Lionel D Lewis, M.D., M.A.
Professor of Medicine
Professor of Pharmacology & Toxicology
Pharmacology & Toxicology
Trinity College, Univ of Cambridge, BA 1974
Trinity College, Univ of Cambridge, MA 1978
Univ. of Wales College of Medicine, MB BCh 1977
Univ. of Cambridge MB BChir., 1979
Univ. of Wales College of Medicine, MD 1988
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Section of Clinical Pharmacology
322 West Borwell Building
Dartmouth-Hitchcock Medical Center
Lebanon NH 03756
The clinical pharmacology of antineoplastic agents, particularly the relationship between the pharmacokinetics and pharmacodynamics of these agents in early drug development and proof of principle studies.
Mechanisms of toxicity of nucleoside analogues and antineoplastic agents to the mitochondrion.
Dr. Lewis' work has focused on two areas of research at Dartmouth. He is interested in the Phase I development of antineoplastic agents and established the Phase I Oncology Group at Dartmouth where he has studied a number of anti-cancer agents in early clinical development and defined their pharmacokinetics (PK) and pharmacodynamics (PD) and the PK-PD relationships.
Dr. Lewis has an ongoing interest in drugs which are toxic to the mitochondrion e.g. anti-HIV nucleosides (AZT, ddC and ddI ). Using some of his background in this area he has developed a unique cell line derived from MOLT-4 cells and which are depleted of mtDNA and have impaired mitochondrial function compared to the wild type cell and are useful in elucidating whether the mitochondrion is a target site for xenobiotic toxicity and that the mtDNA depleted MOLT-4 cells (rh0 cells) can be converted to individualized cybrid cells containing mtDNA from humans with abnormalities in mtDNA and studied as a model system for the individual patient.
Rotations and Thesis Projects:
Clin Pharm Fellow in Training – studying effects of juices on anti-cancer drug handling, drugs causing autophagy in vivo, phase I drug development of an Angiopoietin II inhibitor and a hedgehog pathway inhibitor (smo-antagonist)
Co-Investigator Norris Cotton Cancer Center CCSG.
Co -Investigator Dartmouth Center for Cancer Nanotechnology Excellence (U54)
DMS II Medical Pharmacology
DMS IV Medicine/Pharmacology - Clinical Pharmacology & Therapeutics
Dr. Lewis received his B.A. degree from Cambridge University, England in 1974 and received his MB BCh degree from The Welsh National School of Medicine, Cardiff, Wales in 1977. He performed his internship and residency in internal medicine at the University Hospital of Wales at Cardiff and its affiliated hospitals. He then completed his internal medicine training and went on to become an Instructor in Clinical Pharmacology at Guy's Hospital, London from 1982 - 1987. During this time he completed his doctoral thesis (MD, Wales) on the clinical pharmacokinetics of ifosfamide. From 1987-89 he undertook further training and became an accredited specialist in general internal medicine, clinical pharmacology and pulmonology. From 1989-91 he completed a two-year clinical/research fellowship in clinical pharmacology at The Johns Hopkins University Hospital. He then returned to the UK to further obtain experience in Phase I drug studies at the Guys' Drug Research Unit. In 1993 he joined the faculty at Dartmouth Medical School and joined Dr. Nierenberg as the second member of the section of Clinical Pharmacology. This section is active in the areas of basic and clinical research, clinical care and consultations, and establishing educational programs for medical students, residents and faculty.
Armand R, Channon JY, Kintner J, White KA, Miselis KA, Perez RP, Lewis LD. The effects of ethidium bromide induced loss of mitochondrial DNA on mitochondrial phenotype and ultrastructure in a human leukemia T-cell line (MOLT-4 cells). Toxicol Appl Pharmacol. 2004 Apr 1;196(1):68-79. (view details on MedLine)
Perez RP, Lewis LD, Beelen AP, Olszanski AJ, Johnston N, Rhodes CH, Beaulieu B, Ernstoff MS, Eastman A. Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850). Clin Cancer Res. 2006 Dec 1;12(23):7079-85. (view details on MedLine)
Yeo T, Kintner J, Armand R, Perez R, Lewis L. Sublethal concentrations of gemcitabine (2',2'-difluorodeoxycytidine) alter mitochondrial ultrastructure and function without reducing mitochondrial DNA content in BxPC-3 human pancreatic carcinoma cells. Hum Exp Toxicol. 2007 Dec;26(12):911-21. (view details on MedLine)
Curbo S, Johansson M, Balzarini J, Lewis LD, Karlsson A. Acute cytotoxicity of arabinofuranosyl nucleoside analogs is not dependent on mitochondrial DNA. Exp Cell Res. 2009 Sep 10;315(15):2539-43. Epub 2009 May 28. (view details on MedLine)
Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, Olszanski AJ, Cohen RB. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol. 2009 Nov 1;27(31):5262-9. Epub 2009 Sep 8. (view details on MedLine)
Miller AA, Murry DJ, Owzar K, Hollis DR, Kennedy EB, Abou-Alfa G, Desai A, Hwang J, Villalona-Calero MA, Dees EC, Lewis LD, Fakih MG, Edelman MJ, Millard F, Frank RC, Hohl RJ, Ratain MJ. Phase I and pharmacokinetic study of sorafenib in patients with hepatic or renal dysfunction: CALGB 60301. J Clin Oncol. 2009 Apr 10;27(11):1800-5. Epub 2009 Mar 2. (view details on MedLine)
Goh BC, Reddy NJ, Dandamudi UB, Laubscher KH, Peckham T, Hodge JP, Suttle AB, Arumugham T, Xu Y, Xu CF, Lager J, Dar MM, Lewis LD. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther. 2010 Nov;88(5):652-9. Epub 2010 Sep 29. (view details on MedLine)
Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, Szczepiorkowski ZM, Tosteson TD, Rhodes CH, Wishart HA, Lewis LD, Ernstoff MS. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother. 2011 May;34(4):382-9. (view details on MedLine)
Shapiro GI, Frank R, Dandamudi UB, Hengelage T, Zhao L, Gazi L, Porro MG, Woo MM, Lewis LD. The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer. Cancer Chemother Pharmacol. 2012 Feb;69(2):555-62. (view details on MedLine)