Donald M. Miller, M.D., Ph. D.
Director, James Graham Brown Cancer Center, Professor of Medicine
Clinical Translational Research Building
University of Louisville
505 Hancock St.
Louisville, KY 40202, USA
Phone Number: 502-562-4585 (Office)
Fax Number: 502-562-4368
- Professor of Medicine, Director of Medical Oncology
- James Graham Brown Chair of Oncology
- Associate Vice President of Health Affairs
- Professor of Biochemistry & Molecular Genetics
- B. S., Chemistry and Biology, Florida State University, 1967
- Ph. D., Biochemistry, Duke University, Durham, N.C., 1973
- M. D., Duke University, Durham, N.C., 1973
- Internship and Residency, Internal Medicine, Peter Bent Brigham, Boston, MA, 1973-1975
- Clinical Associate, NHLBI, National Institutes of Health, Bethesda, MD, 1975-1978
- Senior Staff Associate, NCI, National Institutes of Health, Bethesda, MD 1978-1979
- Board Certified, Internal Medicine, 1979
Dr. Miller's laboratory has a longstanding interest in modulation of gene expression as a potential anticancer therapy. During the past decade, his group has characterized the growth inhibitory activity of a set of four-stranded quadruplex-forming oligonucleotides that bind to nucleolin. These unique oligonucleotides inhibit growth of a variety of cancer cell types, but appear to have no effect on nontransformed cells. One of these oligonucleotides (AS1411) has been studied in a Phase I clinical trial at the Brown Cancer Center and has been shown to have significant clinical activity, with no toxicity. AS1411 has been tested in more than 250 patients in multicenter Phase II trials in acute myelogenous leukemia and renal cell carcinoma demonstrating significant clinical activity and almost no toxicity.
His group is currently characterizing the growth inhibitory activity of naturally occurring, genomic quadruplex-forming sequences which selectively inhibit proliferation of transformed cells. They have shown that oligonucleotides encoding the quadruplex-forming silencer sequence in the c-Myc promoter stabilize the quadruplex structure of the genomic DNA via strand invasion, inhibiting c-Myc transcription and expression resulting in inhibition of cell proliferation. They have also shown, in collaboration with Dr. John Trent and Dr. Brad Chaires, that the common mutations in the hTERT promoter, which occur in >80% of melanoma and glioblastoma patients, result in destabilization of the quadruplex DNA structure formed by this sequence. They have shown that strand-invading oligonucleotides encoding this sequence reverse this abnormality and result in downregulation of telomerase expression. Oligonucleotides targeting the c-Myc and hTERT promoter are now in preclinical testing.
- Miller, D.M., Turner, P., Nienhuis, A.W., Axelrod, D.E., Gopalakrishanan, T.K.: Active conformation of the globin genes in uninduced and induced mouse erythroleukemia cells. Cell 14:511-522, 1978.
- Koller, C., Miller, D.: Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea. NEJM 315:1433-1438, 1986.
- Bates PJ, Laber DA, Miller DM, Thomas SD, Trent JO; Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol. 2009 Jun; 86 (3):151-164.
- Lane AN, Fan TW, Higashi RM, Tan J, Bousamra M, Miller DM; Prospects for clinical cancer metabolomics using stable isotope tracers. Exp. Mol. Pathol. 2009 Jun; 86 (3):165-173.
- Fan, TW, Lane, AN, Higashi, RM, Farag, MA, Gao, H, Bousamra, M, and Miller, DM: Altered Regulation of Metabolic Pathways in Human Lung Cancer Discerned by (13)C Stable Isotope-Resolved Metabolomics (SIRM). Molecular Cancer, 2009 Jun 26;8:41.
- Lane AN, Fan TW, Bousamra M, Higashi RM, Yan J, Miller DM. Stable Isotope-Resolved Metabolomics (SIRM) in Cancer Research with Clinical Application to Non-Small Cell Lung Cancer. OMICS. 2011 March:15(3):173-82.
- Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG: Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 2011 Oct; 19(10):1769-79. doi: 10.1038/mt.2011.164. Epub 2011 Sep 13.
- Sedoris KC, Thomas SD, Clarkson CR, Muench D, Islam A, Singh R, Miller DM: Genomic c-Myc Quarduplex DNA Selectively Kills Leukemia. Mol Cancer Ther. 2012 Jan;11(1):66-76. [Epub 2011 Nov. 14]
- Miller DM, Thomas SD, Islam A, Muench D, Sedoris K.: c-Myc and Cancer Metabolism. Clin Cancer Res. 2012 Oct 15;18(20):5546-53. doi: 10.1158/1078-0432.CCR-12-0977.
