Thomas Jefferson University - Alan Cahill, Ph.D.
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Qualifications
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Ph.D., University of London, Toxicology, 1992
B.S., University of Surrey, Biochemistry, 1988
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Expertise and Research Interests
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Expertise: biochemistry and toxicology, specializing in liver mitochondria, mitochondrial DNA, ethanol metabolism, alcoholic liver disease, aging, dietary supplementations (e.g. SAMe) and proteomics.
Research Interests:
Mitochondrial DNA, aging and alcohol consumption
Mitochondria possess their own plasmid-like genome that encodes for a number of polypeptides, tRNA molecules and rRNA molecules that are essential components of the mitochondrial protein synthetic machinery. MtDNA is replicated, transcribed and translated within the mitochondria. The co-ordination of these processes, however, and their relationship to the maintenance of the nuclear genome remain largely uncharacterized. In the liver, the continuous production of reactive oxygen species (ROS) by the electron transport chain results in the progressive oxidative modification of mtDNA accompanied by a gradual depletion over the lifetime of an organism. It is this accumulation of mtDNA oxidative damage that is believed to be one of the underlying mechanisms behind cellular aging. Chronic ethanol consumption mimics senescence in two important aspects, (i) increased mtDNA oxidation and (ii) significant mtDNA depletion. Ongoing research is attempting to elucidate the underlying molecular mechanism(s) behind these observations with the aim of developing new strategies towards treatment of alcoholic liver disease (ALD) and furthering our understanding of the intricate mechanisms involved in the aging process.
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Other Expertise
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Drug metabolism with special emphasis on novel anticancer drugs.
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Keywords
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Biochemistry; Pathology; Toxicology
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Publications
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- Cahill, A, Sykora, P., Kharbanda, K.K. and Crumm, S.E. S-Adenosyl-L-methionine co-administration prevents the ethanol-elicited dissociation of hepatic mitochondrial ribosomes in male rats. Alcoholism Clin. Exp. Res., 32, pp1-9 (2008).
- Alcoholic Liver Disease and the Mitochondrial Ribosome: Methods of Analysis by Alan Cahill & Peter Sykora in Methods in Molecular Medicine, Vol 447: Alcohol. Edited by L.E. Nagy, Humana Press Inc. Totowa, NJ, p381-394, 2008.
- Cahill A, Hershman S, Davies A, Sykora P. Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion. Am J Physiol Gastrointest Liver Physiol 289: G1115-G1123, Dec 2005
- Davies AM, Hershman S, Stabley GJ, Hoek JB, Peterson J, Cahill A. A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Nucleic Acids Research. 31(4): 1364-73, Feb 2003
- Cahill A, Cunningham CC, Adachi M, Ishii H, Bailey SM, Fromenty B, Davies A. Effects of Alcohol and Oxidative Stress on Liver Pathology: The role of the Mitochondrion. Alcoholism, Clinical and Experimental Research. 26(6): 907-915, Jun 2002
- Hoek JB, Cahill A, Pastorino JG. Alcohol and mitochondria: a dysfunctional relationship. Gastroenterology. 122(7): 2049-63, Jun 2002
- Cahill A, Cunningham CC. Effects of chronic ethanol feeding on the protein composition of mitochondrial ribosomes. Electrophoresis. 21(16): 3420-6, Oct 2000
- Pastorino JG, Marcineviciute A, Cahill A, Hoek JB. Potentiation by chronic ethanol treatment of the mitochondrial permeability transition. Biochemical and Biophysical Research Communications. 265(2): 405-9, Nov 1999
- Cahill A, Stabley GJ, Wang X, Hoek JB. Chronic ethanol consumption causes alterations in the structural integrity of mitochondrial DNA in aged rats. Hepatology. 30(4): 881-8, Oct 1999
- Vladimirova O, O''Connor J, Cahill A, Alder H, Butunoi C, Kalman B. Oxidative damage to DNA in plaques of MS brains. Multiple Sclerosis. 4(5): 413-8, Oct 1998
- Cahill A, Wang X, Hoek JB. Increased oxidative damage to mitochondrial DNA following chronic ethanol consumption. Biochemical and Biophysical Research Communications. 235(2): 286-90, Jun 1997
- Cahill A, Baio DL, Ivester P, Cunningham CC. Differential effects of chronic ethanol consumption on hepatic mitochondrial and cytoplasmic ribosomes. Alcoholism, Clinical and Experimental Research. 20(8): 1362-7, Nov 1996
- Cahill A, Baio DL, Cunningham CC. Isolation and characterization of rat liver mitochondrial ribosomes. Analytical Biochemistry. 232(1): 47-55, Nov 1995
- Cahill A, Jenkins TC, Pickering P, White IN. Genotoxic effects of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) and nitrogen mustard-N-oxide (nitromin) in Walker carcinoma cells under aerobic and hypoxic conditions. Chemico-biological Interactions. 95(1-2): 97-107, Mar 1995
- Coleman WB, Cahill A, Ivester P, Cunningham CC. Differential effects of ethanol consumption on synthesis of cytoplasmic and mitochondrial encoded subunits of the ATP synthase. Alcoholism, Clinical and Experimental Research. 18(4): 947-50, Aug 1994
- Cahill A, Jenkins TC, White IN. Metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) by purified DT-diaphorase under aerobic and anaerobic conditions. Biochemical Pharmacology. 45(2): 321-9, Jan 1993
- White IN, Cahill A, Davies A, Carthew P. Acute lesions in rats caused by 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) or nitromin: a comparison with rates of reduction in microsomal systems from target organs. Archives of Toxicology. 66(2): 100-6, 1992
- Cahill A, White IN. Reductive metabolism of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) and the induction of unscheduled DNA synthesis in rat and human derived cell lines. Carcinogenesis. 11(8): 1407-11, Aug 1990
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Individual Expertise profile of
Alan Cahill, Ph.D., Copyright © Alan Cahill, Ph.D..
Last Updated
by Alan Cahill, Ph.D. : Monday, February 9, 2009 4:55:44 PM
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