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Project 2

Lipid peroxidation and aging in invertebrate models

 

 

Helen Benes, Ph.D.

 

Helen Beneš, Ph.D.
Associate Professor of Neurobiology & Developmental Sciences
Associate Director, AR BRIN

 

 

                                                 Research Interests


While insects merit research as agricultural pests and vectors of disease to humans and other animals, investigations using insect models have repeatedly proven particularly valuable in elucidating basic biological processes.  For the past 10 years, research in my laboratory has focussed on the molecular and biochemical basis for aspects of insect development, with the perspective of generating novel strategies for insect control.  More recently with Dr. Piotr Zimniak (Dept. of Medicine/Gastroenterology, UAMS), my laboratory has undertaken a collaborative research project that utilizes the fruitfly, Drosophila melanogaster, to assess the role of oxidative stress and lipid peroxidation in aging of multicellular organisms.  Our collaboration includes participation in a study of transcriptional regulation of the mouse glutathione transferase gene, mGSTA4, which is specialized for the metabolism of lipid peroxidation products.  This collaboration has also led to a new area of interest, for which I intend to seek independent funding:  the role of lipid hydroperoxides as signaling molecules during development.  In sum, three major research projects in my laboratory currently utilize insect models to understand development and aging in multicellular organisms:  1) sex-specific gene activity in larval mosquitoes; 2) the role of glutathione S-transferases (GSTs) in preventing oxidative damage during aging; and 3) the role of lipid peroxidation products as signaling molecules during development. 


 

 

Principal Investigator/Program Director (Last, First, Middle):

PI Name

 

BIOGRAPHICAL SKETCH

Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person.  DO NOT EXCEED FOUR PAGES.

 

NAME

Beneš, Helen

POSITION TITLE

Associate Professor for Research, Dept. of Neurobiology & Developmental Sciences, UAMS

eRA COMMONS USER NAME 

HBENES

EDUCATION/TRAINING  (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

INSTITUTION AND LOCATION

DEGREE

(if applicable)

YEAR(s)

FIELD OF STUDY

Harvard University

B.A.

1973

French Literature Diseases

University of Arkansas for Medical Sciences

Ph.D.

1983

Anatomy/Molec. Biology

Institut J. Monod, C.N.R.S., Paris, France

Postdoctoral

1983-84

Molec. Biol./Genetics

University of Arkansas for Medical Sciences

Postdoctoral

1984-86

Molecular Biology

 

 

 

 

A.     Positions and Honors.

 

Positions and Employment

1971-1972                   Research Assistant, Dr. Fotis C. Kafatos, Harvard Biological Laboratories, Harvard University, Cambridge, MA

1974-1975                   Research Assistant, Dr. Gary L. Huber, Harvard Medical School, Boston, MA

1976                            Research Assistant, Dr. Fotis C. Kafatos, as above

1976-1977                   Research Assistant, Dr. James J. Daly, Dept. of Microbiology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR

1983-1984                   Visiting Foreign Research Associate, Dr. J.A. Lepesant, Institut Jacques Monod, Centre National de la Recherche Scientifique, Paris, France

1984-1986                   Postdoctoral Fellow, Dr. Samuel Goldstein, Dept. of Medicine, UAMS, AR

1986-1988                   Instructor, Department of Biochemistry, UAMS, Little Rock, AR

1988-1995                   Assistant Professor, Department of Biochemistry and Molecular Biology, UAMS

1991                            Visiting Foreign Research Associate, Institut J. Monod, CNRS, Paris, France

1995-2001                   Research Assistant Professor, Department of Biochemistry and Molecular

                                    Biology, UAMS

2001-2002                   Research Assistant Professor, Department of Anatomy and Neurobiology, UAMS

2002-present               Research Associate Professor, Department of Neurobiology & Developmental Sciences,

                                    UAMS

 

Other Experience and Professional Memberships

1990-present                           Member, American Society for Biochemistry and Molecular Biology

1990-1993                   Member, Committee for Equal Opportunities for Women

1990-present              Ad hoc reviewer for specialty journals (Insect Biochemistry and Molecular Biology, Insect

Molecular Biology, Archives of Insect Biochemistry and Physiology, European

Journal of Biochemistry, Aging Cell)

1992-present                           Ad hoc reviewer, USDA, Entomology & Nematology Program

1995-present                           Member, Genetics Society of America

1997-present                           Member, Entomological Society of America

2004 (Sept.)                Scientist Reviewer, Grand Challenges in Global Health, Insect Vectors Peer

Review Panel (GCGH-3)

2005 (July)                              Member, Vector Biology Study Section, NIH

 

 

 

B. Selected peer-reviewed publications (out of 31 total)

 

