Stead Family Department of Pediatrics

Daniel Weeks, PhD

Portrait

Professor of Biochemistry
Professor of Pediatrics

Contact Information

Primary Office: 4-710 BSB
Iowa City, IA 52242
Primary Office Phone: 319-335-7918

Email: daniel-weeks@uiowa.edu
Web: Weeks Laboratory

Education

BS, Biological Sciences, Microbiology, Purdue University
PhD, Biological Sciences, Purdue University

Post Doctoral, Dept of Biochemistry and Molecular Biology, Harvard University

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Biochemistry PhD
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

We take advantage of the conservation of developmental control of embryogenesis among organisms, to study the function of genes involved in congenital defects in humans by doing experiments with the frog Xenopus laevis. We have been especially interested in genes that cause congenital defects in heart and ear development in humans. We take advantage of the relative ease of introduction of biomolecules like antisense oligonucleotides to reduce mRNA levels, or mRNA itself to make altered or increased levels of specific protein in live embryos. We then look for morphological and molecular changes in organs like the heart and ears. One of the techniques we use is whole mount immunohistochemistry coupled to confocal microscopy. Xenopus embryos develop rapidly and are small enough to use for confocal microscopic analysis that allows both the exterior and the interior of developing organ system to be viewed. We are designing, synthesizing and testing novel modifications of oligonucleotides to provide new ways to interfere with gene transcription and also to promote site directed mutations. In this approach we use oligonucleotides to form a three-stranded helix with sites in chromosomes. The three-stranded helix is formed through hydrogen bonds between h purines in the major groove of chromosomal DNA and the oligonucleotide. The formation of the triple helix may block transcription, prevent the sequence specific interactions of proteins that also hydrogen bond to purines in the major groove, or be used to direct site-specific DNA damage. Finally we are one of the laboratories that have taken the lead in using new methods to efficiently generate transgenic embryos. Again, using Xenopus embryos we have introduced reporter genes to study regulation of cell fate, and investigate mutations that lead to congenital defects.

All Publications

Li Y, Allen B, Weeks D.  Using ΦC31 integrase to mediate insertion of DNA in Xenopus embryos.  Methods in molecular biology (Clifton, N.J.).  2012. 917:219-30.
[PubMed]

Li Y, Manaligod J, Weeks D.  EYA1 mutations associated with the branchio-oto-renal syndrome result in defective otic development in Xenopus laevis.  Biology of the cell / under the auspices of the European Cell Biology Organization.  2010 May. 102(5):277-92.
[PubMed]

Bartlett H, Veenstra G, Weeks D.  Examining the cardiac NK-2 genes in early heart development.  Pediatric cardiology.  2010 April. 31(3):335-41.
[PubMed]

Allen B, Weeks D.  Bacteriophage phiC31 integrase mediated transgenesis in Xenopus laevis for protein expression at endogenous levels.  Methods in molecular biology (Clifton, N.J.).  2009. 518:113-22.
[PubMed]

Chesneau A, Sachs L, Chai N, Chen Y, Du Pasquier L, Loeber J, Pollet N, Reilly M, Weeks D, Bronchain O.  Transgenesis procedures in Xenopus.  Biology of the cell / under the auspices of the European Cell Biology Organization.  2008 September. 100(9):503-21.
[PubMed]

Bartlett H, Weeks D.  Lessons from the lily pad: Using Xenopus to understand heart disease.  Drug discovery today. Disease models.  2008. 5(3):141-146.
[PubMed]

Jacobi U, Akkers R, Pierson E, Weeks D, Dagle J, Veenstra G.  TBP paralogs accommodate metazoan- and vertebrate-specific developmental gene regulation.  The EMBO journal.  2007 September. 26(17):3900-9.
[PubMed]

Bartlett H, Sutherland L, Kolker S, Welp C, Tajchman U, Desmarais V, Weeks D.  Transient early embryonic expression of Nkx2-5 mutations linked to congenital heart defects in human causes heart defects in Xenopus laevis.  Developmental dynamics : an official publication of the American Association of Anatomists.  2007 September. 236(9):2475-84.
[PubMed]

