Ethan Dmitrovsky, MD
Emeritus Professor of Pharmacology and Toxicology
Emeritus Professor of Medicine
Pharmacology and Toxicology
Cornell University Medical College, MD 1980
Harvard University, BS 1976
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Geisel School of Medicine at Dartmouth
Dept. of Pharmacology and Toxicology
Hanover NH 03755
Office: Remsen 523
Asst. Phone: 603-650-1667
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.
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"
Second Year Medical Pharmacology Course
Molecular Pharmacology Course
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.
Dmitrovsky E, Kuehl WM, Hollis GF, Kirsch IR, Bender TP, Segal S. Expression of a transfected human c-myc oncogene inhibits differentiation of a mouse erythroleukaemia cell line. Nature. 1986 Aug 21-27;322(6081):748-50. (view details in PubMed)
Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hitelman WN, Andreeff M, Tafuri A, Jakubowski A, Gabrilove J, Gordon M, Dmitrovsky E. Differentiation therapy of acute promyelocytic leukemia using all-trans retinoic acid. N Engl J Med 324:1385-1393, 1991. (view details in PubMed)
Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663-74 (view details in PubMed)
Early E, Moore MA, Kakizuka A, Nason-Burchenal K, Martin P, Evans RM, Dmitrovsky E. Transgenic expression of PML/RARalpha impairs myelopoiesis. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7900-4. (view details in PubMed)
Langenfeld J, Kiyokawa H, Sekula D, Boyle J, Dmitrovsky E. Post-translational regulation of cyclin D1 by retinoic acid: a chemoprevention mechanism. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12070-4. (view details in PubMed)
Kitareewan S, Pitha-Rowe I, Sekula D, Lowrey CH, Nemeth MJ, Gollub TR, Freemantle SJ, Dmitrovsky E. UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3806-11. Epub 2002 Mar 12. (view details in PubMed)
Kitareewan S, Roebuck BD, Demidenko E, Sloboda RD, Dmitrovsky E. Lysosomes and trivalent arsenic treatment in acute promyelocytic leukemia. J Natl Cancer Inst. 2007 Jan 3;99(1):41-52. (view details in PubMed)
Ma Y, Fiering S, Black C, Liu X, Yuan Z, Memoli VA, Robbins DJ, Bentley HA, Tsongalis GJ, Demidenko E, Freemantle SJ, Dmitrovsky E. Transgenic cyclin E triggers dysplasia and multiple pulmonary adenocarcinomas. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4089-94. Epub 2007 Feb 27. (view details in PubMed)
Galimberti F, Thompson SL, Liu X, Li H, Memoli V, Green SR, DiRenzo J, Greninger P, Sharma SV, Settleman J, Compton DA, Dmitrovsky E. Targeting the cyclin E-Cdk-2 complex represses lung cancer growth by triggering anaphase catastrophe. Clin Cancer Res. 2010 Jan 1;16(1):109-20. Epub 2009 Dec 22. (view details in PubMed)
Liu X, Sempere LF, Ouyang H, Memoli VA, Andrew AS, Luo Y, Demidenko E, Korc M, Shi W, Preis M, Dragnev KH, Li H, Direnzo J, Bak M, Freemantle SJ, Kauppinen S, Dmitrovsky E. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J Clin Invest. 2010 Apr 1;120(4):1298-309. doi: 10.1172/JCI39566. Epub 2010 Mar 8. (view details in PubMed)