Iain Cartwright

Iain L. Cartwright

Associate Professor of Molecular Genetics and Associate Dean of Graduate Education, College of Medicine

Professional Summary

Research in the Cartwright laboratory addresses important questions related to mechanism in the interaction of arsenic with biological tissues by bringing new ideas, new approaches and new models to this field of toxicological research.  We have chosen to innovate by exploiting a genetically highly amenable, but non-traditional, model organism (i.e., Drosophila) to help shed new light on an important field of investigation, given our contemporary appreciation of the pathological consequences of long term exposure to low levels of this globally distributed environmental hazard. The extremely conserved nature of large numbers of genes and pathways relative to human cells, as well as its unique range of genetic tools, has made Drosophila an important experimental model for numerous human diseases.  A major publication using these approaches (Muniz Ortiz et al. (2009) Toxicol. Sci. 107:416-426) was the subject of a “Toxicological Highlight” editorial (Thomas, D. (2009) Toxicol. Sci. 107:309-311), and underscored the value of pursuing an unbiased genetic approach to uncover an essential, conserved in vivo pathway (for glutathione biosynthesis) through which eukaryotic cells can maintain homeostasis in the face of electrophilic insult by arsenic.  We have gone on to describe the generation of a transgenic model for studying the biological consequences of metabolic arsenic methylation (Muniz Ortiz et al. (2011) Toxicol. Sci. 121:303-311); this model forms one essential foundation upon which are based our current efforts aimed at using the versatile genetics of Drosophila to identify arsenic-sensitive biochemical and/or physiological pathways via functional toxicogenomic approaches, for which this higher eukaryotic organism is particularly well-suited (Cartwright, 2013, in press).  Additional, cytogenetic, advantages are inherent to this fly system also, and we are embarked on a collaborative project to investigate the effects of arsenic (and its methylated metabolites) on stem cell homeostasis in the intestinal mucosa, one of the first biological entities that arsenic encounters as it enters the tissues of any organism that has ingested it.  A further interest lies in analyzing the range of cellular proteins capable of tightly binding various arsenic species, a surprisingly overlooked area of arsenic research given the reactivity of arsenic, particularly in its methylated +3 valence form.  We have discovered in this group a highly significant over-representation of specialized proteins (chaperones and others) involved in maintaining and facilitating protein homeostasis upon proteotoxic stress (resident in both the ER and the cytosol), strongly indicative of the suggestion that enhanced proteotoxicity occurs in the presence of arsenic, and which could be a potential source of long term pathological consequences (as seen in well-known protein malfolding/aggregation syndromes affecting neural tissues).  In these various endeavors we have enlisted collaboration from highly respected investigators who can bring their particular skills (e.g., in cell biology, in proteomics, in analytical chemistry) to bear on the problems outlined, several of which represent questions of central importance regarding mechanistic aspects of cellular-arsenic interactions.

Education

Doctoral Degree, University of Warwick Coventry, England, 1979 (Biological Sciences)

Master's Degree, Oxford University Oxford, England, 1976 (Chemistry)

Master's Degree, University of Warwick Coventry, England, 1975 (Molecular Enzymology)

Bachelor's Degree, Oxford University Oxford, England, 1973 (Chemistry)

Research and Practice Interests

Research in the Cartwright laboratory addresses important questions related to mechanism in the interaction of arsenic with biological tissues by bringing new ideas, new approaches and new models to this field of toxicological research.  We have chosen to innovate by exploiting a genetically highly amenable, but non-traditional, model organism (i.e., Drosophila) to help shed new light on an important field of investigation, given our contemporary appreciation of the pathological consequences of long term exposure to low levels of this globally distributed environmental hazard. The extremely conserved nature of large numbers of genes and pathways relative to human cells, as well as its unique range of genetic tools, has made Drosophila an important experimental model for numerous human diseases.  A major publication using these approaches (Muniz Ortiz et al. (2009) Toxicol. Sci. 107:416-426) was the subject of a “Toxicological Highlight” editorial (Thomas, D. (2009) Toxicol. Sci. 107:309-311), and underscored the value of pursuing an unbiased genetic approach to uncover an essential, conserved in vivo pathway (for glutathione biosynthesis) through which eukaryotic cells can maintain homeostasis in the face of electrophilic insult by arsenic.  We have gone on to describe the generation of a transgenic model for studying the biological consequences of metabolic arsenic methylation (Muniz Ortiz et al. (2011) Toxicol. Sci. 121:303-311); this model forms one essential foundation upon which are based our current efforts aimed at using the versatile genetics of Drosophila to identify arsenic-sensitive biochemical and/or physiological pathways via functional toxicogenomic approaches, for which this higher eukaryotic organism is particularly well-suited (Cartwright, 2013, in press).  Additional, cytogenetic, advantages are inherent to this fly system also, and we are embarked on a collaborative project to investigate the effects of arsenic (and its methylated metabolites) on stem cell homeostasis in the intestinal mucosa, one of the first biological entities that arsenic encounters as it enters the tissues of any organism that has ingested it.  A further interest lies in analyzing the range of cellular proteins capable of tightly binding various arsenic species, a surprisingly overlooked area of arsenic research given the reactivity of arsenic, particularly in its methylated +3 valence form.  We have discovered in this group a highly significant over-representation of specialized proteins (chaperones and others) involved in maintaining and facilitating protein homeostasis upon proteotoxic stress (resident in both the ER and the cytosol), strongly indicative of the suggestion that enhanced proteotoxicity occurs in the presence of arsenic, and which could be a potential source of long term pathological consequences (as seen in well-known protein malfolding/aggregation syndromes affecting neural tissues).  In these various endeavors we have enlisted collaboration from highly respected investigators who can bring their particular skills (e.g., in cell biology, in proteomics, in analytical chemistry) to bear on the problems outlined, several of which represent questions of central importance regarding mechanistic aspects of cellular-arsenic interactions.