Mitchell T, Jones E, Weeks D, Sheets M.  Chordin affects pronephros development in Xenopus embryos by anteriorizing presomitic mesoderm.  Developmental dynamics : an official publication of the American Association of Anatomists.  2007 January. 236(1):251-61.
[PubMed]

Allen B, Allen-Brady K, Weeks D.  Reduction of XNkx2-10 expression leads to anterior defects and malformation of the embryonic heart.  Mechanisms of development.  2006 October. 123(10):719-29.
[PubMed]

Collop A, Broomfield J, Chandraratna R, Yong Z, Deimling S, Kolker S, Weeks D, Drysdale T.  Retinoic acid signaling is essential for formation of the heart tube in Xenopus.  Developmental biology.  2006 March. 291(1):96-109.
[PubMed]

Allen B, Weeks D.  Using phiC31 integrase to make transgenic Xenopus laevis embryos.  Nature protocols.  2006. 1(3):1248-57.
[PubMed]

Allen B, Weeks D.  Transgenic Xenopus laevis embryos can be generated using phiC31 integrase.  Nature methods.  2005 December. 2(12):975-9.
[PubMed]

Bane B, Van Rybroek J, Kolker S, Weeks D, Manaligod J.  EYA1 expression in the developing inner ear.  The Annals of otology, rhinology, and laryngology.  2005 November. 114(11):853-8.
[PubMed]

Slevin M, Lyons-Levy G, Weeks D, Hartley R.  Antisense knockdown of cyclin E does not affect the midblastula transition in Xenopus laevis embryos.  Cell cycle (Georgetown, Tex.).  2005 October. 4(10):1396-402.
[PubMed]

Knauert M, Lloyd J, Rogers F, Datta H, Bennett M, Weeks D, Glazer P.  Distance and affinity dependence of triplex-induced recombination.  Biochemistry.  2005 March. 44(10):3856-64.
[PubMed]

Kalish J, Seidman M, Weeks D, Glazer P.  Triplex-induced recombination and repair in the pyrimidine motif.  Nucleic acids research.  2005. 33(11):3492-502.
[PubMed]

Jallow Z, Jacobi U, Weeks D, Dawid I, Veenstra G.  Specialized and redundant roles of TBP and a vertebrate-specific TBP paralog in embryonic gene regulation in Xenopus.  Proceedings of the National Academy of Sciences of the United States of America.  2004 September. 101(37):13525-30.
[PubMed]

Bartlett H, Scholz T, Lamb F, Weeks D.  Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging.  American journal of physiology. Heart and circulatory physiology.  2004 June. 286(6):H2035-41.
[PubMed]

Dagle J, Sabel J, Littig J, Sutherland L, Kolker S, Weeks D.  Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis.  Developmental biology.  2003 October. 262(2):268-81.
[PubMed]

Hukriede N, Tsang T, Habas R, Khoo P, Steiner K, Weeks D, Tam P, Dawid I.  Conserved requirement of Lim1 function for cell movements during gastrulation.  Developmental cell.  2003 January. 4(1):83-94.
[PubMed]

Luo T, Matsuo-Takasaki M, Thomas M, Weeks D, Sargent T.  Transcription factor AP-2 is an essential and direct regulator of epidermal development in Xenopus.  Developmental biology.  2002 May. 245(1):136-44.
[PubMed]

Dagle J, Weeks D.  Oligonucleotide-based strategies to reduce gene expression.  Differentiation; research in biological diversity.  2001 December. 69:75-82.
[PubMed]

Vasquez K, Dagle J, Weeks D, Glazer P.  Chromosome targeting at short polypurine sites by cationic triplex-forming oligonucleotides.  The Journal of biological chemistry.  2001 October. 276(42):38536-41.
[PubMed]

