Miles F. Wilkinson, Ph.D.

1984, University of Warwick, England

UT M. D. Anderson Cancer Center
Biochemistry/Molecular Biology

Research Interests: gene regulation, RNAi, microRNAs, RNA surveillance, developmental biology, reproductive biology

The primary interests of my laboratory are: (1) transcriptional regulatory pathways that control embryonic stem-cell and germ-cell development in vivo, and (2) RNA surveillance pathways that serve as quality-control mechanisms to degrade or “correct” aberrant transcripts that would otherwise express truncated proteins causing developmental defects and cancer.

The Rhox homeobox genes . We recently discovered the largest known cluster of homeobox genes (containing at least 33 genes) in the mouse genome. We are studying the regulation and function of these Rhox genes in normal development and malignancy. Our goal is to understand how their transcription is controlled, to identify their downstream target genes, and to elucidate their biological functions in mice. To address these questions, we are using a variety of techniques, including a conditional in vivo RNA interference (RNAi) approach that we recently developed.

Nonsense-mediated decay (NMD) . Nonsense and frameshift mutations are present in about 1/3 of disease-causing genes. Transcripts containing such mutations are degraded by NMD. We are studying the underlying molecular mechanism for NMD, its regulation by microRNAs, and its physiological role in vivo. We are also studying other phenomena triggered by such mutations, including alterations in mRNA export and mRNA splicing.

For further details see: www3.mdanderson.org/public/genedev/public_html/wilkinson.html

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Wang, J., Vock, V.M., Olivas, O.R. & Wilkinson, M.F. (2002) A quality-control pathway that downregulates aberrant TCR transcripts by a mechanism requiring UPF2 and translation. J. Biol. Chem. 277:18,489-18,493.

Rao, M.K., Maiti, S., Ananthaswamy, H.N. & Wilkinson, M.F. (2002) A Highly Active Homeobox Gene Promoter Regulated by Ets and Sp1 Family Members in Normal Granulosa Cells and Diverse Tumor Cell Types. J. Biol. Chem. 277:26036-26045.

Rao, M.K., Wayne, C.M. & Wilkinson, M.F. (2002) Pem Homeobox Gene Regulatory Sequences that Direct Androgen-Dependent Developmentally Regulated Gene Expression in Different Subregions of the Epididymis. J. Biol. Chem. 277:48771-48778.

Gudikote, J.P. & Wilkinson, M.F. (2002) T-cell Receptor Sequences that elicit Strong Downregulation of Premature Termination Codon-bearing Transcripts. EMBO J. 21:125-134. Commentaries on this paper.

Wilkinson, M.F. & Shyu, A-B. (2002) RNA Surveillance by Nuclear Scanning? Nature Cell Biology 4: E144-147.

Wang, J., Chang, Y.-F., Hamilton, J.I & Wilkinson, M.F. (2002) Nonsense-Associated Altered Splicing: A Frame-Dependent Response Distinct from Nonsense-Mediated Decay. Mol. Cell 10:951-957. Commentary on this paper.

Wang, J., Hamilton, J.I., Carter, M.S., Li, S. & Wilkinson, M.F. (2002) Alternatively Spliced TCR mRNA Induced by Disruption of Reading Frame. Science 297:108-110. Commentaries on this paper.

Rao, M.K., Wayne, C.M., Meistrich, M.L. & Wilkinson, M.F. (2003) Pem Homeobox Gene Promoter Sequences that Direct Transcription in a Sertoli Cell-Specific, Stage-Specific, and Androgen-Dependent Manner in the Testis In Vivo. Mol. Endocrinol. 17:223-233.

Wilkinson, M.F. (2003) The Cycle of Nonsense. Mol. Cell 12: 1059-1061.

Inoue, K., Khajavi, M., Ohyama, T., Hirabayashi, S., Wilson, J., Reggin, J.D., Mancias, P., Butler, I.J., Wilkinson, M.F., Wegner, M. & Lupski, J.R. (2004) Molecular Mechanism for Distinct Neurological Phenotypes Conveyed by Allelic Truncating Mutations. Nature Genetics 36: 361-369. Commentaries on this paper.

Wilkinson, M.F. (2005) A New Function for Nonsense-Mediated Decay Factors. Trends in Genetics 21:143-148.

