Research Enterprise Newsletter - September 2007: Faculty News
Pharmacology researchers Morrow and Roberts publish vitamin E study
The reported failure of vitamin E to prevent heart attacks may be due to insufficient dosing, according to a new study by Vanderbilt Department of Pharmacology faculty members L. Jackson Roberts and Jason Morrow. The findings, published online in Free Radical Biology and Medicine, suggest that earlier studies all had a fundamental flaw: The doses used weren't high enough to have a significant antioxidant effect. In fact, no studies have ever conclusively demonstrated the dose at which vitamin E can be considered an antioxidant drug, the researchers report. In their recent study, Morrow and Roberts determined the optimum antioxidant dose of vitamin E using an assay they developed to measure compounds formed by oxidative stress processes, called F2-isoprostanes. This measure, said Roberts, "has been independently validated as the best measure of oxidative stress status in vivo." Their study found that it was necessary to give at least 1600 IU per day to cause a significant reduction in oxidative stress - twice that used in some of the previous clinical trials. Based on their findings, Roberts and Morrow suggest that measures such as F2-isoprostane measurement should be incorporated into any future studies of antioxidants in atherosclerosis prevention. The study has received significant press coverage and has been discussed on more than 36 research-related web site.
Guengerich and colleagues: Enzyme tolerates mistakes in DNA
DNA is littered with "mistakes"-bases damaged by normal cellular processes or by an outside insult. These mistakes can signal for the cell to self-destruct. To survive, a cell may need to bypass such damage during replication. The bacterium Sulfolobus solfataricus produces an enzyme, called DNA polymerase IV (Dpo4), capable of bypassing 8-oxo-G, a major DNA lesion caused by oxidative damage, with high fidelity and efficiency. To determine how mutations in Dpo4 might affect its bypass ability, F. Peter Guengerich, PhD, and colleagues created mutant enzymes with variations in the amino acid residue at position 332 and characterized their activity. Their results, published as a "Paper of the Week" in the July 6 Journal of Biological Chemistry, demonstrate the importance of the bonding between the amino acid in residue 322 and the damaged DNA base in determining the fidelity and efficiency of the enzyme's bypass mechanism. Understanding such processes may aid in understanding carcinogenesis and aging, which result, in part, from DNA damage.
Anthony Forster and colleagues: on why proteins contain proline
In every form of life, proteins consist of the same 19 amino acids and just one N-alkyl amino acid, proline. Given that several N-alkyl amino acids are major products of meteorite analyses and of synthetic prebiotic experiments, why did Nature select proline? Baolin Zhang et al. investigated this question by loading various N-methyl amino acids on transfer RNAs and testing their incorporations in protein synthesis (translation). The study, entitled "Specificity of Translation for N-Alkyl Amino Acids," was published online on August 25 by the top chemistry journal, Journal of the American Chemical Society. Surprisingly, N-butyl amino acids fail to incorporate, N-methyl amino acids incorporate at variable levels, yet proline incorporates quantitatively. As the results mirror the chemical reactivities of these N-alkyl amino acids in solid-phase peptide synthesis, the authors speculate that the universal genetic code contains proline because it is more chemically reactive than other N-alkyl amino acids, even on the ribosome. The results support exploration of proline analogs and N-methyl amino acids as substrates for engineering genetically-selectable libraries of protease-resistant ligands for drug discovery.
Kennedy Center Director Presents at PWS Conference in Romania
Elisabeth Dykens, PhD, Professor of Psychology and Human Development and Director of the Vanderbilt Kennedy Center for Excellence in Developmental Disabilities, travelled to Clug-Napoca, Romania, to deliver the talk "Correlates of Behavioral Problems and Strengths in Persons With Prader-Willi Syndrome," at the 6th International Prader-Willi Scientific Conference. Dykens reported on her research findings on the adaptive and maladaptive behaviors, compulsivity, and cognitive profiles of people with Prader-Willi (PW). The talk covered her studies related to the hyperphagic drive and on ERP studies using food stimuli. She shared research findings on the measurements of both the stress and the joys of parenting a child with PW. A special emphasis was placed on the celebration of strengths of persons with PW including a desire to care-take others and an extraordinary ability to solve jigsaw puzzles. For more information on PWS research contact elizabeth.roof@vanderbilt.edu.
Obremsky and colleagues publish in major orthopaedic journal
Dr. William Obremsky and colleagues have published two articles in the Journal of Bone and Joint Surgery, the major orthopaedic journal. The first, "Preventing Perioperative Infection," was coauthored by Vanderbilt orthopedic resident Nick Fletcher and two Vanderbilt medical students, D'Mitri Sofianos and Marschaall Berkes. The article was a well-received Evidence Based Medicine review of perioperative infection prophylaxis that has already changed some OR practices. The second article, "The Introduction of Biologics in Orthopaedics," was a review of the process, economics, and ethics of new product technology into the market. Dr. Larry Churchill, Vanderbilt's Professor of Medical Ethics, was a significant contributor.
Blakely Lab News Roundup
- Dr. Solomon Snyder of the Johns Hopkins University School of Medicine will give the 2008 Babu Lecture in Membrane Biology on April 3 2008, as part of the VUMC Discovery Lecture Series. Dr. Randy D. Blakely will host.
- Dr. Shannon Hardie of the Blakely lab has received funding for her NRSA postdoctoral fellowship "Identifying Dopamine Transporter Regulator Proteins in C. elegans."
- Dr. Jeremy Veenstra-VanderWeele of the Blakely lab has received funding for his KO8 award "Murine Genetic Models of Autism."
- Dr. L. Keith Henry of the Blakely and Meiler labs has received funding for his K01 award "Integration of Computational and Biological Analyses of Serotonin Transporters."
- Brett English of the Blakely lab received an American Heart Association Predoctoral Fellowship Cardiovascular Phenotypic Consequences of Genetic Deficits in the Presynaptic Choline Transporter.
