Dr Lonnie Swift
One of the functions of the human genome is to pass on the genetic material to the daughter cell. The integrity of this genome is paramount to the stability of the organism. There are many diseases that result from a lack of genomic stability, such as cancer. There are also many different DNA repair mechanisms that protect a cell’s genome against the thousands of different genotoxic insults it encounters every day. The importance of genome integrity, or maintaining the correct DNA sequence, can be highlighted by the fact that the DNA of a cell is the only macromolecule that is repaired, all other cellular macromolecules can be degraded and re-made if they are damaged.
My work focuses on understanding the mechanisms that protect the genome from potentially detrimental damage, namely the DNA repair pathways. Many proteins play vital roles in repairing DNA damage, such as proteins with helicase activity, polymerase activity and nuclease activity. Most of my research focuses on the nucleases involved in DNA repair. These proteins play the important role of removing damaged DNA bases, or sections of DNA that must be removed for further repair to take place.
Understanding the DNA repair processes will enable development of drugs that can synergise with pre-existing mutations in diseased cells. Some examples of targeting this synergy already exist in the clinic, but fully understanding all mechanistic processes of DNA repair will aid the understanding of disease pathogenesis as well as aiding future drug development.
I teach undergraduates reading Biochemistry and Medicine. My teaching focus is on molecular cellular biochemistry and medical genetics in the first year. I also teach genetics and molecular biology (with a focus on replication, transcription and DNA repair) to second and third year students.
- SB Hatch*, LP Swift*, S Caporali, R Carter, EJ Hill, TP MacGregor, S D’Atri, PJ McHugh, RA Sharma (2014) XPF protein levels determine sensitivity of malignant melanoma cells to oxiplatin chemotherapy: Suitability as a biomarker for patient selection. International Journal of Cancer 134: 1495-503
(*equal first authors).
- RA Forrest, LP Swift, BJ Evison, A Rephaeli, A Nudelman, DR Phillips, SM Cutts (2013) The hydroxyl epimer of doxorubicin controls the rate of formation of cytotoxic anthracycline-DNA adducts. Cancer Chemotherapy and Pharmacology, 71(3):809-16
- RA Forrest, LP Swift, A Rephaeli, A Nudelman, K Kimura, DR Phillips, SM Cutts (2012) Activation of DNA damage response pathways as a consequence of anthracycline-DNA adduct formation. Biochemical Pharmacology, 83:1602-1612.
- AT Wang, B Sengerova, E Cattell, T Inagawa, JM Hartley, K Kiakos, NA Burgess-Brown, LP Swift, JH Enzlin, CJ Schofield, O Gileadi, JA Hartley, PJ McHugh (2011) Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair. Genes & Development, 25(17), 1859-70
- DR Phillips, LP Swift, KE Coldwell, DMS Spencer, R Bilardi, BJ Evison, O Mansour, A Nudelman, A Rephaeli, TH Koch and SM Cutts (2010) Drug-DNA Adducts formed by formaldehyde activation of anthracyclines and related anti-cancer agents. In: DNA Adducts: formation, detection and mutagenesis, Eds E Alvarez, R Cunha. Nova Publishing.
- K Kimura, DMS Spencer, R Bilardi, LP Swift, AJ Box, RTC Brownlee, SM Cutts and DR Phillips (2010) Barminomycin, a model for the development of new anthracyclines. Anti-cancer agents in Medicinal Chemistry [Review], 10:70-77.
- I Levovich, A Nudelman, G Berkovitch, LP Swift, SM Cutts, DR Phillips and A Rephaeli (2008) Formaldehyde-releasing prodrugs specifically affect cancer cells by a depletion of intracellular glutathione and augmentation of reactive oxygen species. Cancer Chemotherapy and Pharmacology, 62: 471-482.
- LP Swift, A Nudelman, I Levovich, A Rephaeli, SM Cutts and DR Phillips (2008) The cardio-protecting agent and topoisomerase II catalytic inhibitor sobuzoxane enhances doxorubicin-DNA adduct mediated cytotoxicity. Cancer Chemotherapy and Pharmacology, 61:739-49.
- SM Cutts*, LP Swift*, V. Pillay, R Forrest, A Nudelman, A Rephaeli and DR Phillips (2007). Activation of clinically used anthracyclines by the formaldehyde-releasing prodrug Pivaloyloxymethyl butyrate. Molecular Cancer Therapeutics, 6:1450-9.
(*equal first authors)
- LP Swift, A Rephaeli, A Nudelman, DR Phillips and SM Cutts (2006). Doxorubicin-DNA adducts induce a non-topoisomerase II mediated form of cell death. Cancer Research, 66: 4863-71.
- SM Cutts, LP Swift, A Rephaeli, A Nudelman and DR Phillips (2005). Recent advances in understanding and exploiting the activation of anthracyclines by formaldehyde. Current Medicinal Chemistry - Anti-Cancer Agents. 5:431-47.
- SM Cutts, LP Swift, A Rephaeli, A Nudelman and DR Phillips (2003). Sequence specificity of Adriamycin-DNA adducts in human tumor cells. Molecular Cancer Therapeutics, 2:661-70.
- LP Swift, SM Cutts, A Rephaeli, A Nudelman and DR Phillips (2003). Activation of Adriamycin by the pH dependent formaldehyde-releasing prodrug hexamethylenetetramine. Molecular Cancer Therapeutics, 2:189-98.
- SM Cutts, BS Parker, LP Swift, KI Kimura and DR Phillips (2000). Structural requirements for the formation of anthracycline-DNA adducts. Anticancer Drug Design, 15:373-86.