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Michael D. Cole, PhD

Title(s):
Professor of Molecular and Systems Biology

Department(s):
Molecular and Systems Biology

Education:
The Johns Hopkins University, PhD 1978
Ohio Northern University, BA 1973

Programs:
Molecular and Cellular Biology Graduate Programs
Norris Cotton Cancer Center
Pharmacology and Toxicology Graduate Program
Program in Experimental and Molecular Medicine

Websites:
http://geiselmed.dartmouth.edu/colelab/
https://graduate.dartmouth.edu/mcb/
https://graduate.dartmouth.edu/pemm/

Contact Information:

Rubin 633; HB7936
One Medical Center Drive
Geisel School of Medicine
Lebanon NH 03756

Office: Rubin 633
Phone: 603-653-9975
Fax: 603-653-9952
Email: michael.cole@dartmouth.edu

Assistant: Laboratory Contact
Asst. Phone: 603-653-9973


Professional Interests:

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 Myc’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.

Courses Taught:

PEMM 101/102 Scientific Basis of Disease (Course Director)
PEMM 126 Cancer Biology


Selected Publications:

 

  • Gorlov IP, Pikielny CW, Frost HR, Her SC, Cole MD, Strohbehn SD, Wallace-Bradley D, Kimmel M, Gorlova OY, Amos CI. Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples. BMC Bioinformatics. 2018 Nov 19;19(1):430. (view details on MedLine)

  • Weyburne ES, Wilkins OM, Sha Z, Williams DA, Pletnev AA, de Bruin G, Overkleeft HS, Goldberg AL, Cole MD, Kisselev AF. Inhibition of the Proteasome β2 Site Sensitizes Triple-Negative Breast Cancer Cells to β5 Inhibitors and Suppresses Nrf1 Activation. Cell Chem Biol. 2017 Feb 16;24(2):218-230. (view details on MedLine)

  • Posternak V, Ung MH, Cheng C, Cole MD. MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-Catenin Signaling Transcripts By Recruiting CDK7 and RNA Methyltransferase. Mol Cancer Res. 2017 Feb;15(2):213-224. (view details on MedLine)

  • Pattison JM, Posternak V, Cole MD. Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk. Mol Cancer Res. 2016 Nov;14(11):1078-1086. (view details on MedLine)

  • Wyszynski A, Hong CC, Lam K, Michailidou K, Lytle C...Cole MD, et al. An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. Hum Mol Genet. 2016 Sep 1;25(17):3863-3876. (view details on MedLine)

  • Posternak V, Cole MD. Strategically targeting MYC in cancer. F1000Res. 2016 Mar 29;5. pii: F1000 Faculty Rev-408. (view details on MedLine)

  • Pattison JM, Wright JB, Cole MD. Retroviruses hijack chromatin loops to drive oncogene expression and highlight the chromatin architecture around proto-oncogenic loci. PLoS One. 2015 Mar 23;10(3):e0120256. (view details on MedLine)

  • Cowling VH, Turner SA, Cole MD. Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis. Oncogene. 2014 Jul 3;33(27):3519-27. (view details on MedLine)

  • Kaur M, Cole MD. MYC acts via the PTEN tumor suppressor to elicit autoregulation and genome-wide gene repression by activation of the Ezh2 methyltransferase. Cancer Res. 2013 Jan 15;73(2):695-705. (view details on MedLine)

  • Doe MR, Ascano JM, Kaur M, Cole MD. Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res. 2012 Feb 15;72(4):949-57. (view details on MedLine)

  • Posternak V, Ung MH, Cheng C, Cole MD. MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-Catenin Signaling Transcripts By Recruiting CDK7 and RNA Methyltransferase. Mol Cancer Res. 2017 Feb;15(2):213-224. (view details on MedLine)

  • Pattison JM, Posternak V, Cole MD. Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk. Mol Cancer Res. 2016 Nov;14(11):1078-1086. (view details on MedLine)

  • Wyszynski A, Hong CC, Lam K, Michailidou K, Lytle C...Cole MD, et al. An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression. Hum Mol Genet. 2016 Sep 1;25(17):3863-3876. (view details on MedLine)

  • Posternak V, Cole MD. Strategically targeting MYC in cancer. F1000Res. 2016 Mar 29;5. pii: F1000 Faculty Rev-408. (view details on MedLine)

  • Pattison JM, Wright JB, Cole MD. Retroviruses hijack chromatin loops to drive oncogene expression and highlight the chromatin architecture around proto-oncogenic loci. PLoS One. 2015 Mar 23;10(3):e0120256. (view details on MedLine)

  • Cowling VH, Turner SA, Cole MD. Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered target gene response and implicate Nol5a/Nop56 in oncogenesis. Oncogene. 2014 Jul 3;33(27):3519-27. (view details on MedLine)

  • Kaur M, Cole MD. MYC acts via the PTEN tumor suppressor to elicit autoregulation and genome-wide gene repression by activation of the Ezh2 methyltransferase. Cancer Res. 2013 Jan 15;73(2):695-705. (view details on MedLine)

  • Doe MR, Ascano JM, Kaur M, Cole MD. Myc posttranscriptionally induces HIF1 protein and target gene expression in normal and cancer cells. Cancer Res. 2012 Feb 15;72(4):949-57. (view details on MedLine)