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Duane Eichler,  Ph.D.
Interim Chair, College of Medicine-Dept. of Molecular Medicine
Prevention Research Fellow, Florida Prevention Research Center (FPRC)
Basic Science Director, Cardiovascular Signature Research Program
Co-Director, Training and Professional Education Unit
Unit Director, Clinical Research and Health Management
Professor (Joint Appointment), Department of Pediatrics, College of Medicine
Professor, Department of Biochemistry and Molecular Biology, College of Medicine


Primary Department: COLLEGE OF MEDICINE MOLECULAR MEDICINE

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Contacts
Email: deichler@health.usf.edu
Phone: (813) 974-9716
Office: MDC, 3537
Mailing address 12901 Bruce B. Downs Blvd. MDC 7
Tampa, FL 33612
 
Education
  • PHD, Biological Chemistry, University Of California At Los Angeles , Los Angeles, United States - 1973.
  • B.A., Chemistry (Conc in BIochemistry), San Jose State University ,USA - 1968.
  •  
    Interdisciplinary & Emerging Signature Programs
    Cardiovascular.
     
    Research Summary

    CENTRAL HYPOTHESIS - We hypothesize that in accordance with the strict temporal and spatial control of NO production in vascular endothelial cells, argininosuccinate synthase, the rate-limiting step of the citrulline-NO cycle, is coordinately and tightly regulated via translational and posttranslational mechanisms, in addition to transcriptional regulation. This premise underlies the rationale for the specific aims our present research which focuses on posttranscriptional events that regulate AS function. First, we hypothesize that the determinants of AS subcellular localization are AS-interacting proteins which guide AS to distinct destinations within the cell. Methodology used to examine this hypothesis employs: 1) immunofluorescence microscopy; 2) pull-down analysis; 3) immunoprecipitation analysis; 4) tandem affinity purification analysis; 5) mass-spectrometry; and 6) NO determinations. Second, we hypothesize that a small protein encoded by an upstream open reading frame (uORF) represses AS mRNA translation under stress conditions by routing stalled AS mRNA particles into discrete cytoplasmic foci known as stress granules. To test this hypothesis we employ: 1) in vitro translation; 2) RNA immunoprecipitation; 3) RNA EMSA; 4) polysome profiling; 5) immunofluorescence microscopy; 6) western blotting; and 7) fluorescence in situ hybridization (FISH). Third, we hypothesize that endothelial AS protein is phosphorylated at serine/theronine residues which mediate an acute response, altering AS activity. To test this hypothesis the following methodology has been employed: 1) proteomics and mass-spectrometry; 2) mutational analysis; 3) NO determinations; 4) AS activity assays; and 5) western blotting. Fourth, to translate our cell culture work to a whole animal system, we are studying how changes in AS expression correlate with impaired vascular endothelial NO production in a diabetic rat model system. Experimental approaches include: 1) animal model characterization; 2) real time RT-PCR; 3) western blotting; 4) NO measurements; 5) immunofluorescence microscopy; and 6) FISH. Overall, results from this research have the potential to distinguish new therapeutic targets to be used to prevent or inhibit vascular endothelial dysfunction found in diabetes, obesity and other related vascular diseases.

     


