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Ethan Dmitrovsky, M.D.

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Dr. Dmitrovsky conducts bench to bedside research, known as translational research, in studies of vitamin A derivatives known as retinoids and their roles in tumor cell differentiation therapy or chemoprevention.

Dr. Dmitrovsky completed his undergraduate studies at Harvard College in 1976, majoring in Biochemistry. He received his medical degree in 1980 from Cornell University Medical College. In 1983, he completed a residency in internal medicine at New York Hospital-Memorial Sloan-Kettering Cancer Center. In 1987, he completed training in medical oncology and in molecular oncology at the National Cancer Institute in Bethesda. Dr. Dmitrovsky had been on the faculty at Memorial Sloan-Kettering Cancer Center since 1987, holding the rank of Associate Member in the Department of Medicine and in the Molecular Pharmacology and Therapeutics Program. At that Center, Dr. Dmitrovsky headed the Laboratory of Molecular Medicine while directing the NIH K12 funded Clinical and Molecular Cancer Research Training Program. In 1998, Dr. Dmitrovsky joined the faculty at Dartmouth as the Andrew G. Wallace Professor of Pharmacology and Toxicology and of Medicine and assumed the Chair of Pharmacology and Toxicology. For the 2002-2003 academic year, Dr. Dmitrovsky was appointed Acting Dean, Dartmouth Medical School, and he now serves as Senior Advisor to the President of Dartmouth College for Science and Technology. In 2008, Dr. Dmitrovsky was named as an American Cancer Society Clinical Research Professor.

This laboratory explores the role of natural or synthetic derivatives of vitamin A – known as the retinoids – in tumor cell differentiation or chemoprevention. The pharmacological approach taken is known as “bench to bedside” or translational research. This research team focuses on the role of nuclear retinoid receptors and their activated target genes in triggering differentiation therapy or chemoprevention. In these studies, the role of classical retinoid receptors and non-classical retinoid receptors that engage the retinoic acid receptors (RAR) and retinoid X receptors (RXR), respectively, are studied. Models examined include retinoid-mediated germ cell tumor and acute promyelocytic leukemia differentiation and retinoid-dependent chemoprevention in the lung. This research team helped uncover the link that exists between successful differentiation therapy in acute promyelocytic leukemia and expression of the rearranged retinoid receptor, PML/RARá. This was accomplished by use of molecular genetic studies including transcriptional activation experiments and “gain of function” transgenic studies, “loss of function” studies to target PML/RARá, and gene profiling experiments to uncover retinoid target genes. This team found new retinoid chemopreventative pathways involving the proteasome-dependent degradation of G1 cyclins and transcriptional repression of the epidermal growth factor receptor. This is hypothesized to cause G1 arrest and thereby permit repair of genomic DNA damage. Proof of principle trials are now underway at Dartmouth to translate these findings from the laboratory to the clinic, with encouraging results.

Courses Taught:

Second Year Medical Pharmacology Course
Molecular Pharmacology Course

Grant Information:

NIH R01-CA111422 "Cyclin D as a Retinoid Molecular Target"

NIH R01-CA87546 "Retinoid Cancer Prevention Mechanisms"

NIH RO1-CA62275 "The Retinoic Acid Paradox and Promyelocytic Leukemia"

NIH RO3-CA130102 "MicroRNAs and Lung Carcinogenesis"
NIH RO3-CA1321665 "The Hedgehog Pathway and Lung Cancer Prevention"
American Cancer Society Clinical Research Professorship: “Bidirectional Translational Research for Lung Cancer”
Samuel Waxman Cancer Research Foundation: "Rexinoid Therapy for Lung Cancer Prevention"
Merck: “Vorinostat for Lung Cancer”
Cyclacel Ltd: “Proof of Principle Seliciclib Studies for Transgenic Lung Cancer”