Dr. Michael Carty

• Career history
  1982 B.Sc. (Biochemistry, Hons. 1st class).
  1986 Ph.D. Department of Biochemistry, University College, Galway.
  1986-1990 Fogarty Fellowship, National Institutes of Health, Bethesda, MD, U.S.A.
  1991-1994 Research Associate, Department of Environmental, Health, University of Cincinnati Medical Center, Cincinnati, OH.
  1995-1999 Research Assistant Professor, and Head, Molecular & Cellular Biology Core laboratory, Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH.
  2000-present College Lecturer/Senior Lecturer, and Head, DNA Damage Response laboratory, Biochemistry, School of Natural Sciences, National University of Ireland, Galway, Ireland; Investigator, Centre for Chromosomal Biology, NUI, Galway.
  
  
• Research Interests
  
  Our research interests include the molecular basis of the response of human cells to DNA damaging agents, such as the carcinogen ultraviolet light, and platinum-based chemotherapeutic agents including cisplatin and oxaliplatin.
  
  To elucidate the effects of damage on DNA replication arrest, and the activation of downstream damage signaling pathways, we have developed unique human cell lines to investigate the role of human POLH gene products, DNA polymerase eta, in the response to DNA damaging agents, and used small molecule protein kinase inhibitors to probe the role of PIKK-dependent protein phosphorylation in this response, focusing on phosphorylation of replication protein A (RPA). The status of the POLH gene has also been characterised in a cohort of skin cancer patients.
  
  Ongoing research areas include the characterisation of DNA damage response pathways in human mesenchymal stem cells (hMSCs), in collaboration with the Prof. Frank Barry, Regenerative Medicine Institute, NUI, Galway, and characterisation of responses to novel derivatives of the anti-cancer drug mitomycin C in normal and Fanconi anemia cell lines (in collaboration with Dr. Fawaz Aldabbagh, School of Chemistry, NUI, Galway).
  
  We are also investigating the cellular responses to long-wavelength UVA radiation. Exposure of mammalian cells to enviornmental agents such as UV radiation is a known carcinogen. However the effects of long-wavelength UVA radiation on the DNA damage response is not well understood. The effects of UVA-radiation effects on key DDR pathways in human cells, including melanocytes, are being characterised, using flow cytometry, immunofluorescence and gene expression analysis.
  
  
• Researchers –
  Postgraduate students
  Kathleen Gallagher, B.Sc. 
  Sangamitra Villalan, B.Sc.
  Ania Sokol, M.Sc.
  Sarah Conmy B.Sc
  
  Post-doctoral researchers
  Severine Cruet-Hennequart, Ph.D.
  
  
• Publications
  
  

  1. Cuffe S, Dowling CM, Claffey J, Pampillón C, Hogan M, Fitzpatrick JM, Carty MP, Tacke M, Watson RW. Effects of titanocene dichloride derivatives on prostate cancer cells, specifically DNA damage-induced apoptosis. Prostate (2011) 71(2):111-24. 
  
  2 .O'Meara E, Cruet-Hennequart S, Carty MP. Analysis of protein phosphorylation in cisplatin-treated human cells following annexin V-based separation and multi-antibody screening. Cancer Genomics Proteomics (2010) 7(5):279-86 
  
  3. Moriarty E, Carr M, Bonham S, Carty MP, Aldabbagh F. Synthesis and toxicity towards normal and cancer cell lines of benzimidazolequinones containing fused aromatic rings and 2-aromatic ring substituents. Eur J Med Chem. (2010) 45(9):3762-9. 
  
  4. Fagan V, Bonham S, Carty MP, Aldabbagh F. One-pot double intramolecular homolytic aromatic substitution routes to dialicyclic ring fused imidazobenzimidazolequinones and preliminary analysis of anticancer activity. Org Biomol Chem. (2010) 8(14):3149-56. 
  
  5. Cruet-Hennequart S, Prendergast AM, Barry FP, Carty MP. Human mesenchymal stem cells (hMSCs) as targets of DNA damaging agents in cancer therapy. Curr Cancer Drug Targets (2010) 10(4):411-21. Review 
  
  6. Grzywa R, Sokol AM, Sieñczyk M, Radziszewicz M, Koœcio³ek B, Carty MP, Oleksyszyn J. New aromatic monoesters of alpha-aminoaralkylphosphonic acids as inhibitors of aminopeptidase N/CD13. Bioorg Med Chem. (2010) 18(8):2930-6. 
  
