONE. 4(3):e5004.
Cao, X., Antonyuk, S., Seetharaman. S. V., Whitson, L. J., Taylor, A. B., Holloway, S. P., Strange, R. W., Doucette, P. A., Valentine, J. S., Tiwari, A., Hayward, L. J., Padua, S., Cohlberg, J. A., Hasnain, S. S., and Hart, P. J. (2008) "Structures of the G85R variant of SOD1 in Familial ALS," J. Biol. Chem. 283, 16169-16177.
Hull, E., Spoja, C., Cordova, M., and Cohlberg, J. A. (2008) "Neurofilament aggregation in a cell line model system," Biochemical and Biophysical Research Communications 366, 73-79
Zhang, G., Spencer, P. H., Jin, L. Q., Cohlberg, J. A., Beaulieu, J. M., Julien, J.-P., and Selzer, M. E. (2004) "The single neurofilament subunit of lamprey may need another element for filaments assembly," J. Comp. Neurol. 471, 188-200
Cohlberg, J. A., Li, J., Uversky, V. N., and Fink, A. L. (2002) "Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro," Biochemistry 41, 1502-1511.
Abumuhor, I. A., Spencer, P. H., and Cohlberg, J. A. (1998) "The pathway of assembly of intermediate filaments from recombinant alpha-internexin," Journal of Structural Biology 123, 187-198
Streifel, T. D., Avalos, R. T., and Cohlberg, J. A. (1996) "cAMP-dependent phosphorylation of neurofilament proteins NF-L and NF-M inhibits their coassembly into filaments in vitro," Biochemical and Biophysical Research Communications 222, 646-651
Cohlberg, J. A., Hajarian, H., Tran, T., Alipour-jeddi, P., and Noveen, A. (1995) "Neurofilament protein heterotetramers as assembly intermediates," Journal of Biological Chemistry 270, 9334-9339
Cohlberg, J. A. (1993) "Textbook error: the structure of alpha-keratins," Trends in Biochemical Sciences 18, 360-362
Guan, R. J., Khatra, B. S., and Cohlberg, J. A. (1991) "Phosphorylation of bovine neurofilament proteins by protein kinase FA (glycogen synthase kinase 3)," Journal of Biological Chemistry 266, 8262-8267
Cohlberg, J.A., Hajarian, H., and Sainte-Marie, S. (1987) "Discrete soluble forms of the middle and high molecular weight neurofilament proteins in dilute aqueous buffers," Journal of Biological Chemistry 262, 17009-17015
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Last updated 08/24/2009 09:37 AM
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