Daniel L. Weeks, PhD

Portrait
Professor of Biochemistry
Professor of Pediatrics

Contact Information

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

Education

BS, Biological Sciences, Microbiology, Purdue University
PhD, Biological Sciences, Purdue University
Postdoctoral Fellow, Dept of Biochemistry and Molecular Biology, Harvard University

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Molecular Medicine, 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 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 that result. 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. Our most current studies look at how amyloids are used as part of normal development. The extracellular formation of amyloid particles is part of the pathogenesis that accompanies devastating diseases like Alzheimer’s and Huntington’s disease. However, it is increasingly clear that the formation of amyloids, most commonly the formation of proteins into cross-beta strand structures rather than their active, native three-dimensional structure, may be non-pathogenic and even advantageous. The best current examples of the formation of advantageous amyloid-like structures come from studies in yeast, where stress responsiveness and the ability to adapt to changing nutritional conditions are mediated thought the assembly and disassembly of amyloid-like structures. The formation of amyloid-like structures were also critical for long-term memory in studies using snails and fruit flies. As the features that allow a protein to form an amyloid as an alternative to it’s active structure become better understood the surprising result is that at least 5% of known proteins meet the requirements. We now know that in oocytes the nuclear particles where transcription and RNA processing occurs contain amyloids, and amyloids can be found in the nucleus and cytosol of the dividing cells of the early embryo. We are investigating what proteins are forming amyloids and how they are assembled and disassembled as part of normal development.

Publications

Li, Y., Manaligod, J. M. & Weeks, D. L. (2010). 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, 102(5), 277-92. PMID: 19951260.

Bartlett, H., Veenstra, G. J. & Weeks, D. L. (2010). Examining the cardiac NK-2 genes in early heart development. Pediatric cardiology, 31(3), 335-41. PMID: 19967350.

Allen, B. G., Weeks, D. L. (2009). Bacteriophage phiC31 integrase mediated transgenesis in Xenopus laevis for protein expression at endogenous levels. Methods in molecular biology (Clifton, N.J.), 518, 113-22. PMID: 19085128.

Chesneau, A., Sachs, L. M., Chai, N., Chen, Y., Du Pasquier, L., Loeber, J., Pollet, N., Reilly, M., Weeks, D. L. & Bronchain, O. J. (2008). Transgenesis procedures in Xenopus. Biology of the cell / under the auspices of the European Cell Biology Organization, 100(9), 503-21. PMID: 18699776.

Bartlett, H. L., Weeks, D. L. (2008). Lessons from the lily pad: Using Xenopus to understand heart disease. Drug discovery today. Disease models, 5(3), 141-146. PMID: 19802378.

Jacobi, U. G., Akkers, R. C., Pierson, E. S., Weeks, D. L., Dagle, J. M. & Veenstra, G. J. (2007). TBP paralogs accommodate metazoan- and vertebrate-specific developmental gene regulation. The EMBO journal, 26(17), 3900-9. PMID: 17703192.

Bartlett, H. L., Sutherland, L., Kolker, S. J., Welp, C., Tajchman, U., Desmarais, V. & Weeks, D. L. (2007). 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, 236(9), 2475-84. PMID: 17685485.

Mitchell, T., Jones, E. A., Weeks, D. L. & Sheets, M. D. (2007). Chordin affects pronephros development in Xenopus embryos by anteriorizing presomitic mesoderm. Developmental dynamics : an official publication of the American Association of Anatomists, 236(1), 251-61. PMID: 17106888.

Allen, B. G., Allen-Brady, K. & Weeks, D. L. (2006). Reduction of XNkx2-10 expression leads to anterior defects and malformation of the embryonic heart. Mechanisms of development, 123(10), 719-29. PMID: 16949797.

Collop, A. H., Broomfield, J. A., Chandraratna, R. A., Yong, Z., Deimling, S. J., Kolker, S. J., Weeks, D. L. & Drysdale, T. A. (2006). Retinoic acid signaling is essential for formation of the heart tube in Xenopus. Developmental biology, 291(1), 96-109. PMID: 16423341.

Hayes, M. H., Peuchen, E. H., Dovichi, N. J. & Weeks, D. L. (In Press). Dual roles for ATP in the regulation of phase separated protein aggregates in Xenopus oocyte nucleoli. eLife.

