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.

Selected Publications

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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]

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