Faculty Profile
Dr. Howell Stephen Howell, M.D.
Professor of Medicine
Division of Hematology-Oncology
Associate Director for Clinical Research
Moores UCSD Cancer Center
Office Address:
Division of Hematology-Oncology
University of California
Moores UCSD Cancer Center
3855 Health Sciences Drive, MC-0819
La Jolla, CA 92093
showell@ucsd.edu
Office: (858) 822-1110
FAX: (858) 822-1111
| Education/Training | Research Interests | Publications | Laboratory |
Education and Training
| BA | University of Chicago | 1966 |
| MD | Harvard Medical School | 1970 |
| Intern/Resident | Massachusetts General Hospital | 1970-1972 |
| Research Associate | Laboratory of Cell Biology, NCI | 1972-1974 |
| Resident | University of California Hospitals | 1974-1975 |
| Fellow | Oncology, Dana Farber Cancer Institute | 1975-1977 |
Research Interests
Dr. Stephen Howell’s work focuses on the development of novel drugs and drug delivery systems for the treatment of cancer, and on the molecular and genetic mechanisms underlying the development of drug resistance. He conducted much of the early pharmacokinetic information and clinical trials work on intraperitoneal chemotherapy for the treatment of ovarian cancer. His laboratory has contributed importantly to the current understanding of how the platinum-containing drugs enter, traffic through and exit from ovarian cancer cells, and how much cells become resistant to these drugs.
Publications
Rich JR, Gerberich JL, Nowotnik DP, Howell SB. Preclinical efficacy and pharmacokinetics of AP5346, a novel DACH-platinum tumor-targeting drug delivery system. Clin Cancer Res, 12:2248-2254, 2006.
Lin X, Howell SB. DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance. Mol Cancer Therapeut, 5:1239-1247, 2006.
Holzer AK, Varki NM, Le QT, Naredi P, Gibson MA, Howell, SB. Expression of the human coper influx transporter 1 in normal and malignant human tissues. J Histochem Cytochem, 54:1041-1049, 2006.
Holzer AK, Manorek GH, Howell SB. The contribution of the major copper influx transporter CTR1 to the cellular accumulation of cisplatin, carboplatin and oxaliplatin. Mol Pharmacol, 70:1390-1394, 2006.
Holzer AK, Howell SB. The internalization and degradation of human copper transporter 1 following cisplatin exposure. Cancer Res, 66:10944-10952, 2006.
Samimi G, Kishimoto S, Manorek G, Breaux JK, Howell SB. Novel mechanisms of platinum drug resistance identified in cells selected for resistance to JM118 the active metabolite of satraplatin. Cancer Chemo Pharm, 59:301-312, 2007.
Kong SD, Luong A, Manorek G, Howell SB, Yang J. Acidic hydrolysis of n-ethoxybenzylimidazoles (NEBIs): potential applications as pH-sensitive linkers for drug delivery. Bioconjug chem., 18:293-296, 2007.
Campone M, Rademaker-Lakhai JM, Bennouna J, Howell SB, Nowotnik DP, Beijnen JH, Schellens JHM. Phase I and pharmacokinetic trials of AP5346, a Dach-platinum-polymer conjugate, administered weekly for three out of every four weeks to advanced solid tumor patients. Cancer Chemother Pharmacol, 60:523-533, 2007.
Lee S, Howell SB, Opella SJ. NMR and mutagenesis of human Copper Transporter 1 (hCtr1) show that Cys-189 is required for correct folding and dimerization. Biochem Biophys Acta, 1768(12):3127-34. Epub Sept 2007.
Safaei R, Larson BJ, Otani S, Rasmussen ML, Howell SB. Transport of cisplatin by the copper efflux transporter ATP7B. Mol Pharmacol, 73:461-468, 2008.
Kowalski D, Pendyala L, Daignan-Fornier B, Howell, SB, Huang RY. Disregulation of purine nucleotide biosynthesis pathways modulates cisplatin cytotoxicity in saccharomyces cerevisiae. Mol Pharmacol, 2008 July 8.
