Research: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, the third most frequent cause of cancer mortality and one of the most rapidly increasing cancers in America. Currently, surgery is the only effective treatment for HCC. Unfortunately, HCC is primarily asymptomatic and less than 20% of liver cancer patients are diagnosed early enough for surgery to remain an option. Major risk factors for HCC have however been identified: greater than 85% of all HCC patients have liver cirrhosis, most arising from chronic viral infection with either HBV or HCV. Roughly 3 – 7% of all patients with cirrhosis will develop HCC. Given the clearly defined populations at risk, identification and development of serum biomarkers with sufficient sensitivity and selectivity to diagnose or assist in the diagnosis of HCC early enough for surgical intervention would have significant clinical impact.
Our laboratory has two principal interests. First, we are interested in identifying novel potential biomarkers for HCC. Our second interest revolves around the recent observation that fucosylation of several serum glycoproteins increases in HCC. While the mechanism(s) involved remain unclear, preliminary observations suggest that levels of the fucosylated isoforms of at least 2 proteins (AFP and GP73) in serum are more tightly correlated with HCC than the total level of either protein. We are interested in both the mechanism and potential consequences of the accumulation of fucosylated proteins in the serum of HCC patients.
Selected Research Publications:
"Missense Mutation in Translocon Subunit Sec61 Blocks Necrosis Induced by a Hyperactivated C. elegans DEG/ENaC Channel"
Royal D., Royal M., Lizzio M., Bianchi L., Nunez U., Nefsky B., and M.A. Driscoll.
Manuscript in preparation.
"Ded1 is a DEAD Box RNA Helicase Which Interacts with both Cdc2 & Chk1"
Liu H., Nefsky B., and N. Walworth.
J. Biol. Chem., 277: 2637, 2002.
"Protein Turnover Plays a Key Role in aging"
Ryazanov A. and B. Nefsky.
Mechanisms of Ageing and Development 123, 2002
"Pub1 Acts as an E6-AP Like Protein Ubiquitin Ligase in the Degradation of Cdc25"
Nefsky B. and D. Beach.
EMBO J., 15: 1301, 1996.
"Yeast Actin is Relatively Well Behaved"
Nefsky B., and A. Bretscher.
Eur. J. Biochem., 206: 949, 1992.
"The Calmodulin & F Actin Binding Site of Smooth Muscle Caldesmon Lie in the Carboxyl Terminal Domain Whereas the Molecular Weight Heterogeneity Lies in the Middle of the Molecule"
Riseman V., Lynch W., Nefsky B., and A. Bretscher.
J. Biol. Chem., 264: 2869-2875, 1989.
"Immobilized Monomeric Actin & Its Use in the Isolation of Protease Free & Ribonuclease Free Pancreatic Deoxyribonuclease I"
Nefsky B., and A. Bretscher.
Eur. J. Biochem., 179: 215-219, 1989.
"Landmark Mapping: A General Method for Localizing Cysteine Residues within a Protein"
Nefsky B., and A. Bretscher.
Proc. Natl. Acad. Sci. U.S.A., 86: 3549, 1989.
"Studies on the NADH & NADPH Riboflavin 5' Phosphate (FMN) Oxidoreductase from Beneckea Harveyi: Characterization of the FMN Binding Site"
Nefsky B. and M. DeLuca
Arch. Biochem. Biophys., 216: 10-16, 1982.
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