    Selected Publications
  • Bansal, V.Rodriguez, P.Wu, G.Eichler, DC.Zabaleta, J.Taheri, F.Ochoa, JB. Citrulline can preserve proliferation and prevent the loss of CD3 zeta chain under conditions of low arginine. JPEN. Journal of parenteral and enteral nutrition. 28(6): 423-30, .
  • Flam, BR.Eichler, DC.Solomonson, LP. Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle. Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society. 17(3-4): 115-21, .
  • Haines, RJ.Pendleton, LC.Eichler, DC. Argininosuccinate synthase: at the center of arginine metabolism. International journal of biochemistry and molecular biology. 2(1): 8-23, 2011.
  • Goodwin, BL.Corbin, KD.Pendleton, LC.Levy, MM.Solomonson, LP.Eichler, DC. Troglitazone up-regulates vascular endothelial argininosuccinate synthase. Biochemical and biophysical research communications. 370(2): 254-8, 2008.
  • Goodwin, BL.Pendleton, LC.Levy, MM.Solomonson, LP.Eichler, DC. Tumor necrosis factor-alpha reduces argininosuccinate synthase expression and nitric oxide production in aortic endothelial cells. American journal of physiology. Heart and circulatory physiology. 293(2): H1115-21, 2007.
  • Pendleton, LC.Goodwin, BL.Solomonson, LP.Eichler, DC. Regulation of endothelial argininosuccinate synthase expression and NO production by an upstream open reading frame. The Journal of biological chemistry. 280(25): 24252-60, 2005.
  • Goodwin, BL.Solomonson, LP.Eichler, DC. Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. The Journal of biological chemistry. 279(18): 18353-60, 2004.
  • Patel, NA.Eichler, DC.Chappell, DS.Illingworth, PA.Chalfant, CE.Yamamoto, M.Dean, NM.Wyatt, JR.Mebert, K.Watson, JE.Cooper, DR. The protein kinase C beta II exon confers mRNA instability in the presence of high glucose concentrations. The Journal of biological chemistry. 278(2): 1149-57, 2003.
  • Solomonson, LP.Flam, BR.Pendleton, LC.Goodwin, BL.Eichler, DC. The caveolar nitric oxide synthase/arginine regeneration system for NO production in endothelial cells. The Journal of experimental biology. 206(Pt 12): 2083-7, 2003.
  • Diamond, FB.Eichler, DC. Leptin and the adipocyte endocrine system. Critical reviews in clinical laboratory sciences. 39(4-5): 499-525, 2002.
  • Pendleton, LC.Goodwin, BL.Flam, BR.Solomonson, LP.Eichler, DC. Endothelial argininosuccinate synthase mRNA 5'-untranslated region diversity. Infrastructure for tissue-specific expression. The Journal of biological chemistry. 277(28): 25363-9, 2002.
  • Patel, NA.Chalfant, CE.Watson, JE.Wyatt, JR.Dean, NM.Eichler, DC.Cooper, DR. Insulin regulates alternative splicing of protein kinase C beta II through a phosphatidylinositol 3-kinase-dependent pathway involving the nuclear serine/arginine-rich splicing factor, SRp40, in skeletal muscle cells. The Journal of biological chemistry. 276(25): 22648-54, 2001.
  • Flam, BR.Hartmann, PJ.Harrell-Booth, M.Solomonson, LP.Eichler, DC. Caveolar localization of arginine regeneration enzymes, argininosuccinate synthase, and lyase, with endothelial nitric oxide synthase. Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society. 5(2): 187-97, 2001.
  • Hellermann, GR.Flam, BR.Eichler, DC.Solomonson, LP. Stimulation of receptor-mediated nitric oxide production by vanadate. Arteriosclerosis, thrombosis, and vascular biology. 20(9): 2045-50, 2000.
  • Eichler, DC.Root, AW.Duckett, G.Moore, KL.Diamond, FB. A spun-column assay for determination of leptin binding in serum. Analytical biochemistry. 267(1): 100-3, 1999.
  • Patel, NA.Chalfant, CE.Yamamoto, M.Watson, JE.Eichler, DC.Cooper, DR. Acute hyperglycemia regulates transcription and posttranscriptional stability of PKCbetaII mRNA in vascular smooth muscle cells. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 13(1): 103-13, 1999.
  • Diamond, FB.Eichler, DC. Leptin: molecular biology, physiology, and relevance to pediatric practice. Advances in pediatrics. 46(): 151-87, 1999.
  • Chalfant, CE.Watson, JE.Bisnauth, LD.Kang, JB.Patel, N.Obeid, LM.Eichler, DC.Cooper, DR. Insulin regulates protein kinase CbetaII expression through enhanced exon inclusion in L6 skeletal muscle cells. A novel mechanism of insulin- and insulin-like growth factor-i-induced 5' splice site selection. The Journal of biological chemistry. 273(2): 910-6, 1998.
  • Diamond, FB.Eichler, DC.Duckett, G.Jorgensen, EV.Shulman, D.Root, AW. Demonstration of a leptin binding factor in human serum. Biochemical and biophysical research communications. 233(3): 818-22, 1997.
  • Eichler, DC. Characterization of a nucleolar 2'-O-methyltransferase and its involvement in the methylation of mouse precursor ribosomal RNA. Biochimie. 76(12): 1115-22, 1994.
  • Eichler, DC.Craig, N. Processing of eukaryotic ribosomal RNA. Progress in nucleic acid research and molecular biology. 49(): 197-239, 1994.
  • Eichler, DC.Liberatore, JA.Shumard, CM. Selection of a preribosomal RNA processing site by a nucleolar endoribonuclease involves formation of a stable complex. Nucleic acids research. 21(24): 5775-81, 1993.
