Pharmacology and Toxicology - Research

Cornelis Elferink, Ph.D.

Professor


Research Interests

The major focus of Dr. Elferink's research is the role of the aryl hydrocarbon receptor (AhR) in liver homeostasis, with an emphasis on the AhR-mediated regulation of cell cycle control. The AhR is a ligand-activated soluble transcription factor historically studied for its role in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) induced toxicity. TCDD toxicity however, represents a disruption of normal AhR functions that influence fundamental physiological processes underlying growth and differentiation. Dr Elferink has found in studies using primary liver cells and mouse models that the AhR regulates hepatocyte cell cycle control by regulating G1 phase cyclin-dependent kinase activity. The long-term objectives are to garner a mechanistic understanding of AhR activity in liver regeneration following hepatic injury. These studies hold the promise of identifying new therapeutic targets for the treatment of various liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma (HCC).

In a second research endeavor, the laboratory is actively seeking to identify serum biomarkers for early detection of HCC in Hepatitis C Virus (HCV) infected patients at-risk for developing cancer. The approach involves proteomic strategies based on 2D-difference in gel electrophoresis and stable isotope labeling coupled to mass spectrometry, and multiplexed Selected Reaction Monitoring for use in validation studies. Successful development of serum biomarkers will enhance surveillance of millions who are HCV-positive and at risk of developing HCC.

Selected Publications

Huang, G. and Elferink C. (2012) A Novel Non-Consensus Xenobiotic Response Element Capable of Mediating Aryl Hydrocarbon Receptor Dependent Gene Expression. Mol. Pharmacol. 81:338-347. - Additional Information

Sullivan, J., Croisant, S., Bambas-nolen,A., Prochaska, J., Parras, B., and Elferink, C. (2012) Building Community-Research CBPR Capacity and Incubating Partnerships Through an Environmental Justice Network/Community Science Workshop. Living Knowledge 10:12-16. - Additional Information

Mustafa, B.M., Elferink, C.J., and Petersen, J.R. (2012) HCC Biomarker, a Proteomics Approach: the Journey from Bench to Bedside. Clinical Laboratory International 36:18-20. - Additional Information

Levine-Fridman, A., Chen, L., and Elferink, C. J. (2004). Cytochrome P4501A1 Promotes G1 Phase Cell Cycle Progression by Controlling Ah Receptor Activity. Mol. Pharmacol. 65: 461-469. - Additional Information

Huang, G. and Elferink, C. J. (2005). Multiple Mechanisms are Involved in Ah Receptor Mediated Cell Cycle Arrest. Mol. Pharmacol. 67:88-96. - Additional Information

Park, K.-T., Mitchell, K., Huang, G., and Elferink, C.J. (2005) The Ah Receptor Predisposes Hepatocytes to Fas-Mediated Apoptosis. Mol. Pharmacol. 67:612-622. - Additional Information

Mitchell, K.A., Lockhart, C.A., and Elferink, C.J. (2006). Sustained Ah receptor activity attenuates liver regeneration. Mol. Pharmacol. 70:163-170. - Additional Information

Szaniszlo, P., Rose, W.A., Wang, N., Reece, L.M., Tsulaia, T.V., Hanania, E.G., Elferink, C.J. and Leary, J.F. (2006). Scanning Cytometry with a LEAP: Laser-Enabled Analysis and Processing of Live Cells In Situ. Cytometry A. 2006 Jun 28;69A(7):641-651 [Epub ahead of print] - Additional Information

Wozniak, A.L., Wang, X., Stieren, E.S., Scarbrough, S.G., Elferink, C.J. and Boehning, D. (2006). Requirement Of Biphasic Calcium Release From The Endoplasmic Reticulum For Fas-mediated Apoptosis. J. Cell. Biol. 175:709-714 - Additional Information

Mitchell, K., and Elferink, C. (2009). Timing Is Everything: Consequences of Transient and Sustained AhR Activity Biochemical Pharmacology, 77:947-956 - Additional Information

Mitchell, K., Wilson, S., and Elferink, C. (2010). The Activated Aryl Hydrocarbon Receptor Synergizes Mitogen-Induced Murine Liver Hyperplasia. Toxicology 276: 103-109 [Epub ahead of reprint] NIHMS230886. - Additional Information