Person
Miller, Rachel K
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Biography and Research Interest
Numerous organ systems require development of tubular structures, including the gastrointestinal, urogenital and respiratory systems. Tubes enable transport, absorption and secretion of fluids and gases. Development of organs with precise structures requires coordination of cell movements. We are focusing on in mechanisms by which cells are shaped and morphogenesis is coordinated to produce defined tissue forms.
We utilize frog (Xenopus) embryonic kidneys and mammalian cultured cells as models. The tubules and duct of the nephron form the simplest unit of filtration in the kidney. While mammalian kidneys possess one million nephrons, each frog embryonic kidney has only one nephron, providing a simplified system to study organogenesis. Knockdown strategies and confocal imaging are used to assess tubulogenesis.
Altered Wnt signaling results in kidney pathologies including cystic kidney diseases and cancer. Our studies focus on how Wnt signaling modulates cell shape and organization to facilitate the formation of nephric tubules. Cells perceive their orientation within a tissue through a specific Wnt signaling pathway called planar cell polarity (PCP). Our studies focus on how PCP components with cytoskeletal roles regulate tubulogenesis.
Cystic kidneys are the most common feature of a group of genetic diseases known as ciliopathies. More than 20 of these disorders have been identified, and they are characterized by developmental defects causing blindness, deafness, chronic respiratory infections, kidney disease, heart disease, infertility, obesity, diabetes, polydactyly and situs inversus among others. Ciliopathies result from defects in cilia, including the primary cilia projecting into nephron lumens. Primary cilia act as cellular antennae, orchestrating cellular signaling and orienting cells through PCP. We are interested in the role of PCP and primary cilia in shaping nephric tubules.
Current interests in the lab include:
1) Determining how PCP components affect tubule and cilia formation
2) Discovering novel components affecting nephron development
3) Visualizing in vivo tube formation using advanced live imaging techniques
4) Generating transgenic animals to visualize nephrogenesis in vivo
We utilize frog (Xenopus) embryonic kidneys and mammalian cultured cells as models. The tubules and duct of the nephron form the simplest unit of filtration in the kidney. While mammalian kidneys possess one million nephrons, each frog embryonic kidney has only one nephron, providing a simplified system to study organogenesis. Knockdown strategies and confocal imaging are used to assess tubulogenesis.
Altered Wnt signaling results in kidney pathologies including cystic kidney diseases and cancer. Our studies focus on how Wnt signaling modulates cell shape and organization to facilitate the formation of nephric tubules. Cells perceive their orientation within a tissue through a specific Wnt signaling pathway called planar cell polarity (PCP). Our studies focus on how PCP components with cytoskeletal roles regulate tubulogenesis.
Cystic kidneys are the most common feature of a group of genetic diseases known as ciliopathies. More than 20 of these disorders have been identified, and they are characterized by developmental defects causing blindness, deafness, chronic respiratory infections, kidney disease, heart disease, infertility, obesity, diabetes, polydactyly and situs inversus among others. Ciliopathies result from defects in cilia, including the primary cilia projecting into nephron lumens. Primary cilia act as cellular antennae, orchestrating cellular signaling and orienting cells through PCP. We are interested in the role of PCP and primary cilia in shaping nephric tubules.
Current interests in the lab include:
1) Determining how PCP components affect tubule and cilia formation
2) Discovering novel components affecting nephron development
3) Visualizing in vivo tube formation using advanced live imaging techniques
4) Generating transgenic animals to visualize nephrogenesis in vivo
Non-Zebrafish Publications
Chang DR, Alanis DM, Miller RK, Akiyama H, McCrea PD, Chen J. Lung epithelial branching program antagonizes alveolar differentiation. PNAS. 2013 Sep 20. [Epub ahead of print]. *Cover Article
Miller RK. The Xenopus pronephros: Leaps and bounds toward understanding kidney Development. Xenopus Development. Editors: M. Kloc and J. Z. Kubiak. In Press, 2013.
Miller RK, Hong JY, Munoz WA, McCrea PD. The other catenins: challenging our current view of canonical Wnt signaling. Molecular biology of the cadherin and catenin superfamilies, Editor: Frans van Roy. Series: Progress in Molecular Biology and Translational Science, Editor-in-Chief: P. Michael Conn. 2013;116:387-407.