  • Eichler, DC. Information processing and gene expression. The Journal of the Florida Medical Association. 80(1): 63-6, 1993.
  • Segal, DM.Eichler, DC. A nucleolar 2'-O-methyltransferase. Specificity and evidence for its role in the methylation of mouse 28 S precursor ribosomal RNA. The Journal of biological chemistry. 266(36): 24385-9, 1991.
  • Shumard, CM.Torres, C.Eichler, DC. In vitro processing at the 3'-terminal region of pre-18S rRNA by a nucleolar endoribonuclease. Molecular and cellular biology. 10(8): 3868-72, 1990.
  • Segal, DM.Eichler, DC. The specificity of interaction between S-adenosyl-L-methionine and a nucleolar 2'-O-methyltransferase. Archives of biochemistry and biophysics. 275(2): 334-43, 1989.
  • Shumard, CM.Eichler, DC. Ribosomal RNA processing. Limited cleavages of mouse preribosomal RNA by a nucleolar endoribonuclease include the early +650 processing site. The Journal of biological chemistry. 263(36): 19346-52, 1988.
  • Eichler, DC.Eales, SJ. Specificity of a nucleolar 2'-O-methyltransferase for RNA substrates. Biochemical and biophysical research communications. 155(1): 530-7, 1988.
  • Eichler, DC.Solomonson, LP.Barber, MJ.McCreery, MJ.Ness, GC. Radiation inactivation analysis of enzymes. Effect of free radical scavengers on apparent target sizes. The Journal of biological chemistry. 262(20): 9433-6, 1987.
  • Eichler, DC.Raber, NK.Shumard, CM.Eales, SJ. Isolation and characterization of a nucleolar 2'-O-methyltransferase from Ehrlich ascites tumor cells. Biochemistry. 26(6): 1639-44, 1987.
  • Barber, MJ.Eichler, DC.Solomonson, LP.Ackrell, BA. Anti-flavin antibodies. The Biochemical journal. 242(1): 89-95, 1987.
  • Ness, GC.Sample, CE.Smith, M.Pendleton, LC.Eichler, DC. Characteristics of rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The Biochemical journal. 233(1): 167-72, 1986.
  • Barber, MJ.Solomonson, LP.Eichler, DC. Spin-labeled erythrocyte membranes: direct identification of nitroxide-conjugated proteins. Biochemical and biophysical research communications. 127(3): 793-8, 1985.
  • Eichler, DC.Eales, SJ. Purification and properties of a novel nucleolar exoribonuclease capable of degrading both single-stranded and double-stranded RNA. Biochemistry. 24(3): 686-91, 1985.
  • Eichler, DC.Barber, MJ.Solomonson, LP. Anti-nitroxide immunoglobulin G: analysis of antibody specificity and their application as probes for spin-labeled proteins. Biochemistry. 24(5): 1181-6, 1985.
  • Lasater, LS.Eichler, DC. Isolation and properties of a single-strand 5'----3' exoribonuclease from Ehrlich ascites tumor cell nucleoli. Biochemistry. 23(19): 4367-73, 1984.
  • Eichler, DC.Eales, SJ. The effect of RNA secondary structure on the action of a nucleolar endoribonuclease. The Journal of biological chemistry. 258(16): 10049-53, 1983.
  • Eichler, DC.Eales, SJ. Isolation and characterization of a single-stranded specific endoribonuclease from Ehrlich cell nucleoli. The Journal of biological chemistry. 257(23): 14384-9, 1982.
  • Saporta, S.Eichler, DC. Conjugated dimers of horseradish peroxidase as neuroanatomical tracers. Brain research. 250(1): 149-53, 1982.
  • Eichler, DC.Tatar, TF.Lasater, LS. Effect of human placental ribonuclease inhibitor in cell-free ribosomal RNA synthesis. Biochemical and biophysical research communications. 101(2): 396-403, 1981.
  • Eichler, DC.Tatar, TF. Properties of a purified nucleolar ribonuclease from Ehrlich ascites carcinoma cells. Biochemistry. 19(13): 3016-22, 1980.
  • Eichler, DC.Wang, TS.Clayton, DA.Korn, D. In vitro replication of mitochondrial DNA. Elongation of the endogenous primer sequence in D loop mitochondrial DNA by human DNA polymerase beta. The Journal of biological chemistry. 252(21): 7888-93, 1977.
  • Wang, TS.Eichler, DC.Korn, D. Effect of Mn2+ on the in vitro activity of human deoxyribonucleic acid polymerase beta. Biochemistry. 16(22): 4927-34, 1977.
  • Eichler, DC.Fisher, PA.Korn, D. Effect of calcium on the recovery and distribution of DNA polymerase alpha from cultured human cells. The Journal of biological chemistry. 252(11): 4011-4, 1977.
  • Eichler, DC.Lehman, IR. On the role of ATP in phosphodiester bond hydrolysis catalyzed by the recBC deoxyribonuclease of Escherichia coli. The Journal of biological chemistry. 252(2): 499-503, 1977.
  • Uyemura, D.Eichler, DC.Lehman, IR. Biochemical characterization of mutant forms of DNA polymerase I from Escherichia coli. II. The polAex1 mutation. The Journal of biological chemistry. 251(13): 4085-9, 1976.
  • Glitz, DG.Eichler, DC.Angel, L. On the use of polyacrylamide gel electrophoresis in the analysis of the action of free and insolubilized nucleases on bacteriophage RNA. Analytical biochemistry. 62(2): 552-67, 1974.
  • Glitz, DG.Eichler, DC. Characterization of a guanylic acid specific ribonuclease from Aspergillus fumigatus. Biochemistry. 11(10): 1746-54, 1972.