Research Support

Grant: #5-R21-ES-11009-02-A0-S0-E0 Investigators:Cartwright, Iain 06-01-2001 -05-31-2004 National Institute of Environmental Health Sciences Environmental Stability of Heritable Chromatin States Role:PI $306,000.00 Closed Level:Federal

Grant: #R21 ES017235 Investigators:Cartwright, Iain; Caruso, Joseph 07-01-2009 -06-30-2012 National Institute of Environmental Health Sciences Exploring Arsenic and its Metabolites in a Transgenic Model Role:PI $406,210.00 Closed Level:Federal

Publications

Peer Reviewed Publications

States, J Christopher; Barchowsky, Aaron; Cartwright, Iain L; Reichard, John F; Futscher, Bernard W; Lantz, R Clark (2011. ) Arsenic toxicology: translating between experimental models and human pathology.Environmental health perspectives, , 119 (10 ) ,1356-63

Muñiz Ortiz, Jorge G; Shang, Junjun; Catron, Brittany; Landero, Julio; Caruso, Joseph A; Cartwright, Iain L (2011. ) A transgenic Drosophila model for arsenic methylation suggests a metabolic rationale for differential dose-dependent toxicity endpoints.Toxicological sciences : an official journal of the Society of Toxicology, , 121 (2 ) ,303-11

Ortiz, Jorge G Muñiz; Opoka, Robert; Kane, Daniel; Cartwright, Iain L (2009. ) Investigating arsenic susceptibility from a genetic perspective in Drosophila reveals a key role for glutathione synthetase.Toxicological sciences : an official journal of the Society of Toxicology, , 107 (2 ) ,416-26

Polak, Michal; Kroeger, David E; Cartwright, Iain L; Ponce deLeon, Claudia (2004. ) Genotype-specific responses of fluctuating asymmetry and of preadult survival to the effects of lead and temperature stress in Drosophila melanogaster. Environmental pollution (Barking, Essex : 1987), , 127 (1 ) ,145-55

Polak, Michal; Opoka, Robert; Cartwright, Iain L (2002. ) Response of fluctuating asymmetry to arsenic toxicity: support for the developmental selection hypothesis. Environmental pollution (Barking, Essex : 1987), , 118 (1 ) ,19-28

Nenoi, M; Ichimura, S; Mita, K; Yukawa, O; Cartwright, I L (2001. ) Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer research, , 61 (15 ) ,5885-94

Pile, L A; Cartwright, I L (2000. ) GAGA factor-dependent transcription and establishment of DNase hypersensitivity are independent and unrelated events in vivo. The Journal of biological chemistry, , 275 (2 ) ,1398-404

Cartwright, I L; Cryderman, D E; Gilmour, D S; Pile, L A; Wallrath, L L; Weber, J A; Elgin, S C (1999. ) Analysis of Drosophila chromatin structure in vivo. Methods in enzymology, , 304 ,462-96

Nenoi, M; Cartwright, I L; Mita, K; Ichimura, S (1996. ) Comparison of the 5' upstream region of the evolutionarily equivalent polyubiquitin gene of humans and Chinese hamsters. Gene, , 179 (2 ) ,297-9

Nenoi, M; Mita, K; Ichimura, S; Cartwright, I L; Takahashi, E; Yamauchi, M; Tsuji, H (1996. ) Heterogeneous structure of the polyubiquitin gene UbC of HeLa S3 cells. Gene, , 175 (1-2 ) ,179-85

Rogulski, K R; Cartwright, I L (1995. ) Multiple interacting elements delineate an ecdysone-dependent regulatory region with secondary responsive character.Journal of molecular biology, , 249 (2 ) ,298-318

Jupe, E R; Sinden, R R; Cartwright, I L (1995. ) Specialized chromatin structure domain boundary elements flanking a Drosophila heat shock gene locus are under torsional strain in vivo. Biochemistry, , 34 (8 ) ,2628-33

Noël, P; Cartwright, I L (1994. ) A Sec62p-related component of the secretory protein translocon from Drosophila displays developmentally complex behavior. The EMBO journal, , 13 (22 ) ,5253-61

Nenoi, M; Mita, K; Ichimura, S; Cartwright, I L (1994. ) Novel structure of a Chinese hamster polyubiquitin gene. Biochimica et biophysica acta, , 1204 (2 ) ,271-8

