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Ethan Dmitrovsky, MD

Contact Information

Professional Interests

Dr. Ethan Dmitrovsky is a physician-scientist and practicing oncologist. He studies vitamin A derivatives (retinoids) in cancer therapy and prevention and conducts bench to bedside or translational research. His team helped establish retinoid differentiation therapy for acute promyelocytic leukemia and developed the reverse transcription polymerase chain reaction assay used to diagnose this leukemia and monitor minimal residual disease. His team also found a novel protein destruction mechanism that caused degradation of the dominant-negative translocation product found in this leukemia, PML/RAR-alpha. A novel mechanism responsible for diverse retinoid clinical effects was found to occur through a common pathway that caused G1 arrest. This permitted a differentiation program to proceed or genomic damage to be repaired, depending on the cell context. This mechanism activated proteasomal degradation of G1 cyclins, causing G1 arrest. His team engineered transgenic mice that targeted expression in the lung of wild-type or degradation-resistant cyclin E proteins. These mice recapitulated frequent features of human lung carcinogenesis, especially when degradation-resistant cyclin E species were present. Transplantable transgenic lung cancer models were developed from these mice. These models are useful to study lung cancer biology and to find ways to combat lung cancer, by treating or preventing this most common cause of cancer death for men and women in our society. The team has launched and completed proof of principle clinical trials and discovered that the same degradation pathways identified in the laboratory were activated in cancers of patients.

Rotations and Thesis Projects

1. Identification of novel retinoic acid target genes as targets for cancer therapy and prevention.
2. Induced cyclin proteolysis as a target for cancer therapy and prevention.
3. MicroRNAs as new targets for lung cancer therapy and prevention.
4. Retinoids as regulators of hedgehog signaling.

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 R01-AT005382 (Co-Investigator) "Vitamin A and Acquired Immune Privilege"
American Cancer Society Clinical Research Professorship: "Bidirectional Translational Research for Lung Cancer"
Samuel Waxman Cancer Research Foundation: "Rexinoid Therapy for Lung Cancer Prevention"

Courses Taught

Second Year Medical Pharmacology Course
Molecular Pharmacology Course

Biography

Dr. Dmitrovsky graduated from Harvard College and Cornell University Medical College. He completed an internal medicine residency at New York Hospital-Memorial Sloan-Kettering Cancer Center and a fellowship at the National Cancer Institute. Dr. Dmitrovsky was on the faculty at Memorial Sloan-Kettering Cancer Center for more than a decade before joining Dartmouth as the Andrew G. Wallace Professor and chair of the Pharmacology department. He served a decade as chair of the Pharmacology department and completed a term as Acting Dean of the Dartmouth Medical School. Dr. Dmitrovsky serves on several editorial boards including Cancer Research, Clinical Cancer Research, Molecular Cancer Therapeutics, Cancer Prevention Research, and the Journal of the National Cancer Institute. He is Associate Director of the Samuel Waxman Cancer Research Foundation and serves on scientific advisory boards, including the Board of Scientific Counselors of the National Cancer Institute and the Lance Armstrong Foundation. He testified before the President's Cancer Panel about overcoming barriers to translational research and now serves as chair of the Board of Scientific Counselors of the National Cancer Institute for Clinical Sciences and Epidemiology. Dr. Dmitrovsky is an American Cancer Society Clinical Research Professor and conducts bidirectional translational research.