  • Positions Held
  • Member (Institute for Biomolecular Science, University of South Florida 1985 - 2002)
  • Associate Professor (Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida 1983 - 1988)
  • Assistant Professor (Department of Biochemistry, College of Medicine, University of South Florida 1977 - 1983)


  • Memberships
  • American Heart Association (Member, 2007 - Present)
  • North American Association for the Study of Obesity (Member, 2007 - Present)
  • The RNA Society (Member, 2007 - Present)
  • American Society of Biological Chemists (Member, 2007 - Present)
  • H. Lee Moffitt Cancer Center & Research Institute (Member, 2007 - Present)
  • American Society of Microbiology (Member , 2007 - Present)
  • Institute for Biomolecular Science (Member, 2007 - Present)


  • Awards/Honors
  • Medical Education Award, Department of Molecular Medicine (USF College of Medicine, Tampa, FL - 2007)
  • Silver Performance Award for Outstanding Contributions 2006/2007 (USF College of Medicine, Tampa, FL - 2007)
  • Honorary Member of the Golden Key International Honor Society (University of South Florida, Tampa, FL - 2006)
  • Outstanding Contribution to the Program in Undergraduate Medical Education (USF College of Medicine, Tampa, FL - 2003)
  • Presidents Award for Faculty Excellence (USF College of Medicine, Tampa, FL - 2003)
  • Outstanding Contribution to the Program of Undergraduate Medical Education (USF College of Medicine, Tampa, FL - 2001)
  • Professorial Excellence Program Award, 1998-1999. (USF College of Medicine, Tampa, FL - 1999)
  • Distinguished Teacher Award (1996), presented from the Medical Class of 1996. (USF College of Medicine, Tampa, FL - 1996)
  • Outstanding Advisor Award from the Association of Medical Science Graduate Students (USF College of Medicine, Tampa, FL - 1991)
  • The Jerome Krivanek Distinguished Teacher Award (University of South Florida, Tampa, FL - 1991)
  • Outstanding Pre-Clinical Professor (USF College of Medicine, Tampa, FL - 1990)
  • Fellow of the Jane Coffin Childs Memorial Fund for Medical Research (Stanford University, Standord, Calif - 1972)
  • Margaret B. Kraatz Cancer Award for Outstanding Graduate Student Research (UCLA, Los Angeles, Calif - 1972)
  • Graduated with Great Distinction (San Jose State University, San Jose, California - 1968)


  • Patents & Licensing
  • Polynucleotide Targeted Against the Extended 5'-UTR Region of Argininosuccinate Synthase and Uses Th (USF#-04A060PRC - 2006)


  • Profile last modified on 03/20/2012