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One of the major focuses of my laboratory is to develop both forward and reverse genetic tools in zebrafish. Currently, we routinely utilize transposon, recombinase, TALEN and CRISPR/Cas9 systems for genome engineering. I have broad training in molecular, cell and developmental biology and more than 25 years of experience working with zebrafish, first as a graduate student and later as a postdoctoral researcher and research associate. Since my initial exposure to zebrafish, I have had a passion for the beauty of the optically clear embryos that allow detailed examination of development and the powerful genetic opportunities of the system. As a research associate at the Huntsman Cancer Institute, I was trained in cardiovascular biology with a focus on understanding the mechanisms of left-right asymmetry in development. Since 2002, I have focused my efforts on identifying novel anti-angiogenesis mechanisms. As the Scientific Director at Discovery Genomics, Inc., I led and conducted morpholino-based screens in zebrafish to identify novel genes required for angiogenesis and innate immunity. As the PI of my laboratory at Iowa State University, I have further examined the identified genes using small molecule screens in zebrafish embryos. My laboratory has developed several transgenic models in zebrafish to follow endothelial tube formation in living embryos.
More recently, my laboratory has been a part of developing transformative methodologies to mutate and knockout genes in zebrafish that are broadly applicable to other organisms. I have over the last 12 years developed methodologies for forward and reverse genetic approaches in zebrafish. Using TALENs and CRISPR/Cas9, we made over 20 mutants in vascular associated genes by creating short insertions or deletions (indels). Only one of these mutants had a vascular phenotype (ve-cadherin) despite having obvious vascular phenotypes with Morpholinos. This difference in many cases is likely due to compensation of the indel mutations. To address this issue, my laboratory has developed efficient methods to create site-directed integrations using CRISPR/Cas9 to produce strong loss of function phenotypes that can be easily followed with fluorescence (see preliminary data and reference below and in progress report). We think this novel approach will serve to generate reproducible data, bring clarity to our work and enlighten the community to the differences observed between morpholino and indel mutations. We have recently submitted this manuscript to BioRxiv as this paper moves through review:
Wesley A. Wierson, Jordan M. Welker, Maira P. Almeida, Carla M. Mann, Dennis A,
Webster, Trevor J. Weiss, Melanie E. Torrie, Macy K. Vollbrecht, Merrina Lan, Kenna C.
McKeighan, Zhitao Ming, Alec Wehmeier, Christopher S. Mikelson, Jeffrey A. Haltom,
Kristen M. Kwan, Chi-Bin Chien, Darius Balciunas, Stephen C. Ekker, Karl J. Clark, Beau R.
Webber, Branden Moriarity, Staci L. Solin, Daniel F. Carlson, Drena L. Dobbs, Maura
McGrail, Jeffrey J. Essner*. GeneWeld: a method for efficient targeted integration directed by short homology. Oct. 3, 2018; doi: http://dx.doi.org/10.1101/431627.
Commitment to training the next generation of scientists: As Scientific Director of a small biotech company and as PI of my laboratory at ISU, I have directly supervised and trained 4 PhD and 2 MS graduate students. I currently mentor 2 PhD students on vascular and cancer-related projects. I have also served on over 40 Program of Study Committees for graduate students and was the head of our Genetics and Genomics Graduate Program at ISU.
As part of a HHMI education grant, I transformed our Developmental Biology Laboratory class into an inquiry-based research experience using gene editing and zebrafish. Undergraduate students spend the semester designing and producing gRNAs for targeted integration in zebrafish, as presented in our progress report. This currently trains 60 undergraduates per semester in gene editing and developmental genetics.
Research Interests
Papers共 70 篇Author StatisticsCo-AuthorSimilar Experts
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Renu Srivastava, Connor W. Davison, Abigail G. Krull, Seth M. Entriken, Amanda Zumbrock, Maria Daniela Cortes Hidalgo, Kiernan J. Adair, Anna M. Escherich, Jonathan N. Lara, Emma C. Neverman, Megan Hodnefield, Elyse Mcelligtot,
ZEBRAFISHno. 2 (2024): 162-170
Connor Davison, Hamelynn Harzman, Jessie Nicholson, Seth Entriken, Kierinn Mobley, Abigail Krull, Manik Singhal, Caleb Skow, Nathan Matthews, Lindsey Kopp, Benjamin Gillette, Tyler J. Weide,
ZEBRAFISHno. 2 (2024): 191-197
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eLife (2021)
Bio-protocolno. 14 (2021): e4100-e4100
Maira P. Almeida,Jordan M. Welker, Sahiba Siddiqui, Jon Luiken,Stephen C. Ekker,Karl J. Clark,Jeffrey J. Essner,Maura McGrail
Scientific Reportsno. 1 (2021): 1732-12
crossref(2020)
Noriko Ichino,MaKayla R Serres,Rhianna M Urban,Mark D Urban,Anthony J Treichel,Kyle J Schaefbauer, Lauren E Greif,Gaurav K Varshney, Kimberly J Skuster,Melissa S McNulty,Camden L Daby,Ying Wang,
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