Newcastle University

Qualifications

BSc (hons) Pharmacology 1991
MPhil 1999

Previous Positions

Research Technician 1993-1996
Junior Research associate 1996-2000

Memberships

BACR
PAMM

Research Interests

Pharmacology of novel drugs to treat cancer
Pharmacokinetics

Other Expertise

Analysis of drugs in biological material

Current Work

Evaluation of, novel drugs to inhibit DNA repair-mediated resistance to anticancer therapy, CDK inhibitors and novel nucleoside transport inhibitors to enhance antifolate efficacy.

Postgraduate Supervision

MRes student supervision 2004

Funding

Preclinical and pharmacodynamic studies with Novel DNA-PK inhibitors. N.J. Curtin (PI, 40%) A.H. Calvert (5%), BW Durkacz (10%), BT Golding (5%), RJ Griffin (5%), IR Hardcastle (5%), D.R. Newell (20%), H. Thomas (10%). KuDos Pharmaceuticals 06/02-05/06 £355,171

Preclinical evaluation of DNA-PK and ATM inhibitors. N.J. Curtin (PI, 40%) A.H. Calvert (5%), BW Durkacz (10%), BT Golding (5%), RJ Griffin (5%), IR Hardcastle (5%), D.R. Newell (20%), H. Thomas (10%). KuDos Pharmaceuticals 01/03-12/06 £413,088

Preclinical Evaluation of AT5438 D.R. Newell (PI = 50%) N.J. Curtin (25%), H. Thomas (25%). Astex Technology Ltd 05/03-05/04 £15,253

