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Michael D. Cole, Ph.D.

Title(s):
Professor of Pharmacology & Toxicology

Department(s):
Pharmacology & Toxicology

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/
http://geiselmed.dartmouth.edu/pharmtox/
http://www.cancer.dartmouth.edu/members/ColeM.shtml
http://www.dartmouth.edu/~mcb/

Contact Information:

Rubin 633; HB7936
One Medical Center Drive
Dartmouth Medical School
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:

 

Cole MD
MYC association with cancer risk and a new model of MYC-mediated repression.
Cold Spring Harb Perspect Med 2014 Jul 1; 4(7):a014316
PMID: 24985129

Davis CR, Toll EC, Bates AS, Cole MD, Smith FC
Surgical and procedural skills training at medical school - a national review.
Int J Surg 2014; 12(8):877-82
PMID: 24909137

Hu T, Pan Q, Andrew AS, Langer JM, Cole MD, Tomlinson CR, Karagas MR, Moore JH
Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.
BioData Min 2014 Apr 11; 7(1):5
PMID: 24725556

Gautam L, Sharratt SD, Cole MD
Drug facilitated sexual assault: detection and stability of benzodiazepines in spiked drinks using gas chromatography-mass spectrometry.
PLoS One 2014; 9(2):e89031
PMID: 24586489

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
PMID: 24013231

Abbott SC, Cole MD
Vibration arthrometry: a critical review.
Crit Rev Biomed Eng 2013; 41(3):223-42
PMID: 24579645

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
PMID: 23135913

Cowper-Sal lari R, Zhang X, Wright JB, Bailey SD, Cole MD, Eeckhoute J, Moore JH, Lupien M
Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression.
Nat Genet 2012 Nov; 44(11):1191-8
PMID: 23001124

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
PMID: 22186139

Schmucker AC, Wright JB, Cole MD, Brinckerhoff CE
Distal interleukin-1β (IL-1β) response element of human matrix metalloproteinase-13 (MMP-13) binds activator protein 1 (AP-1) transcription factors and regulates gene expression.
J Biol Chem 2012 Jan 6; 287(2):1189-97
PMID: 22102411