Edit Entry | Edit CV

Lionel D Lewis, MD, MA, MB-BCH

Contact Information

Professional Interests

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

Prior Clinical Pharmacology Fellows in Training have studies drugs causing autophagy in vivo, phase I drug development of an Angiopoietin II inhibitor and a hedgehog pathway inhibitor (smo-antagonist), probe drug studies of CYP450 and effects of novel anti-cancer agents on CYP450 drug metabolism

Grant Information

Co-Investigator Norris Cotton Cancer Center CCSG.
Co-Investigator SYNERGY Dartmouth CTSA (U54)

Courses Taught

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

Mentoring Information

Jennifer A. Kintner, BS, MS
Andrew P Beelen RPh, MD
Anthony Olszanski RPh, MD
Nandi J. Reddy MB. BS
Uday Dandamudi MB.BS
Shodeinde A Coker, MS, MB.BS

Biography

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 translational clinical research, clinical care and consultations, and establishing educational programs for medical students, residents and faculty.