*Calendar Image: Miller RK and Petersen J. Crepidula fornicata (slipper limpet) embryo. Development Journal Calendar (The Company of Biologists). 2013 (January).
*Online Video: Petersen J and Miller RK. Drosophila Tracheal Development. Collaborative Resources for Learning Developmental Biology. http://www.sdbcore.org/object?ObjectID=347&SubTopicID=17. 2012.
Valls G, Codina M, Miller RK, Del Valle B, McCrea PD, de Herreros AG, Dunach M. p120-catenin acts as a Rac1 & Vav2 anchor protein and is required for Rac activation upon Wnt stimulation. J Cell Sci. 2012 Sep 3.
Hong JY, Park JI, Lee M, Munoz WA, Miller RK, Ji H, Gu D, Sokol SY, McCrea PD. Down-syndrome related kinase Dyrk1A modulates the p120-catenin/ Kaiso trajectory of the Wnt signaling pathway. J Cell Sci. 2012 Feb 1;125(Pt 3):561-9. (w/ Journal Highlight)
Miller RK, Gomez de la Torre Canny S, Jang CW, Cho K, Ji H, Wagner DS, Jones EA, Habas R, McCrea PD. Pronephric Tubulogenesis Requires Daam1-Mediated Planar Cell Polarity Signaling. J Am Soc Nephrol. 2011 Sep;22(9):1654-64. (w/ Journal Highlight)
*Cover Image: Miller RK. Embryonic Xenopus laevis kidney. J Am Soc Nephrol. 2011 Sep;22(9).
*Editorial: Hukriede NA and Dawid IB. Making a Tubule the Noncanonical Way. J Am Soc Nephrol. 2011 Sep;22(9):1575-7.
Miller RK and McCrea PD. Wnt to Build a Tube: Contributions of Wnt signaling to epithelial tubulogenesis. Dev Dyn. 2010 Jan;239(1):77-93.
Miller RK, Qadota H, Stark T, Mercer KB, Stevenson T, Anyanful A, Benian GM. CSN-5, a Component of the COP-9 Signalosome Complex, Regulates the Levels of UNC-96 and UNC-98, two components of M-lines in C. elegans Muscle. Mol Biol Cell. 2009 Aug;20(15):3608-16.
Lyons JP, Miller RK, Zhou X, Weidinger G, Deroo T, Denayer T, Park JI, Ji H, Hong JY, Li A, Moon RT, Jones EA, Vleminckx K, Vize PD, McCrea PD. Requirement of Wnt/beta-catenin signaling in pronephric kidney development. Mech Dev. 2009 Mar-Apr;126(3-4):142-59.
Miller RK, Mercer KB, Qadota H, Stark TJ, Benian GM. UNC-98 and UNC-96 interact with paramyosin to promote its incorporation into thick filaments in C. elegans. Mol Biol Cell. 2008 Apr;19(4):1529-39.
Qadota H, Mercer KB, Miller RK, Kaibuchi K, Benian GM. Two LIM Domain Proteins and UNC-96 Link UNC-97/PINCH to Myosin Thick Filaments in Caenorhabditis elegans Muscle. Mol Biol Cell. 2007 Nov;18(11):4317-26.
Miller RK, Qadota H, Landsverk ML, Mercer KB, Epstein HF, Benian GM. UNC-98 is crucial for a molecular connection between muscle focal adhesions and thick filaments in C. elegans. J Cell Bio. 2006 Dec 18;175(6):853-9.
Mercer KB, Miller RK, Tinley TL, Sheth S, Qadota H, Benian GM. Caenorhabditis elegans UNC-96 is a new component of M-Lines that interacts with UNC-98 and paramyosin and is required in adult muscle for assembly and/or maintenance of thick filaments. Mol Biol Cell. 2006 Sep;17(9):3832-47.
Mercer KB, Flaherty DB, Miller RK, Qadota H, Tinley TL, Moerman DG, Benian GM. Caenorhabditis elegans UNC-98, a C2H2 Zn finger protein, is a novel partner of UNC-97/PINCH in muscle adhesion complexes. Mol Biol Cell. 2003 Jun;14(6):2492-507.