  7. Fahey K, O'Donovan L, Carr M, Carty MP, Aldabbagh F. The influence of the aziridinyl substituent of benzimidazoles and benzimidazolequinones on toxicity towards normal and Fanconi anaemia cells. Eur J Med Chem. (2010) 45(5):1873-9.
   
  8. Cruet-Hennequart S, Gallagher K, Sokol AM, Villalan S, Prendergast AM, Carty MP. DNA polymerase eta, a key protein in translesion synthesis in human cells. Subcell Biochem. (2010) 50:189-209. Review. 
  
  9. Cruet-Hennequart S, Villalan S, Kaczmarczyk A, O'Meara E, Sokol AM, Carty MP. Characterization of the effects of cisplatin and carboplatin on cell cycle progression and DNA damage response activation in DNA polymerase eta-deficient human cells. Cell Cycle (2009) 8(18):3039-50. 
  
  10. Stephan H, Concannon C, Kremmer E, Carty MP, Nasheuer HP. Ionizing radiation-dependent and independent phosphorylation of the 32-kDa subunit of replication protein A during mitosis. Nucleic Acids Res. (2009) 37(18):6028-41. 
  
  11. O'Donovan L, Carty MP, Aldabbagh F. First synthesis of N-[(aziridin-2-yl)methyl]benzimidazolequinone and analysis of toxicity towards normal and Fanconi anemia cells. Chem Commun (Camb). (2008) 43:5592-4. 
  
  12.  Cruet-Hennequart S, Glynn MT, Murillo LS, Coyne S, Carty MP. Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin. DNA Repair (Amst). (2008) 7(4):582-96.
  
  13. Hehir, S., O’Donovan, L., Carty, M.P. and Aldabbagh, F.  Synthesis of dimethyl substituted benzimidazoles containing cyclopropane fused onto eight membered [1,2-a]alicyclic rings and influence of methyl group substituents on cytotoxicity of benzimidazolequinones. Tetrahedron 64:4196-4203 (2008).
  
  14.  Flanagan AM, Rafferty G, O'Neill A, Rynne L, Kelly J, McCann J, Carty MP. The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin. Int J Mol Med. (2007) 19(4):589-96. 
  
  15. Lynch M, Hehir S, Kavanagh P, Leech D, O'Shaughnessy J, Carty MP, Aldabbagh F. Synthesis by radical cyclization and cytotoxicity of highly potent bioreductive alicyclic ring fused [1,2-a]benzimidazolequinones. Chemistry (2007) 13(11):3218-26. 
  
  16. Cruet-Hennequart S, Coyne S, Glynn MT, Oakley GG, Carty MP. UV-induced RPA phosphorylation is increased in the absence of DNA polymerase eta and requires DNA-PK. DNA Repair (Amst). (2006) 5(4):491-504. 
   

• Lectures/ courses
  Lecture courses to 1st, 2nd, 3rd and 4th year to Biochemistry, Biotechnology, Biomedical Science; 1st Medical, 2nd Medical, at NUI, Galway.
  
  1st Medicine: Introduction to Biochemistry.
  
  2nd Medicine: Molecular medicine:DNA Repair and Cancer.
  
  1st Biomedical Science: Topic 'Advances in Molecular Medicine'
  
  2nd year Biochemistry/Biomedical Science/Biotechnology
  Title: Nitrogen metabolism
  This course covers an overview of degradation of amino acids; Essential and non-essential amino acids; amino acids as precursors of other biological compounds e.g.TCA cycle intermediates, neurotransmitters and hormones; transamination and deamination reactions; the urea cycle; purine and pyrimidine biosynthesis; breakdown of purines; heme synthesis and breakdown.
  
  3rd Biochemistry/Biomedical Science/Biotechnology
  Title: Cancer: Loss of regulation and the control of cell division
  This course includes an Introduction to cancer terminology; imbalance between cell division and cell death; Mechanisms of regulation in the cell cycle: checkpoints. Mutations in genes encoding key cell cycle control proteins. Oncogenes and tumour suppressor genes: definitions and examples of their roles in cancer development and progression.
  
  4th Biochemistry/Biomedical Science/Biotechnology
  Title: Genome Stability
  Topics covered include Genome stability, DNA damage and mutations; DNA repair pathways; novel DNA polymerases; Repair defects and cancer predisposition: xeroderma pigmentosum (XP), ataxia telangiectasia (AT); mismatch repair and colon cancer.
  

• Disclaimer
• Privacy
• Copyright
• Accessibility