  1. Cherbas, L., H. Beneš, M. Bourouis, K. Burtis, A. Chao, P. Cherbas, M. Crosby, M. Gorfinkel, G. Guild, D. Hogness, J. Jami, C.W. Jones, M. Koehler, J.A. Lepesant, C. Martin, F. Maschat, P. Mathers, E. Meyerowitz, R. Moss, R. Pictet, J. Rebers, G. Richards, J. Roux, R. Schulz, W. Segraves, C. Thummel and K. Vijayraghavan (1986) Structural and functional analysis of some moulting hormone-responsive genes from Drosophila melanogaster. Insect Biochem. 16:241-248.
  2. Maschat, F., J. Roux, H. Beneš, R. Pictet, J. Jami and J.A. Lepesant (1986) Hormonal and developmental specificities of transcription lie within a 1.5 kb region 5' to the Drosophila p1 gene. EMBO J. 5:583-588.
  3. Anxolabehere, D., H. Beneš, D. Nouaud and G. Periquet (1987) The missing RP strain obtained by genetic transformation. Evolutionary steps and transposable elements in Drosophila melanogaster. Evolution 41 (3):232-240.
  4. Goldstein, S., S. Murano, H. Beneš, E.J. Moerman, R.J. Jones, R. Thweat, R. Schmookler-Reis and B.J. Howard (1989) On the molecular-genetic mechanisms of human fibroblast senescence. In Protein Metabolism and Aging (M. Rothstein, H. Segal, E. Bergamini, eds.), Alan Liss, Inc., N.Y.
  5. Goldstein, S., S. Murano, H. Beneš, E.J. Moerman, R.J. Jones, R. Thweat, R. Schmookler-Reis and B.J. Howard (1989) Studies on the molecular-genetic basis of replicative senescence in Werner syndrome and normal fibroblasts. Exp. Geront. 24:461-468.
  6. Beneš, H., R.G. Edmondson, P. Fink, J. Kejzlarova-Lepesant, J.A. Lepesant, J.P. Miles and D.W. Spivey (1990) Adult expression of the Drosophila Lsp-2 gene. Devel. Biol. 142:138-146.
  7. Antoniewski, C., M.O. O'Grady, R.G. Edmondson, S.M. Lassieur and H. Beneš (1995) Characterization of an EcR/USP heterodimer target site that mediates ecdysone responsiveness of the Drosophila Lsp-2 gene. Mol. Gen. Genet. 249(5): 545-556.
  8. Beneš, H., K.C. Neal, R.L. Willis, D. Gadde , A.B. Castleberry, and S.E. Korochkina (1996) Regulatory elements underlying larval and adult expression of the Drosophila Lsp-2 gene. Insect Molec. Biol. 5(1):39-49.
  9. Massey, H.C., J. Kejzlarova-Lepesant, R.L. Willis, A.B. Castleberry and H. Beneš (1997) The Drosophila Lsp-1gene: a structural and phylogenetic analysis. Eur. J. Biochem. 245:199-207.
  10. Zakharkin, S.O., A.V. Gordadze, S.E. Korochkina, and H. Beneš (1997) Molecular cloning and expression of an hexamerin gene from the malaria mosquito, Anopheles gambiae. Eur. J. Biochem. 246:719-726.
  11. Korochkina, S.E., A.V. Gordadze, S.O. Zakharkin, and H. Beneš (1997) Differential expression of mosquito hexamerins during metamorphosis. Insect Biochem. Molec. Biol. 27:813-824.
  12. Burmester, T., H.C. Massey, Jr., S.O. Zakharkin and H. Beneš (1998) The evolution of hexamerins and the phylogeny of insects. J. Mol. Evol. 47:93-108.
  13. Gordadze, A.V., S.E. Korochkina, S.O. Zakharkin, and H. Beneš (1999) Molecular cloning and expression analysis of two hexamerin cDNAs from A. aegypti. Insect Mol. Biol. 8:55-66.
  14. Beneš, H., R.S. Weinstein, W. Zheng, J.J. Thaden, R.L. Jilka, S.C. Manolagas and Reis, R.J.S. (2000) Chromosomal mapping of osteopenia-associated quantitative trait loci using closely related mouse strains. J. Bone Mineral Res. 15(4):626-633.
  15. Singh SP, H. Beneš, J.A. Coronella, B.J. Cochrane and P. Zimniak (2001) Drosophila melanogaster glutathione transferase conjugating 4-hydroxynonenal. Chem. Biol. Interact. 133(1-3):224-227.
  16. Singh SP, J.A. Coronella, H. Beneš, B.J. Cochrane and P. Zimniak (2001) Catalytic function of Drosophila melanogaster glutathione S-transferase DmGSTS1-1 (GST-2) in conjugation of lipid peroxidation end products. Eur. J. Biochem. 268(10):2912-23.
  17. Zakharkin, S.O., V.V. Sitnikova, N.K. Kumar, N.A. Buck, D.E. Wheeler and H. Beneš (2001) Female-specific expression of a hexamerin gene in mosquito larvae. Eur. J. Biochem. 268(22):5713-22.
  18. Sawicki, R., Singh, S.P., Mondal, A.K., Beneš, H. and P. Zimniak (2002) Cloning, expression, and biochemical characterization of one Epsilon-class (GST-3) and ten Delta-class (GST-1) glutathione S-transferases from Drosophila melanogaster, and identification of additional nine members of the Epsilon class.  Biochemical J.370(2):661-669.
  19. Zakharkin, S.O., Rebecca L. Willis, R.L., Litvinova, O.V., Jinwal, U.K., Headley, V.V., and H. Beneš(2004) Identification of two mariner-like elements in the genome of the autogenous mosquito, Ochlerotatus atropalpus. Insect Biochem. Molec. Biol. 34(4):377-386.