Hayes, M. H., Weeks, D. L. (2016). Amyloids assemble as part of recognizable structures during oogenesis in Xenopus. Biology open, 5(6), 801-6. PMID: 27215327.

Hayes, M. H., Weeks, D. L. (2016). Amyloids assemble as part of recognizable structures during oogenesis in Xenopus. Biology. DOI: 10.1242/bio.017384.

Gazdag, E., Jacobi, U., van Kruijsbergen, I., Weeks, D. L. & Veenstra, G. J. (2016). Activation of a T-box-Otx2-Gsc gene network independent of TBP and TBP-relatedfactors. (Vols. 143). pp. 130-135. Development. PMID: 26952988.

Gazdab, E., Allen, B. A., van Kruijsbergen, I., Weeks, D. L. & Veenstra, G. J. (2016). Activation of a t-box-Otx2-Gsc gene network independent of TBP and TBP-related factors. Development, 143, 130-1350.

Li, Y., Allen, B. & Weeks, D. (2012). Using phiC31 integrase to mediate insertion of DNA in Xenopus embryos. In S. Hoppler , P. Vize (Eds.) Methods in Molecular Biology. (2nd Edition) Xenopus Protocols, Post Genomic Approaches, Humana Press.

Li, Y. E., Allen, B. G. & Weeks, D. L. (2012). Using FC31 integrase to mediate insertion of DNA in Xenopus embryos. Methods in molecular biology (Clifton, N.J.), 917, 219-30. PMID: 22956091.

Allen, B. G., Weeks, D. L. (2006). Using phiC31 integrase to make transgenic Xenopus laevis embryos. Nature protocols, 1(3), 1248-57. PMID: 17406408.

Allen, B. G., Weeks, D. L. (2005). Transgenic Xenopus laevis embryos can be generated using phiC31 integrase. Nature methods, 2(12), 975-9. PMID: 16299484.

Bane, B. C., Van Rybroek, J. M., Kolker, S. J., Weeks, D. L. & Manaligod, J. M. (2005). EYA1 expression in the developing inner ear. The Annals of otology, rhinology, and laryngology, 114(11), 853-8. PMID: 16358604.

Slevin, M. K., Lyons-Levy, G., Weeks, D. L. & Hartley, R. S. (2005). Antisense knockdown of cyclin E does not affect the midblastula transition in Xenopus laevis embryos. Cell cycle (Georgetown, Tex.), 4(10), 1396-402. PMID: 16131839.

Knauert, M. P., Lloyd, J. A., Rogers, F. A., Datta, H. J., Bennett, M. L., Weeks, D. L. & Glazer, P. M. (2005). Distance and affinity dependence of triplex-induced recombination. Biochemistry, 44(10), 3856-64. PMID: 15751961.

Kalish, J. M., Seidman, M. M., Weeks, D. L. & Glazer, P. M. (2005). Triplex-induced recombination and repair in the pyrimidine motif. Nucleic acids research, 33(11), 3492-502. PMID: 15961731.

Jallow, Z., Jacobi, U. G., Weeks, D. L., Dawid, I. B. & Veenstra, G. J. (2004). 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, 101(37), 13525-30. PMID: 15345743.

Bartlett, H. L., Scholz, T. D., Lamb, F. S. & Weeks, D. L. (2004). Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging. American journal of physiology. Heart and circulatory physiology, 286(6), H2035-41. PMID: 15148055.

Dagle, J. M., Sabel, J. L., Littig, J. L., Sutherland, L. B., Kolker, S. J. & Weeks, D. L. (2003). Pitx2c attenuation results in cardiac defects and abnormalities of intestinal orientation in developing Xenopus laevis. Developmental biology, 262(2), 268-81. PMID: 14550790.

Hukriede, N. A., Tsang, T. E., Habas, R., Khoo, P. L., Steiner, K., Weeks, D. L., Tam, P. P. & Dawid, I. B. (2003). Conserved requirement of Lim1 function for cell movements during gastrulation. Developmental cell, 4(1), 83-94. PMID: 12530965.

