Dr. Alan Cahill

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Thomas Jefferson University
Pathology, Anatomy & Cell Biology
Associate Professor

Mailing Address

Thomas Jefferson University
Dept. of Pathology
Philadelphia, Pennsylvania 19107-5587
United States

Contact Information

Phone: (215) 955-0630
Fax: (215) 955-5058
Alan.Cahill@jefferson.edu

Qualifications

Ph.D., University of London, Toxicology, 1992.
B.S., University of Surrey, Biochemistry, 1988.

Expertise and Research Interests

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.

Other Expertise

Drug metabolism with special emphasis on novel anticancer drugs.

Future Research

Effects of mitochondrial DNA depletion on the apoptotic process
Mechanisms controling mitochondrial DNA replication
Effect of aging upon mitochondrial DNA replication
Caloric restriction and aging
Mitochondrial DNA and cancer
Effects of ethanol on assembly of mitochondrial ribosomes

Keywords

COS Keywords:

Biochemistry, Pathology, Toxicology.

Additional Terms:

Mitochondria, Mitochondrial DNA.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)

Memberships

Research Society of Alcoholism
The Mitochondrial Research Society

Previous Positions

1996-1997, Postdoctoral Fellow, Thomas Jefferson University, Pathology, Anatomy & Cell Biology
1994-1996, Instructor, Bowman Gray School of Medicine, Biochemistry
1992-1994, Postdoctoral Fellow, Bowman Gray School of Medicine, Biochemistry

Funding Received

  • NIH/NIAAA: Mitochondrial rRNA methylation: effects of ethanol and SAMe, 500,000, Sep 30, 2002 to Aug 31, 2005.
  • NIAAA: Chronic ethanolconsumption and mitochondrial DNA damage, 1,072,686, Sep 19, 2000 to Jun 30, 2005.
  • NIAAA: Chronic Ethanol Feeding and the Mitochondrial Ribosomal Proteins, $500,000, 2008 to 2010.

Publications

  • Sykora P, Kharbanda KK, Crumm SE, Cahill A (Sep 2008) S-Adenosyl-L-Methionine Co-administration Prevents the Ethanol-Elicited Dissociation of Hepatic Mitochondrial Ribosomes in Male Rats., Alcoholism, clinical and experimental research Abstract
  • Cahill A, Sykora P (2008) Alcoholic liver disease and the mitochondrial ribosome: methods of analysis., Methods in molecular biology (Clifton, N.J.), 447, 381-94 Abstract
  • Cahill A, Hershman S, Davies A, Sykora P (Dec 2005) Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion., American journal of physiology. Gastrointestinal and liver physiology, 289 (6), G1115-23 Abstract
  • 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, February 2003 Abstract
  • 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, June 2002
  • Hoek JB, Cahill A, Pastorino JG, Alcohol and mitochondria: a dysfunctional relationship, Gastroenterology, 122(7), 2049-63, June 2002 Abstract
  • Cahill A, Cunningham CC, Effects of chronic ethanol feeding on the protein composition of mitochondrial ribosomes, Electrophoresis, 21(16), 3420-6, October 2000 Abstract
  • 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, November 1999 Abstract
  • 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, October 1999 Abstract
  • 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, October 1998 Abstract
  • 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, June 1997 Abstract
  • 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, November 1996 Abstract
  • Cahill A, Baio DL, Cunningham CC, Isolation and characterization of rat liver mitochondrial ribosomes, Analytical Biochemistry, 232(1), 47-55, November 1995 Abstract
  • 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, March 1995 Abstract
  • 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, August 1994 Abstract
  • 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, January 1993 Abstract
  • 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 Abstract
  • 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, August 1990 Abstract

Profile Details

Last Updated: 10/6/2008

COS Expertise ID #942192
Reference this profile directly: http://myprofile.cos.com/cahill2