Edit Entry

Michael D. Cole, PhD

Title(s):
Professor of Pharmacology & Toxicology
Professor of Genetics

Department(s):
Pharmacology & Toxicology
Genetics

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:

 

MYC Mediates mRNA Cap Methylation of Canonical Wnt/beta-catenin Signaling Transcripts by Recruiting CDK7 and RNA Methyltransferase.
Posternak V, Ung MH, Cheng C, Cole MD
Mol Cancer Res. 2016 Nov 29; pii: molcanres.0247.2016. Epub 2016 Nov 29.
PMID: 27899423

Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk.
Pattison JM, Posternak V, Cole MD
Mol Cancer Res. 2016 Nov;14(11):1078-1086. Epub 2016 Aug 11.
PMID: 27514407

An intergenic risk locus containing an enhancer deletion in 2q35 modulates breast cancer risk by deregulating IGFBP5 expression.
Wyszynski A, Hong CC, Lam K, Michailidou K, Lytle C, Yao S, Zhang Y, Bolla MK, Wang Q, Dennis J, Hopper JL, Southey MC, Schmidt MK, Broeks A, Muir K, Lophatananon A, Fasching PA, Beckmann MW, Peto J, Dos-Santos-Silva I, Sawyer EJ, Tomlinson I, Burwinkel B, Marme F, Guenel P, Truong T, Bojesen SE, Nordestgaard BG, Gonzalez-Neira A, Benitez J, Neuhausen SL, Brenner H, Dieffenbach AK, Meindl A, Schmutzler RK, Brauch H, GENICA Network., Nevanlinna H, Khan S, Matsuo K, Ito H, Dork T, Bogdanova NV, Lindblom A, Margolin S, Mannermaa A, Kosma VM, kConFab Investigators., Australian Ovarian Cancer Study Group., Wu AH, Van Den Berg D, Lambrechts D, Wildiers H, Chang-Claude J, Rudolph A, Radice P, Peterlongo P, Couch FJ, Olson JE, Giles GG, Milne RL, Haiman CA, Henderson BE, Dumont M, Teo SH, Wong TY, Kristensen V, Zheng W, Long J, Winqvist R, Pylkas K, Andrulis IL, Knight JA, Devilee P, Seynaeve C, Garcia-Closas M, Figueroa J, Klevebring D, Czene K, Hooning MJ, van den Ouweland AM, Darabi H, Shu XO, Gao YT, Cox A, Blot W, Signorello LB, Shah M, Kang D, Choi JY, Hartman M, Miao H, Hamann U, Jakubowska A, Lubinski J, Sangrajrang S, McKay J, Toland AE, Yannoukakos D, Shen CY, Wu PE, Swerdlow A, Orr N, Simard J, Pharoah PD, Dunning AM, Chenevix-Trench G, Hall P, Bandera E, Amos C, Ambrosone C, Easton DF, Cole MD
Hum Mol Genet. 2016 Jul 11; pii: ddw223. Epub 2016 Jul 11.
PMID: 27402876

Strategically targeting MYC in cancer.
Posternak V, Cole MD
F1000Res. 2016 Mar 29;5 pii: F1000 Faculty Rev-408. doi: 10.12688/f1000research.7879.1. Epub 2016 Mar 29.
PMID: 27081479

Ruptured Sinus of Valsalva Aneurysm into the Left Atrium with Multiple Fistulous Communications: A Rare Cause of Heart Failure.
Agrawal Y, Chandrashekhar R, Pratt JW, Cole MD, Kamath S, Kalavakunta JK
Case Rep Cardiol. 2015;2015:627946. doi: 10.1155/2015/627946. Epub 2015 Dec 27.
PMID: 26819782

Retroviruses hijack chromatin loops to drive oncogene expression and highlight the chromatin architecture around proto-oncogenic loci.
Pattison JM, Wright JB, Cole MD
PLoS One. 2015 Mar 23;10(3):e0120256. doi: 10.1371/journal.pone.0120256. Epub 2015 Mar 23.
PMID: 25799187

MYC association with cancer risk and a new model of MYC-mediated repression.
Cole MD
Cold Spring Harb Perspect Med. 2014 Jul 1;4(7):a014316. doi: 10.1101/cshperspect.a014316. Epub 2014 Jul 1.
PMID: 24985129

Surgical and procedural skills training at medical school - a national review.
Davis CR, Toll EC, Bates AS, Cole MD, Smith FC
Int J Surg. 2014;12(8):877-82. doi: 10.1016/j.ijsu.2014.05.069. Epub 2014 Jun 5.
PMID: 24909137

Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.
Hu T, Pan Q, Andrew AS, Langer JM, Cole MD, Tomlinson CR, Karagas MR, Moore JH
BioData Min. 2014 Apr 11;7(1):5. doi: 10.1186/1756-0381-7-5. Epub 2014 Apr 11.
PMID: 24725556

Drug facilitated sexual assault: detection and stability of benzodiazepines in spiked drinks using gas chromatography-mass spectrometry.
Gautam L, Sharratt SD, Cole MD
PLoS One. 2014 Feb 19;9(2):e89031. doi: 10.1371/journal.pone.0089031. Epub 2014 Feb 19.
PMID: 24586489