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Mark T. Bedford, Ph.D.

Present Title & Affiliation

Primary Appointment

Professor, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX

Research Interests

We study the intersection between epigenetics and cancer with a specific focus on one class of epigenetic mark - arginine methylation. To better understand the biological roles of arginine methylation, our research group uses a number of different biological approaches to interrogate PRMT function. These include mouse gain- and loss-of-function PRMT models, protein microarrays screens for methyl-binding proteins, biochemical screens for PRMT substrates, and screens for chemical inhibitors of PRMT family members.We have generated targeted disruptions of a number of arginine methyltransferase genes in mice in the hopes of unmasking cellular and tissue-specific roles for this post-translational modification. In-hand we currently have CARM1, PRMT3 and PRMT6 null mice. We are performing transcriptome analysis (RNA-seq) and ChIP-seq on these null mice to identify the repertoire of genes that they regulate. We are also performing double knockouts to investigate redundancy between the different PRMTs.We are also generating gain-of-function transgenic mouse models to determine the effects of PRMT overexpression in vivo. These are transgenic mice that can be activated by crossing to a tissue-specific cre line. The Cre expression removes a lox/STOP/los cassette and activates expression of the PRMT. We have already generated PRMT6 gain-of-function mice using this approach. We are currently producing CARM1, PRMT1, PRMT5 and TDRD3 transgenic mice using the same approach.

Office Address

Email: mtbedford@mdanderson.org

Education & Training

Degree-Granting Education

1996 Weizmann Institute of Science, Israel, PHD, Developmental Biology
1989 University of Stellenbosch, South Africa, MS, Medical Biochemistry
1986 University of Stellenbosch, South Africa, BS, Honors in Biochemistry
1985 University of Stellenbosch, South Africa, BS

Postgraduate Training

1996-2000 Postdoctoral Fellowship, Harvard Medical School, Boston, MA, Dr. Philip Leder

Experience/Service

Academic Appointments

Associate Professor, Department of Molecular Carcinogenesis, Science Park, The University of Texas MD Anderson Cancer Center, Smithville, TX, 2006-2011

Selected Publications

Peer-Reviewed Original Research Articles

1. Esteve PO, Terragni J, Deepti K, Chin HG, Dai N, Espejo A, Correa I Jr, Bedford MT, Pradhan S. Methyllysine reader PHD finger protein 20-like 1 antagonizes DNA (cytosine-5) methyltransferase 1 proteasomal degradation. J Biol Chem 289(12):8277-8287, 3/2014. PMCID: PMC3961655.
2. Gayatri S, Bedford MT. Readers of histone methylarginine marks. Biochim Biophys Acta. e-Pub 2/2014.
3. Guo A, Gu H, Zhou J, Mulhern D, Wang Y, Lee KA, Yang V, Aguiar M, Kornhauser J, Jia X, Ren J, Beausoleil SA, Silva JC, Vemulapalli V, Bedford MT, Comb MJ. Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol Cell Proteomics 13(1):372-387, 1/2014. PMCID: PMC3879628.
4. Yang Y, McBride KM, Hensley S, Lu Y, Chedin F, Bedford MT. Arginine methylation facilitates the recruitment of TOP3B to chromatin to prevent R loop accumulation. Mol Cell 53(3):484-97, 2014. PMCID: PMC3959860.
5. Zheng S, Moehlenbrink J, Lu YC, Zalmas LP, Sagum CA, Carr S, McGouran JF, Alexander L, Fedorov O, Munro S, Kessler B, Bedford MT, Yu Q, La Thangue NB. Arginine methylation-dependent reader-writer interplay governs growth control by E2F-1. Mol Cell 52(1):37-51, 2013.
6. Dhar S, Vemulapalli V, Patananan AN, Huang G, DiLorenzo A, Richard S, Comb MJ, Guo A, Clarke SG, Bedford MT. Loss of the major Type I arginine methyltransferase PRMT1 causes substrate scavenging by other PRMTs. Sci Rep 3:1311, 2013. PMCID: PMC3575585.
7. Badeaux AI, Yang Y, Cardenas K, Vemulapalli V, Chen K, Kusewitt D, Richie E, Li W, Bedford MT. Loss of the methyl lysine effector protein PHF20 impacts the expression of genes regulated by the lysine acetyltransferase MOF. J Biol Chem 287(1):429-37, 1/2012. PMCID: PMC3249094.
8. Zhao H, Ho PC, Lo YH, Espejo A, Bedford MT, Hung MC, Wang SC. Interaction of proliferation cell nuclear antigen (PCNA) with c-Abl in cell proliferation and response to DNA damages in breast cancer. PLoS One 7(1):e29416, 2012. PMCID: PMC3251568.
9. Calnan DR, Webb AE, White JL, Stowe TR, Goswami T, Shi X, Espejo A, Bedford MT, Gozani O, Gygi SP, Brunet A. Methylation by Set9 modulates FoxO3 stability and transcriptional activity. Aging (Albany NY) 4(7):462-79, 2012. PMCID: PMC3433933.
10. Cui G, Park S, Badeaux AI, Kim D, Lee J, Thompson JR, Yan F, Kaneko S, Yuan Z, Botuyan MV, Bedford MT*, Cheng JQ*, Mer G*. (*Corresponding Authors). PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53. Nat Struct Mol Biol 19(9):916-24, 2012. PMCID: PMC3454513.
11. Spannhoff A, Kim YK, Raynal NJ, Gharibyan V, Su MB, Zhou YY, Li J, Castellano S, Sbardella G, Issa JP, Bedford MT. Histone deacetylase inhibitor activity in royal jelly might facilitate caste switching in bees. EMBO Rep 12(3):238-43, 2011. PMCID: PMC3059907.
12. Yang Y, Lu Y, Espejo A, Wu J, Xu W, Liang S, Bedford MT. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol Cell 40(6):1016-23, 2010. PMCID: PMC3090733.

Invited Articles

1. Yang Y, Bedford MT. Protein arginine methyltransferases and cancer. Nat Rev Cancer 13(1):37-50, 2013. PMID: 23235912.
2. Yang Y, Bedford MT. Titivated for destruction: the methyl degron. Mol Cell 48(4):487-8, 2012. PMCID: PMC3563253.
3. Bedford MT, Clarke SG. Protein arginine methylation in mammals: Who, what, and why. Mol Cell 33(1):1-13, 1/2009. NIHMSID: NIHMS92204.

Book Chapters

1. Cheng D, Vemulapalli V, Bedford MT. Methods applied to the study of protein arginine methylation. In: Methods Enzymol. 512, 71-92, 2012. ISBN: 22910203.

Last updated: 6/4/2014