• Jarvis IWH, Meczes EL, Thomas HD, Edmondson RJ, Veal GJ, Boddy AV, Ottley CJ, Pearson DG, Tilby MJ. Therapy induced carboplatin-DNA adduct levels in human ovarian tumours in relation to assessment of adduct measurement in mouse tumours. Biochemical Pharmacology 2012, 83(1), 69-77.
• Johnson N, Li YC, Walton ZE, Cheng KA, Li DA, Rodig SJ, Moreau LA, Unitt C, Bronson RT, Thomas HD, Newell DR, D'Andrea AD, Curtin NJ, Wong KK, Shapiro GI. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nature Medicine 2011, 17(7), 875-882.
• Saravanan K, Barlow HC, Barton M, Calvert AH, Golding BT, Newell DR, Northen JS, Curtin NJ, Thomas HD, Griffin RJ. Nucleoside Transport Inhibitors: Structure-Activity Relationships for Pyrimido[5,4-d]pyrimidine Derivatives That Potentiate Pemetrexed Cytotoxicity in the Presence of alpha(1)-Acid Glycoprotein. Journal of Medicinal Chemistry 2011, 54(6), 1847-1859.
• Zaremba T, Thomas HD, Cole M, Coulthard SA, Plummer ER, Curtin NJ. Poly(ADP-ribose) polymerase-1 (PARP-1) pharmacogenetics, activity and expression analysis in cancer patients and healthy volunteers. Biochemical Journal 2011, 436(3), 671–679.
• Thomas HD, Wang LZ, Roche C, Bentley J, Cheng YZ, Hardcastle IR, Golding BT, Griffin RJ, Curtin NJ, Newell DR. Preclinical in vitro and in vivo evaluation of the potent and specific cyclin-dependent kinase 2 inhibitor NU6102 and a water soluble prodrug NU6301. European Journal of Cancer 2011, 47(13), 2052-2059.
• Ali M, Kamjoo M, Thomas HD, Kyle S, Pavlovska I, Babur M, Telfer BA, Curtin NJ, Williams KJ. The Clinically Active PARP Inhibitor AG014699 Ameliorates Cardiotoxicity but Does Not Enhance the Efficacy of Doxorubicin, despite Improving Tumor Perfusion and Radiation Response in Mice. Molecular Cancer Therapeutics 2011, 10(12), 2320-2329.
• Drew Y, Mulligan EA, Vong W, Thomas HD, Kahn S, Kyle S, Mukhopadhyay A, Los G, Hostomsky Z, Plummer ER, Edmondson RJ, Curtin NJ. Therapeutic Potential of Poly(ADP-ribose) Polymerase Inhibitor AG014699 in Human Cancers With Mutated or Methylated BRCA1 or BRCA2. Journal of the National Cancer Institute 2011, 103(4), 334-346.
• Daniel RA, Rozanska AL, Thomas HD, Mulligan EA, Drew Y, Castelbuono DJ, Hostomsky Z, Plummer ER, Boddy AV, Tweddle DA, Curtin NJ, Clifford SC. Inhibition of Poly (ADP-Ribose) Polymerase-1 Enhances Temozolomide and Topotecan Activity against Childhood Neuroblastoma. Clinical Cancer Research 2009, 15(4), 1241-1249.
• Thomas HD, Saravanan K, Wang LZ, Lin MJ, Northen JS, Barlow H, Barton M, Newell DR, Griffin RJ, Golding BT, Curtin NJ. Preclinical evaluation of a novel pyrimidopyrimidine for the prevention of nucleoside and nucleobase reversal of antifolate cytotoxicity. Molecular Cancer Therapeutics 2009, 8(7), 1828-1837.
• Darby S, Murphy T, Thomas H, Robson CN, Leung HY, Mathers ME, Gnanapragasam VJ. Similar expression to FGF (Sef) inhibits fibroblast growth factor-induced tumourigenic behaviour in prostate cancer cells and is downregulated in aggressive clinical disease. British Journal of Cancer 2009, 101(11), 1891-1899.
• Thomas HD, Calabrese CR, Batey M, Canan S, Hostomsky Z, Kyle S, Maegley K, Newell DR, Skalitzky D, Wang L, Webber SE, Curtin NJ. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Molecular Cancer Therapeutics 2007, 6(3), 945-956.
• Bryant H, Schultz N, Thomas HD, Parker K, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005, 434(7035), 913-917.
• Calabrese C, Almassy R, Barton S, Batey M, Calvert AH, Canan-Koch S, Durkacz B, Hostomsky Z, Kumpf R, Kyle S, Li J, Maegley K, Newell DR, Notarianni E, Stratford I, Skalitzky D, Thomas HD, Wang L, Webber S, William K, Curtin NJ. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. Journal of the National Cancer Institute 2004, 96(1), 56-67.
• Tikhe J, Webber S, Hostomsky Z, Maegley K, Ekkers A, Li J, Yu X, Almassy R, Kumpf R, Boritzki T, Zhang C, Calabrese C, Curtin NJ, Kyle S, Thomas HD, Wang L, Calvert AH, Golding B, Griffin RJ, Newell DR. Design, synthesis, and evaluation of 3,4-dihydro-2H-[1,4]diazepino[6,7,1- hi]indol-1-ones as inhibitors of poly(ADP-ribose) polymerase. Journal of Medicinal Chemistry 2004, 47(22), 5467-5481.
• Calabrese C, Batey M, Thomas HD, Durkacz B, Wang L, Kyle S, Skalitzky D, Li J, Zhang C, Boritzki T, Maegley K, Calvert AH, Hostomsky Z, Newell DR, Curtin NJ. Identification of potent nontoxic poly(ADP-ribose) polymerase-1 inhibitors: Chemopotentiation and pharmacological studies. Clinical Cancer Research 2003, 9(7), 2711-2718.
