Michael D. Cole, PhD
Professor of Molecular and Systems Biology
Molecular and Systems Biology
The Johns Hopkins University, PhD 1978
Ohio Northern University, BA 1973
Molecular and Cellular Biology Graduate Programs
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine
Rubin 633; HB7936
One Medical Center Drive
Dartmouth Medical School
Lebanon NH 03756
Office: Rubin 633
Assistant: Laboratory Contact
Asst. Phone: 603-653-9973
Studies of the genetic events involved in the induction of cancer provide an opportunity to define the molecular basis of the disease and to study the regulation and function of important eukaryotic genes that control cell proliferation. The c-myc gene encodes a transcription factor that is critical for progression through the cell cycle, and mutations that misregulate c-myc are frequently found in human and animal cancers. Our central research interest is to define the cellular target genes through which c-myc and other oncogenic transcription factors function and also the nuclear factors that mediate target gene and c-myc regulation.
A major area of interest is to identify the nuclear cofactors that facilitate Mycâ€™s ability to activate and repress target genes. Past studies showed that Myc recruits histone acetylation complexes to target sites, and more recent studies show that Myc also modulates transcriptional activity by increasing phosphorylation of the RNA polymerase II carboxy-terminal domain. Most recently, we identified a novel E3 ligase that binds directly to Myc to promote Myc protein degradation. Downregulation of this E3 ligase is common in most cancer cells, leading to higher levels of Myc which enhance growth rates. Ongoing studies are aimed at understanding the mechanism of Myc-mediated transcriptional repression which may involve enhanced repressive histone modifications.
A second major area of study involves distal regulatory elements that control the expression of c-myc and other genes relevant to cancer. We recently showed that an enhancer 330 kb upstream of the c-myc gene is an important regulator of c-myc expression in colon cancer cells and that this element functions through a large intrachromosomal loop that links it directly to the c-myc promoter. Furthermore, this distal element contains a polymorphism among humans that changes the predisposition to colon and prostate cancer.
PEMM 101/102 Scientific Basis of Disease (Course Director)
PEMM 126 Cancer Biology
Combining Fullerenes and Zwitterions in Non-Conjugated Polymer Interlayers to Raise Solar Cell Efficiency.
Chemical and Morphological Control of Interfacial Self-Doping for Efficient Organic Electronics.
Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration.
Inhibition of the Proteasome β2 Site Sensitizes Triple-Negative Breast Cancer Cells to β5 Inhibitors and Suppresses Nrf1 Activation.
HS3ST1 genotype regulates antithrombin's inflammomodulatory tone and associates with atherosclerosis.
MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-Catenin Signaling Transcripts By Recruiting CDK7 and RNA Methyltransferase.
Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk.
An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.
Strategically targeting MYC in cancer.
Ruptured Sinus of Valsalva Aneurysm into the Left Atrium with Multiple Fistulous Communications: A Rare Cause of Heart Failure.