Jupe, E R; Sinden, R R; Cartwright, I L (1993. ) Stably maintained microdomain of localized unrestrained supercoiling at a Drosophila heat shock gene locus. The EMBO journal, , 12 (3 ) ,1067-75

Cartwright, I L; Kelly, S E (1991. ) Probing the nature of chromosomal DNA-protein contacts by in vivo footprinting. BioTechniques, , 11 (2 ) ,188-90, 192-4, 196 p

Cartwright, I L; Elgin, S C (1989. ) Nonenzymatic cleavage of chromatin. Methods in enzymology, , 170 ,359-69

Kelly, S E; Cartwright, I L (1989. ) Perturbation of chromatin architecture on ecdysterone induction of Drosophila melanogaster small heat shock protein genes. Molecular and cellular biology, , 9 (1 ) ,332-5

Cartwright, I L (1987. ) Developmental switch in chromatin structure associated with alternate promoter usage in the Drosophila melanogaster alcohol dehydrogenase gene. The EMBO journal, , 6 (10 ) ,3097-101

Cartwright, I L; Elgin, S C (1986. ) Nucleosomal instability and induction of new upstream protein-DNA associations accompany activation of four small heat shock protein genes in Drosophila melanogaster. Molecular and cellular biology, , 6 (3 ) ,779-91

Eissenberg, J C; Cartwright, I L; Thomas, G H; Elgin, S C (1985. ) Selected topics in chromatin structure.Annual review of genetics, , 19 ,485-536

Cartwright, I L; Elgin, S C (1984. ) Chemical footprinting of 5S RNA chromatin in embryos of Drosophila melanogaster. The EMBO journal, , 3 (13 ) ,3101-8

Selleck, S B; Elgin, S C; Cartwright, I L (1984. ) Supercoil-dependent features of DNA structure at Drosophila locus 67B1. Journal of molecular biology, , 178 (1 ) ,17-33

Lowenhaupt, K; Cartwright, I L; Keene, M A; Zimmerman, J L; Elgin, S C (1983. ) Chromatin structure in pre- and postblastula embryos of Drosophila. Developmental biology, , 99 (1 ) ,194-201

Cartwright, I L; Hertzberg, R P; Dervan, P B; Elgin, S C (1983. ) Cleavage of chromatin with methidiumpropyl-EDTA . iron(II). Proceedings of the National Academy of Sciences of the United States of America, , 80 (11 ) ,3213-7

Elgin, S C; Cartwright, I L; Fleischmann, G; Lowenhaupt, K; Keene, M A (1983. ) Cleavage reagents as probes of DNA sequence organization and chromatin structure: Drosophila melanogaster locus 67B1. Cold Spring Harbor symposia on quantitative biology, , 47 Pt 1 ,529-38

Cartwright, I L; Elgin, S C (1982. ) Analysis of chromatin structure and DNA sequence organization: use of the 1,10-phenanthroline-cuprous complex. Nucleic acids research, , 10 (19 ) ,5835-52

Cartwright, I L; Abmayr, S M; Fleischmann, G; Lowenhaupt, K; Elgin, S C; Keene, M A; Howard, G C (1982. ) Chromatin structure and gene activity: the role of nonhistone chromosomal proteins. CRC critical reviews in biochemistry, , 13 (1 ) ,1-86

Cartwright, I L; Hutchinson, D W (1980. ) Azidopolynucleotides as photoaffinity reagents. Nucleic acids research, , 8 (7 ) ,1675-91

Bendall, M R; Cartwright, I L; Clark, P I; Lowe, G; Nurse, D (1977. ) Inhibition of papain by N-acyl-aminoacetaldehydes and N-acyl-aminopropanones. Evidence for hemithioacetal formation by a cross-saturation technique in nuclear-magnetic resonance spectroscopy. European journal of biochemistry / FEBS, , 79 (1 ) ,201-9

Cartwright, I L; Hutchinson, D W (1977. ) A simple, rapid preparation of alpha[32P]-labelled adenosine diphosphate. Nucleic acids research, , 4 (7 ) ,2507-10

Cartwright, I L; Hutchinson, D W; Armstrong, V W (1976. ) The reaction between thiols and 8-azidoadenosine derivatives. Nucleic acids research, , 3 (9 ) ,2331-9

Post Graduate Training and Education

1979-1982 Postdoctoral Fellow, Harvard University, , Cambridge, MA

1982-1985 Senior Research Associate, Washington University, , St. Louis. MO

Keywords

Toxicology,Heavy Metal,Drosophilidae,Sex Chromosome,Genetic Library,Metal Poisoning,Pharmacogenetics,Complementary Dna,Molecular Cloning,Nucleic Acid Sequence,Polymerase Chain Reaction,Transposon Insertion Element

Contact Information

Academic - Office 3005K Medical Sciences Building
231 Albert Sabin Way
Cincinnati  Ohio, 45267-0524
Phone: (513)558-5532
Fax: (513)558-8474
iain.cartwright@uc.edu