• Koch SSC, Thoresen LH, Tikhe JG, Maegley KA, Almassy RJ, Li JK, Yu XH, Zook SE, Kumpf RA, Zhang C, Boritzki TJ, Mansour RN, Zhang KE, Ekker A, Calabrese CR, Curtin NJ, Kyle S, Thomas HD, Wang LZ, Calvert AH, Golding BT, Griffin RJ, Newell DR, Webber SE, Hostomsky Z. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis, and X-ray cocrystal structure. Journal of Medicinal Chemistry 2002, 45(23), 4961-4974.
• Thomas HD, Porter D, Bartelink I, Nobbs J, Cole M, Elliott S, Newell DR, Calvert AH, Highley M, Boddy AV. Randomized cross-over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide. British Journal of Clinical Pharmacology 2002, 53(1), 83-91.
• Marshman, E., Taylor, G., Thomas, H., Newell, D.R., Curtin, N.J. Hypoxanthine transport in human tumour cell lines. Relationship to the inhibition of hypoxanthine rescue by dipyridamole. Biochemical Pharmacology 2001, 61(4), 477-484.
• Smith PG, Thomas HD, Barlow HC, Griffin RJ, Golding BT, Calvert AH, Newell DR, Curtin NJ. In vitro and in vivo properties of novel nucleoside transport inhibitors with improved pharmacological properties that potentiate antifolate activity. Clinical Cancer Research 2001, 7(7), 2105-2113.
• Boddy AV, Griffin MJ, Sludden J, Thomas HD, Fishwick KA, Wright J, Plummer ER, Highley MS, Calvert AH. Pharmacological study of paclitaxel duration of infusion combined with GFR-based carboplatin in the treatment of ovarian cancer. Cancer Chemotherapy and Pharmacology 2001, 48(1), 15-21.
• Thomas HD, Lind M, Ford J, Bleehen N, Calvert AH, Boddy AV. Pharmacokinetics of carboplatin administered in combination with the bradykinin agonist Cereport (RMP-7) for the treatment of brain tumours. Cancer Chemotherapy and Pharmacology 2000, 45(4), 284-290.
• Thomas HD, Boddy AV, English M, Hobson R, Imeson J, Lewis I, Morland B, Pearson ADJ, Pinkerton R, Price L, Stevens M, Newell DR. Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial. Journal of Clinical Oncology 2000, 18(21), 3614-3621.
• Calabrese CR, Thomas HD, Batey MA, Boritzki T, Zhang K, White AW, Curtin NJ, Griffin RJ, Golding BT, Hostomsky Z, Calvert AH, Newell DR. Preclinical pharmacology of novel substituted benzimidazoles - potent inhibitors of poly (ADP-ribose) polymerase. Clinical Cancer Research 1999, 5(Suppl. 1), S3839-S3839.
• Bisogno G, Cowie F, Boddy AV, Thomas HD, Dick G, Pinkerton C. High dose cyclosporin with etoposide - Toxicity and pharmacokinetic interaction in children with solid tumours. British Journal of Cancer 1998, 77(12), 2304-2309.
• Thomas HD, Boddy AV, Pearson ADJ, Pinkerton CR, Lewis I, Stevens M, Imeson J, Hobson R, Newell DR. Validation of pharmacologically-guided dosing of carboplatin in paediatric patients. British Journal of Cancer 1998,78 Suppl.1 9-9.
• Siddiqui N, Boddy AV, Thomas HD, Bailey N, Robson L, Lind M, Calvert AH. A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer. British Journal of Cancer 1997, 75(2), 287-294.
• Boddy AV, Thomas HD. RMP-7. Potential as an adjuvant to the drug treatment of brain tumours. CNS Drugs 1997. , 7(4), 257-263.
• Laohavinij S, Wedge S, Lind M, Bailey N, Humphreys A, Proctor M, Chapman F, Simmons D, Oakley A, Robson L, Gumbrell L, Taylor G, Thomas HD, Boddy AV, Newell DR, Calvert AH. A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid. Investigational New Drugs 1996, 14(3), 325-335.
• Mummaneni V, Kaul S, Igwemezie L, Newell DR, Porter D, Thomas HD, Calvert AH, Winograd B, Barbhaiya R. Bioequivalence assessment of etoposide phosphate and etoposide using pharmacodynamic and traditional pharmacokinetic parameters. Journal of Pharmacokinetics and Biopharmaceutics 1996, 24(4), 313-325.
• Porter D, Boddy AV, Thomas HD, Lind M, Newell DR, Calvert AH, Robson L, Brampton M, Abrahamsen D, Winograd B. Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: A cancer research campaign phase I/II committee study. Seminars in Oncology 1996, 23(6 supplement 13), 34-44.
• Calvert AH, Boddy AV, Bailey NP, Siddiqui N, Humphreys A, Hughs A, Robson L, Gumbrell L, Thomas H, Chapman F, Proctor M, Simmons D, Oakey A, Lind MJ, Sinha DV, Newell DR. Carboplatin in combination with paclitaxel in advanced ovarian cancer: dose determination and pharmacokinetic and pharmacodynamic interactions.. Seminars in Oncology 1995, 22(5 Suppl. 12), 91-98.