20.  Whitworth, A.J., D.A. Theodore, J.C. Greene, H. Beneš, P.D. Wes, and L.J. Pallanck (2005) Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease.  Proc. Natl. Acad. Sci. USA 102(22):8024-8029.

21.  Ayyadevara, S., M.R. Engle, S.P. Singh, A. Dandapat, C.F. Lichti, H. Beneš, R.J. Shmookler Reis, E. Liebau and P. Zimniak (2005) Life span and stress resistance of Caenorhabditis elegans are increased by expression of glutathione transferases capable of metabolizing the lipid peroxidation product 4-hydroxynonenal. Aging Cell 4, 257-271.

22.  Ayyadevara, S., A. Dandapat, S.P. Singh, H. Beneš, L. Zimniak, R.J. Shmookler Reis and P. Zimniak (2005) Life span extension in hypomorphic daf-2 mutants of C. elegans is partially mediated by glutathione transferase CeGSTP2-2.  Under review by Aging Cell, 9/05.

 

 

C. RESEARCH SUPPORT

 

Ongoing Research Support

R01 AI 46738-01 (H. Beneš, P.I.) 2/01/02 - 1/31/07

NIH/NIAID

Sex-specific gene activity in the mosquito larva

Major goals: To elucidate the molecular basis for sex-specific activity of the mosquito AatHex-1.2 gene, we will identify regulatory DNA sequences and transcription factor binding sites using gene transfer in Drosophila and the mosquito. Transcription factors will be characterized using nuclear extracts and cultured cells.

Role: Principal Investigator

 

R01 AG 18845-01 (P. Zimniak, P.I). 3/1/02 - 2/28/07

NIH/NIA

Role of lipid peroxidation and 4-hydroxynonenal in aging

Major goals: To create transgenic Drosophila lines with inducible and tissue-specific expression of several mammalian GSTs, some of which have the ability to conjugate 4-hydroxynonenal or to reduce lipid hydroperoxides. The lines will be used to evaluate, under normal and stressed conditions, the effects of 4-hydroxynonenal metabolism on biochemical markers of aging and on life span.

Role: Co-Investigator

 

R01 ES 07804-06 (P. Zimniak, P.I.) 8/1/96 - 7/31/06

NIH/NIEHS

Glutathione transferases and oxidative stress toxicology

Major goals: To characterize the physiological role of 4-hydroxynonenal metabolism catalyzed by mGSTA4-4 in a knockout mouse lacking the enzyme, and in transfected cells. To continue structure-function relationship studies on mGSTA4-4.

Role: Co-Investigator

 

2P20 RR16460-04A1 (L.E. Cornett, P.I.) 6/1/05 - 5/31/2010

NIH

Partnerships for Biomedical Research in Arkansas

This statewide project proposes to expand biomedical research capability within the state through support of mentored research projects, biotechnology cores, and a developing multi-campus bioinformatics graduate program.

Role: Program Coordinator

 

Completed Research Support

1-P01 AG 13918-06 (Manolagas, P.I.) 04/01/01 - 03/31/05

NIH/NIA

Molecular and Cellular Mechanisms of Osteoporosis. Molecular Genetics of Osteopenia in Senescence-Accelerated Mouse Lines (Reis, Project Leader)

Major goals: To construct genetic crosses and to map chromosome regions associated with osteopenic traits. Findings will be used to extend studies to humans.

Role: Co-Investigator

 

RR-01-005 (L.E. Cornett, P.I.) 9/30/01 - 6/30/04

NIH/NCRR

Partnerships for Biomedical Research in Arkansas

Major goals: To create the Arkansas Biomedical Research Infrastructure Network to build biomedical research capacity in Arkansas; increase the number of faculty with extramurally funded research programs, and stimulate undergraduate students to pursue careers in the biomedical sciences.

Role: Co-Investigator

 

P20 RR16460 (L.E. Cornett, P.I.) 9/30/02-6/30/04

NIH

Partnerships for Biomedical Research in Arkansas—Supplement

The supplement allows expansion of programs to develop biomedical research capacity in Arkansas.

Role:  Co-Investigator

 

P20 RR16460 (L.E. Cornett, P.I.) 9/30/02-6/30/04

NIH

Partnerships for Biomedical Research in Arkansas—Supplement

The supplement allows expansion of the bioinformatics core of the Arkansas BRIN

Role:  Co-Investigator