Luo, T., Matsuo-Takasaki, M., Thomas, M. L., Weeks, D. L. & Sargent, T. D. (2002). Transcription factor AP-2 is an essential and direct regulator of epidermal development in Xenopus. Developmental biology, 245(1), 136-44. PMID: 11969261.

Dagle, J. M., Weeks, D. L. (2001). Oligonucleotide-based strategies to reduce gene expression. Differentiation; research in biological diversity, 69, 75-82. PMID: 11798068.

Vasquez, K. M., Dagle, J. M., Weeks, D. L. & Glazer, P. M. (2001). Chromosome targeting at short polypurine sites by cationic triplex-forming oligonucleotides. The Journal of biological chemistry, 276(42), 38536-41. PMID: 11504712.

Veenstra, G. J., Weeks, D. L. & Wolffe, A. P. (2000). Distinct roles for TBP and TBP-like factor in early embryonic gene transcription in Xenopus. Science (New York, N.Y.), 290(5500), 2312-5. PMID: 11125147.

Dagle, J. M., Littig, J. L., Sutherland, L. B. & Weeks, D. L. (2000). Targeted elimination of zygotic messages in Xenopus laevis embryos by modified oligonucleotides possessing terminal cationic linkages. Nucleic acids research, 28(10), 2153-7. PMID: 10773085.

Bailey, C., Weeks, D. L. (2000). Understanding oligonucleotide-mediated inhibition of gene expression in Xenopus laevis oocytes. Nucleic acids research, 28(5), 1154-61. PMID: 10666457.

Kolker, S. J., Tajchman, U. & Weeks, D. L. (2000). Confocal imaging of early heart development in Xenopus laevis. Developmental biology, 218(1), 64-73. PMID: 10644411.

Dagle, J. M., Weeks, D. L. (2000). Selective degradation of targeted mRNAs using partially modified oligonucleotides. pp. 420-36. Methods in enzymology. PMID: 10595370.

Askjaer, P., Bachi, A., Wilm, M., Bischoff, F. R., Weeks, D. L., Ogniewski, V., Ohno, M., Niehrs, C., Kjems, J., Mattaj, I. W. & Fornerod, M. (1999). RanGTP-regulated interactions of CRM1 with nucleoporins and a shuttling DEAD-box helicase. Molecular and cellular biology, 19(9), 6276-85. PMID: 10454574.

Runyan, R. B., Wendler, C. C., Romano, L. A., Boyer, A. S., Dagle, J. M. & Weeks, D. L. (1999). Utilization of antisense oligodeoxynucleotides with embryonic tissues in culture. Methods (San Diego, Calif.), 18(3), 316-21. PMID: 10454991.

Boyer, A. S., Ayerinskas, I. I., Vincent, E. B., McKinney, L. A., Weeks, D. L. & Runyan, R. B. (1999). TGFbeta2 and TGFbeta3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Developmental biology, 208(2), 530-45. PMID: 10191064.

Bailey, C. P., Dagle, J. M. & Weeks, D. L. (1998). Cationic oligonucleotides can mediate specific inhibition of gene expression in Xenopus oocytes. Nucleic acids research, 26(21), 4860-7. PMID: 9776745.

Vincent, E. B., Runyan, R. B. & Weeks, D. L. (1998). 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, 213(3), 237-47. PMID: 9825860.

Gururajan, R., Weeks, D. L. (1997). An3 protein encoded by a localized maternal mRNA in Xenopus laevis is an ATPase with substrate-specific RNA helicase activity. Biochimica et biophysica acta, 1350(2), 169-82. PMID: 9048887.

Longo, F. J., Mathews, L., Gururajan, R., Chen, J. & Weeks, D. L. (1996). Changes in nuclear localization of An3, a RNA helicase, during oogenesis and embryogenesis in Xenopus laevis. Molecular reproduction and development, 45(4), 491-502. PMID: 8956288.

Dagle, J. M., Weeks, D. L. (1996). Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation. Nucleic acids research, 24(11), 2143-9. PMID: 8668547.

Huang, J. X., Potts, J. D., Vincent, E. B., Weeks, D. L. & Runyan, R. B. (1995). Mechanisms of cell transformation in the embryonic heart. Annals of the New York Academy of Sciences, 752, 317-30. PMID: 7755277.

