Donald M. Miller, M.D., Ph.D.
Director, M.D. / Ph.D. Program
Duke University
Additional Training
Peter Bent Brigham Hospital; Harvard University, Boston, MA
National Heart Lung Blood Institute; NIH, Bethesda, MD
National Cancer Institute, NIH, Bethesda, MD
Summary of Research Interests
Dr. Miller's laboratory has a longstanding interest in modulation of gene expression as a potential anticancer therapy. They have demonstrated that formation of triple helical DNA complexes inhibits in vitro transcription in a "gene-specific" manner. During the past several years, they have characterized the growth inhibitory activity of a set of four-stranded "G-quartet" forming oligonucleotides that bind to DNA helicase IV (nucleolin). These compact oligonucleotides inhibit growth of a variety of cancer cell types and appear to have little if any toxicity. Dr. Miller's group is now characterizing the interaction of the GRO's with nucleolin with the goal of designing small molecules which will inhitit cellular proliferation in the same manner.
In additional to the work with G-rich oligonucleotides, Dr. Miller's laboratory is studying the regulation of alpha-enolase, a glycolytic pathway enzyme. His group discovered an alternative translation product of alpha-enolase (MBP-1) which binds to the c-myc promoter and functions as a tumor suppressor. MBP-1, which is translated from alpha-enolase mRNA, does not have enolase activity and does not form homodimers.
Alpha-enolase on the other hand, does not have growth inhibitory characteristics, forms homodimers and does not bind the c-myc promoter. The mechanism by which the expression of these two proteins are regulated at the translational level is currently being investigated. This unique system represents an interesting intersection between the pathways of energy metabolism and growth regulation.
Telephone: 502-562-4585