Veenstra G, Weeks D, Wolffe A.  Distinct roles for TBP and TBP-like factor in early embryonic gene transcription in Xenopus.  Science (New York, N.Y.).  2000 December. 290(5500):2312-5.
[PubMed]

Dagle J, Littig J, Sutherland L, Weeks D.  Targeted elimination of zygotic messages in Xenopus laevis embryos by modified oligonucleotides possessing terminal cationic linkages.  Nucleic acids research.  2000 May. 28(10):2153-7.
[PubMed]

Bailey C, Weeks D.  Understanding oligonucleotide-mediated inhibition of gene expression in Xenopus laevis oocytes.  Nucleic acids research.  2000 March. 28(5):1154-61.
[PubMed]

Kolker S, Tajchman U, Weeks D.  Confocal imaging of early heart development in Xenopus laevis.  Developmental biology.  2000 February. 218(1):64-73.
[PubMed]

Dagle J, Weeks D.  Selective degradation of targeted mRNAs using partially modified oligonucleotides.  Methods in enzymology.  2000. 313:420-36.
[PubMed]

Askjaer P, Bachi A, Wilm M, Bischoff F, Weeks D, Ogniewski V, Ohno M, Niehrs C, Kjems J, Mattaj I, Fornerod M.  RanGTP-regulated interactions of CRM1 with nucleoporins and a shuttling DEAD-box helicase.  Molecular and cellular biology.  1999 September. 19(9):6276-85.
[PubMed]

Runyan R, Wendler C, Romano L, Boyer A, Dagle J, Weeks D.  Utilization of antisense oligodeoxynucleotides with embryonic tissues in culture.  Methods (San Diego, Calif.).  1999 July. 18(3):316-21.
[PubMed]

Boyer A, Ayerinskas I, Vincent E, McKinney L, Weeks D, Runyan R.  TGFbeta2 and TGFbeta3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart.  Developmental biology.  1999 April. 208(2):530-45.
[PubMed]

Bailey C, Dagle J, Weeks D.  Cationic oligonucleotides can mediate specific inhibition of gene expression in Xenopus oocytes.  Nucleic acids research.  1998 November. 26(21):4860-7.
[PubMed]

Vincent E, Runyan R, Weeks D.  Production of the transforming growth factor-beta binding protein endoglin is regulated during chick heart development.  Developmental dynamics : an official publication of the American Association of Anatomists.  1998 November. 213(3):237-47.
[PubMed]

Gururajan R, Weeks D.  An3 protein encoded by a localized maternal mRNA in Xenopus laevis is an ATPase with substrate-specific RNA helicase activity.  Biochimica et biophysica acta.  1997 February. 1350(2):169-82.
[PubMed]

Longo F, Mathews L, Gururajan R, Chen J, Weeks D.  Changes in nuclear localization of An3, a RNA helicase, during oogenesis and embryogenesis in Xenopus laevis.  Molecular reproduction and development.  1996 December. 45(4):491-502.
[PubMed]

Dagle J, Weeks D.  Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation.  Nucleic acids research.  1996 June. 24(11):2143-9.
[PubMed]

Huang J, Potts J, Vincent E, Weeks D, Runyan R.  Mechanisms of cell transformation in the embryonic heart.  Annals of the New York Academy of Sciences.  1995 March. 752:317-30.
[PubMed]

Weeks D, Bailey C, Bullock E, Dagle J, Gururajan R, Linnin J, Longo F.  mRNA localized to the anumal hemisphere of Xenopus laevis oocytes and early embryos and the proteins that they encode.  Localized RNAs: Molecular Biology Intelligence Unit Series, R.G. Landes Co. of Biomedial Publishers, Austin, TX.  1995. 