- Islam MA, Thomas SD, Slone S, Alatassi H, Miller DM: Tumor-associated primo vascular system is derived from xenograft, not host. Exp Mol Pathol. 2012 Sep 19. doi:pii: S0014-4800(12)00126-8. 10.1016/j.yexmp.2012.09.004.
- Wang Q, Zhuang X, Mu J, Deng ZB, Jiang H, Xiang X, Wang B, Yan J, Miller D, Zhang HG.: Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids. Nat Commun. 2013;4:1867. doi: 10.1038/ncomms2886.
- Islam, A, Thomas, S, Miller, DM: Pu-27 G-quadruplex induces extensive DNA damage in both telomeric and non-telomeric regions of DNA. J. Biol. Chem, 2014 Mar 21;289(12):8521-31. doi: 10.1074/jbc.M113.505073. Epub 2014 Jan 24.
- Chaires, JB, Trent, JO, Gray, RD, Dean, WL, Busgaglia, R, Thomas, SD, Miller, DM: Common hTERT Promoter Mutations Cause Quadruplex DNA Instability and Constitutive Overexpression of hTERT PLoS One. 2014 Dec 19;9(12):e115580. doi: 10.1371/journal.pone.0115580. eCollection 2014.
- Lane AN, Fan TW, Higashi RM, Tan J, Bousamra M, Miller DM.: Clinical Cancer Metabolomics; Analysis of Cancer Cell Metabolism in Human Patients; J Clin Invest. 2015 Feb;125(2):687-98. doi: 10.1172/JCI72873. Epub 2015 Jan 20.
- Basu, P., Jenson, AB, Majhi, T., Choudhury, P., Mandal, R., Singh, P., Banerjee, D, Biswas, J., Rai, S., Ghim, S., Miller, D.: Randomized Phase II trial to compare Interferon-alpha plus retinoic acid with cisplatin alone as adjunct to radiation therapy in stage III carcinoma of cervix. International Journal of Radiation Oncology, Biology, Physics94(1) 102–110, 2016
- Zhang HG, Cao P, Teng Y, Hu X, Wang O, Yeri A, Zhuang X, Samykutty A, Mu J, Bin Deng Z, Zhang L, Mobley J, Yan J, Keuren-Jensen K, Miller D: Isolation, identification, and characterization of novel nanovesicles; Oncotarget, published online 5/16.
- Zahin, M; Joh, J; Khanal, S.; Husk, A.; Mason, H.; Warzecha, H.; Ghim, S-J; Miller, D.M.; Matoba, N.; Jenson, A.B.; Scalable Production of HPV16 L1 Protein and VLPS from Tobacco Leaves; PLoS One. 2016 Aug 12;11(8):e0160995. doi: 10.1371/journal.pone.0160995. eCollection 2016. PMID:27518899
- Rezzoug, F., Thomas, S.D., Miller, D.M.; Discovery of a family of genomic sequences which interact specifically with the c-MYC promoter to regulate c-MYC expression. Plos One, In press.
Recent Patents & Licenses:
- US Patent 2015/018776 Compositions and Methods for Treating Cancer, Inhibiting Cell Proliferation and Inhibiting Cell Growth. (Filed March 4, 2015)
- U.S. Provisional Patent Application: 61/900,570, Family of G-rich Genomic Sequences Interact Specifically with the Pu27 Silencer Element of the c-Myc Promoter. Filed: November 6, 2013.
- US Patent 8,586,717, Method for the Diagnosis and Prognosis of Malignant Diseases. Issued November 19, 2013U.S. Patent 8,410,070, Compositions and methods for treating cancer, inhibiting proliferation, and inducing cell death. Issued April 2, 2013.
- US Patent U.S.8,029,784, Method for the Diagnosis and Prognosis of Malignant Diseases. Issued October 4, 2011.
- US Patent 7,960,540, Antiproliferative activity of G-rich oligonucleotides and method of using same to bind to nucleolin . Issued June 14, 2011
- U.S. Patent 7,541,150 Methods for the diagnosis of cancer by determining the neoplastic status of a cell by probing the cell plasma membrane for the presence of nucleolin are provided, as are kits to carry out such tests. Issued June 2, 2009.
- U.S. Patent 7,357,928 Methods for the treatment of tumors and cancer by exploiting the surface expression of the usually nuclear-localized protein, nucleolin. Issued April 15, 2008.
- U.S. Patent 7,314,926 Antiproliferative activity of g-rich oligonucleotides and method of using same to bind to nucleolin. Issued January 1, 2008.
Recent Awards & Honors:
- Recipient, Founders Medal, Southern Society of Clinical Investigation
- Recipient, Kentucky HERO Award, Louisville Science Museum
- Recipient, University Distinguished Medal of Scholarly Accomplishment, University of Louisville
- Recipient, Distinguished Faculty Award for Service in the community, commonwealth and region, University of Louisville