Donald M Miller, M.D., Ph.D.

Education:

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

Curriculum Vitae

Current Positions:

Professor of Medicine, Director of Medical Oncology
James Graham Brown Chair of Oncology
Director, James Graham Brown Cancer Center
Associate Vice President of Health Affairs

Clinical Focus and Research:

Dr. Miller has been involved  in the treatment of patients with malignant melanoma for more than three decades.  He has been involved in quite a number of clinical trials during that time and has had a particular interest in novel adjuvant treatments for patients at high risk for recurrence.  He works with Dr. Chesney and Dr. McMasters in the Melanoma and Skin Cancer Multidisciplinary Clinic at the Brown Cancer Center.

Dr. Miller’s research interests include development of novel oligonucleotide-based therapies.  With Dr. Bates and Dr. Trent, he developed AS1411, a four stranded DNA molecule which was the first DNA aptamer tested in cancer patients.  AS1411 demonstrated significant clinical activity and very little toxicity.  His group is now developing gene-targeted oligonucleotides that inhibit expression of specific oncogenes.  These oligonucleotides will be tested in humans within the next two years.  With Dr. Trent and Chaires, he has shown that common mutations in the telomerase gene promoter that occur in >75% of melanomas and glioblastomas cause destabilization of the DNA structure and prevent the gene from being “turned off”.  This normal regulation can be restored by oligonucleotides that stabilize the quadruplex structure in the “off” position.  This has obvious implications for melanoma treatment.

Literature Cited:

  1. 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.
  2. Bates, P.J., Kahlon, J.B., Thomas, S.D., Trent, J.O., Miller, D.M.:  Antiproliferative activity in G-rich oligonucleotides correlates with protein binding.  J Biol  Chem. 274:26369-77, 1999.
  3. 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 86(3):151-64, 2009; PMC2716701
  4. Sedoris KC, Thomas SD, Clarkson CR, Muench D, Islam A, Singh R, Miller DM: Genomic c-Myc Quadruplex DNA Selectively Kills Leukemia.  Mol Cancer Ther. 2012 Jan;11(1):66-76. [Epub 2011 Nov. 14]
  5. Schwartzentruber DJ, Lawson D, Richards J, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Bockaj B, Kendra K, White RL, Gonzalez R, Kuzel T, Curti B, Leming P, Whitman E, Balkisson J, Reintgen D, Kaufman H, Marincola F, Merino M, Choyke P, Vena D, Hwu P.   A phase III multi-institutional randomized study of immunization with gp100:209-217(210M) peptide followed by high dose IL-2 vs. IL-2 alone in patients with metastatic melanoma.  N Engl J Med., 2011;364(22):2119-27.
  6. 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.

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