Gururajan R, Mathews L, Longo F, Weeks D.  An3 mRNA encodes an RNA helicase that colocalizes with nucleoli in Xenopus oocytes in a stage-specific manner.  Proceedings of the National Academy of Sciences of the United States of America.  1994 March. 91(6):2056-60.
[PubMed]

Linnen J, Bailey C, Weeks D.  Two related localized mRNAs from Xenopus laevis encode ubiquitin-like fusion proteins.  Gene.  1993 June. 128(2):181-8.
[PubMed]

Runyan R, Potts J, Weeks D.  TGF-beta 3-mediated tissue interaction during embryonic heart development.  Molecular reproduction and development.  1992 June. 32(2):152-9.
[PubMed]

Potts J, Vincent E, Runyan R, Weeks D.  Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction.  Developmental dynamics : an official publication of the American Association of Anatomists.  1992 April. 193(4):340-5.
[PubMed]

Weeks D, Walder J, Dagle J.  Cyclin B mRNA depletion only transiently inhibits the Xenopus embryonic cell cycle.  Development (Cambridge, England).  1991 April. 111(4):1173-8.
[PubMed]

Potts J, Dagle J, Walder J, Weeks D, Runyan R.  Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3.  Proceedings of the National Academy of Sciences of the United States of America.  1991 February. 88(4):1516-20.
[PubMed]

Gururajan R, Perry-O'Keefe H, Melton D, Weeks D.  The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase.  Nature.  1991 February. 349(6311):717-9.
[PubMed]

Dagle J, Weeks D, Walder J.  Pathways of degradation and mechanism of action of antisense oligonucleotides in Xenopus laevis embryos.  Antisense research and development.  1991. 1(1):11-20.
[PubMed]

Dagle J, Walder J, Weeks D.  Targeted degradation of mRNA in Xenopus oocytes and embryos directed by modified oligonucleotides: studies of An2 and cyclin in embryogenesis.  Nucleic acids research.  1990 August. 18(16):4751-7.
[PubMed]

Weeks D.  Possible roles of localized maternal mRNAs in the development of Xenopus laevis.  The Cellular and Molecular Biology of Pattern Formation.  1990. 

Runyan R, Potts J, Weeks D, Sharma R, Loeber C, Chiang J, Bhalla R.  Tissue interaction and signal transduction in the atrioventricular canal of the embryonic heart.  Annual New York Academy of Science.  1990. 588:442-43.

Weeks D, Melton D.  A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-beta.  Cell.  1987 December. 51(5):861-7.
[PubMed]

Weeks D, Melton D.  A maternal mRNA localized to the animal pole of Xenopus eggs encodes a subunit of mitochondrial ATPase.  Proceedings of the National Academy of Sciences of the United States of America.  1987 May. 84(9):2798-802.
[PubMed]

Krieg P, Rebagliati M, Weeks D, Melton D.  Gene activation during Xenopus embryogenesis in gastrulation and embryo.  Alan R. Liss, Inc.  1986. 

Rebagliati M, Weeks D, Harvey R, Melton D.  Identification and cloning of localized maternal RNAs from Xenopus eggs.  Cell.  1985 October. 42(3):769-77.
[PubMed]

Weeks D, Jones N.  Adenovirus E3-early promoter: sequences required for activation by E1A.  Nucleic acids research.  1985 July. 13(14):5389-402.
[PubMed]

Weeks D, Rebagliati M, Harvey R, Melton D.  Localized maternal mRNAs in Xenopus laevis eggs.  Cold Spring Harbor symposia on quantitative biology.  1985. 50:21-30.
[PubMed]

Jones N, Richter J, Weeks D, Smith L.  Regulation of adenovirus transcription by an E1a gene in microinjected Xenopus laevis oocytes.  Molecular and cellular biology.  1983 December. 3(12):2131-42.
[PubMed]

Weeks D, Jones N.  E1A control of gene expression is mediated by sequences 5' to the transcriptional starts of the early viral genes.  Molecular and cellular biology.  1983 July. 3(7):1222-34.
[PubMed]

Weeks D, Donelson J.  Regulation of gene expression.  in Textbook of Biochemistry with Clinical Correlations fifth, sixth and seventh editions, Wiley Press. 

Date Last Modified: 06/07/2014 - 21:56:23