Dartmouth Medical School - Faculty Database

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Lionel D. Lewis, M.D., B.A., M.A.

Title(s):
Professor of Medicine and of Pharmacology & Toxicology

Department(s):
Medicine
Pharmacology and Toxicology

Education:
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 BCh., 1979
Univ. of Wales College of Medicine, MD 1988

Programs:
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine

Websites:
http://dms.dartmouth.edu/pharmtox/

Contact Information:

Section of Clinical Pharmacology 322 West Borwell Building Dartmouth-Hitchcock Medical Center Lebanon NH 03756
Office: Borwell 322W Phone: 603-650-8685/7811 Fax: 603-650-6841 Email: lionel.lewis@dartmouth.edu Assistant: Janet Duefield Asst. Phone: 603-650-7811 Asst. Email: janet.duefield@dartmouth.edu

Selected Publications:

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)

Mita AC, Olszanski AJ, Walovitch RC, Perez RP, MacKay K, Tuck DP, Simmons C, Hammond S, Mita MM, Beeram M, Stone AJ, Rowinsky EK, Lewis LD. Phase I and pharmacokinetic study of AI-850, a novel microparticle hydrophobic drug delivery system for paclitaxel. Clin Cancer Res. 2007 Jun 1;13(11):3293-301 (view details on MedLine)

Miller AA, Murry DJ, Owzar K, Hollis DR, Lewis LD, Kindler HL, Marshall JL, Villalona-Calero MA, Edelman MJ, Hohl RJ, Lichtman SM, Ratain MJ. Phase I and pharmacokinetic study of erlotinib for solid tumors in patients with hepatic or renal dysfunction: CALGB 60101. J Clin Oncol. 2007 Jul 20;25(21):3055-60. (view details on MedLine)

Lewis LD, Miller AA, Rosner GL, Dowell JE, Valdivieso M, Relling MV, Egorin MJ, Bies RR, Hollis DR, Levine EG, Otterson GA, Millard F, Ratain MJ; Cancer and Leukemia Group B. A comparison of the pharmacokinetics and pharmacodynamics of docetaxel between African-American and Caucasian cancer patients: CALGB 9871. Clin Cancer Res. 2007 Jun 1;13(11):3302-11. (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)

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)

Professional Interests:

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 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.

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.

Courses Taught:

DMS II Medical Pharmacology
DMS IV Medicine/Pharmacology - Clinical Pharmacology & Therapeutics

Grant Information:

Co-Investigator Norris Cotton Cancer Center CCSG.

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