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

Gururajan, R., Mathews, L., Longo, F. J. & Weeks, D. L. (1994). 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, 91(6), 2056-60. PMID: 8134348.

Linnen, J. M., Bailey, C. P. & Weeks, D. L. (1993). Two related localized mRNAs from Xenopus laevis encode ubiquitin-like fusion proteins. Gene, 128(2), 181-8. PMID: 8390387.

Runyan, R. B., Potts, J. D. & Weeks, D. L. (1992). TGF-beta 3-mediated tissue interaction during embryonic heart development. Molecular reproduction and development, 32(2), 152-9. PMID: 1637553.

Potts, J. D., Vincent, E. B., Runyan, R. B. & Weeks, D. L. (1992). Sense and antisense TGF beta 3 mRNA levels correlate with cardiac valve induction. Developmental dynamics : an official publication of the American Association of Anatomists, 193(4), 340-5. PMID: 1511174.

Weeks, D. L., Walder, J. A. & Dagle, J. M. (1991). Cyclin B mRNA depletion only transiently inhibits the Xenopus embryonic cell cycle. Development (Cambridge, England), 111(4), 1173-8. PMID: 1831750.

Potts, J. D., Dagle, J. M., Walder, J. A., Weeks, D. L. & Runyan, R. B. (1991). 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, 88(4), 1516-20. PMID: 1996351.

Gururajan, R., Perry-O'Keefe, H., Melton, D. A. & Weeks, D. L. (1991). The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase. Nature, 349(6311), 717-9. PMID: 1996140.

Dagle, J. M., Weeks, D. L. & Walder, J. A. (1991). Pathways of degradation and mechanism of action of antisense oligonucleotides in Xenopus laevis embryos. Antisense research and development, 1(1), 11-20. PMID: 1668307.

Dagle, J. M., Walder, J. A. & Weeks, D. L. (1990). Targeted degradation of mRNA in Xenopus oocytes and embryos directed by modified oligonucleotides: studies of An2 and cyclin in embryogenesis. Nucleic acids research, 18(16), 4751-7. PMID: 1697675.

Weeks, D. L. (1990). Possible roles of localized maternal mRNAs in the development of Xenopus laevis. D. Stocum (Eds.) The Cellular and Molecular Biology of Pattern Formation.

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

Weeks, D. L., Melton, D. A. (1987). A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-beta. Cell, 51(5), 861-7. PMID: 3479264.

Weeks, D. L., Melton, D. A. (1987). 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, 84(9), 2798-802. PMID: 2953029.

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

Rebagliati, M. R., Weeks, D. L., Harvey, R. P. & Melton, D. A. (1985). Identification and cloning of localized maternal RNAs from Xenopus eggs. Cell, 42(3), 769-77. PMID: 2414011.

Weeks, D. L., Jones, N. C. (1985). Adenovirus E3-early promoter: sequences required for activation by E1A. Nucleic acids research, 13(14), 5389-402. PMID: 2991862.

Weeks, D. L., Rebagliati, M. R., Harvey, R. P. & Melton, D. A. (1985). Localized maternal mRNAs in Xenopus laevis eggs. Cold Spring Harbor symposia on quantitative biology, 50, 21-30. PMID: 3006987.

Jones, N. C., Richter, J. D., Weeks, D. L. & Smith, L. D. (1983). Regulation of adenovirus transcription by an E1a gene in microinjected Xenopus laevis oocytes. Molecular and cellular biology, 3(12), 2131-42. PMID: 6318084.

Weeks, D. L., Jones, N. C. (1983). E1A control of gene expression is mediated by sequences 5' to the transcriptional starts of the early viral genes. Molecular and cellular biology, 3(7), 1222-34. PMID: 6888379.

Weeks, D. L., LoVerde, P. T. & Williams, L. S. (1980). Development of Schistosoma mansoni: Enzyme levels during the transformatino from cercariae into schistosomule. (70) Journal of Parasitology.

Weeks, D. L., Donelson, J. E. Regulation of gene expression. T. Devlin (Eds.) in Textbook of Biochemistry with Clinical Correlations fifth, sixth and seventh editions, Wiley Press.