Bhardwaj, A. & Wilkinson M.F. (2005) , A Metabolic Enzyme Doing Double Duty as a Transcription Factor. BioEssays 27:467-471.

MacLean, J.A., Chen, M.A., Wayne, C.M., Bruce, S.R., Meistrich, M.L., Macleod, C.L. & Wilkinson, M.F. (2005) Rhox: A New Homeobox Gene Cluster. Cell 120:369-382. Commentaries on this paper.

Bruce, S. & Wilkinson, M.F. (2005) RNA Stability. In: "Genomics and Proteomics in Molecular Medicine," Ganten, D. & Ruckpaul, K., ed., Springer International.

Li, S., Wilkinson M.F., Xia, X., David, M., Xu, L., Purkel-Sutton, A. & Bhardwaj, A. (2005) Induction of IFN-Regulated Factors and Antitumoral Surveillance by Transfected Placebo Plasmid DNA. Molecular Therapy 11:112-119.

MacLean, J.A. & Wilkinson, M.F. (2005) Gene Regulation in Spermatogenesis. In: "Current Trends in Developmental Biology" 71:131-197.

Sims-Mourtada, J.C., Bruce, S., McKeller, M.R., Rangel, R., Guzman-Rojas, L., Cain, K., Lopez, C., Zimonjic D.B., Popescu, N.C., Gordon, J., Wilkinson, M.F. & Hector Martinez-Valdez (2005) The Human AKNA Gene Expresses Multiple Transcripts and Protein Isoforms as a Result of Alternative Promoter Usage, Splicing, and Polyadenylation. DNA & Cell Biology 24:325-328.

Gudikote J. & Wilkinson, M.F. (2005) Nonsense-Mediated Decay and the Immune System. In: "The Nonsense-Mediated Decay RNA Surveillance Pathway," Maquat, L.E., ed., Landes Biosciences.

MacLean, J.A., Rao, M.K., Doyle, M.H., Richards, J.S. & Wilkinson, M.F. (2005) Regulation of the Rhox5 Homeobox Gene in Primary Granulosa Cells:
Preovulatory Expression and Dependence on Sp1/Sp3 and Gabp. Biology of Reproduction 73:1126-1134.

Gudikote, J.P., Imam, J.S., Garcia, R.F. & Wilkinson, M.F. (2005) RNA Splicing Promotes Translation and RNA Surveillance. Nature Structural & Molecular Biology 12:801-809.

Rao, M., Pham, J., Imam, J.S., MacLean, J.A., Murali, D., Furuta, Y., Sinha-Hikim, A.P. & Wilkinson, M.F. (2006) Tissue-Specific RNAi Reveals that WT1 Expression in Nurse Cells Controls Germ-Cell Survival and Spermatogenesis Genes & Development 20:147-12. Commentaries on this paper.

MacLean, J.A., Lorenzetti, D., Hu, Z., Salerno, W.J., Miller, J. & Wilkinson, M.F. (2006) The Rhox Homeobox Gene Cluster: Recent Duplication of Three Family Members. Genesis 44:122-129.

Wang, W., Cajigas, I.J., García, E.J., Peltz, S.W., Wilkinson, M.F. & González, C.I. (2006) A Role for Upf2p Phosphorylation in Saccharomyces cerevisiae Nonsense-Mediated mRNA Decay. Molecular & Cellular Biology 26:3390-3400.

Bruno, I. & Wilkinson, M.F. (2006) P-bodies React to Stress and Nonsense. Cell 125:1036-1038.

Rao M, Wilkinson MF (2006) Tissue- and Cell Type-Specific RNA Interference In Vivo. Nature Protocols 1:1494-1501.

Rao M & Wilkinson MF (2006) “RNAi as a Tool to Silence Genes of Interest in Specific Tissues or Cell Types,” in Touch Briefings/Drug Discovery 2006: pp 35-36.

Chang Y-F, Imam JS & Wilkinson MF (2007) “The Nonsense-Mediated Decay RNA Surveillance Pathway,” Annual Review of Biochemistry, Ed.: Kornberg, R., Annual Reviews Inc.

Program Affiliations:
Program in Immunology
Program in Genes and Development