Ward, Jordan - University of California, Santa Cruz - Molecular, Cell & Developmental Biology Faculty

个人简介

B. S., University of Alberta M. S., University of Alberta Ph.D., Cancer Research UK, Clare Hall Laboratories and University of London Postdoctorate, University of California, San Francisco

研究领域

The Ward lab is interested in how the remarkable complexity and noise of gene regulation is converted into the beautiful and precise cellular behaviors that drive animal development. Understanding how a genomic blueprint is read by transcription factors to control gene regulatory programs is challenging in animals due to the complexity of tissues and the often-long distances between transcription factor binding sites and regulated genes. We use the nematode C. elegans as a model organism to approach this problem. In addition to its powerful genetics, simple tissues, transparency, and invariant cell lineage, C. elegans has an incredibly compact genome, which makes linking transcription factor binding to cognate gene regulation quite straightforward. We use a combination of genetics, molecular biology, microscopy, in vitro biochemistry, and genomics to determine how individual, evolutionarily conserved transcription factors regulate distinct gene expression programs controlling cell division and differentiation and organ development in living animals. We are especially interested in transcription factor regulation of two cellular processes: i) development of the nematode vulva, which is a paradigm of organogenesis; and ii) the nematode molt, which is the shedding of the old skin (cuticle) and generation of a new one. Molting is an essential process required for growth in any organism with an exoskeleton, and in nematodes involves a striking orchestration of asymmetric cell division, cell migrations and fusions, protease inhibition and release, signaling, extracellular matrix remodeling, and stereotyped behaviors. We also extend our findings into the human parasitic nematode Brugia malayi, which causes the disfiguring disease lymphatic filariasis, in an effort to understand how the gene regulatory networks evolve in the context of a parasitic life cycle. We are also motivated by the public health implications of this work: parasitic nematodes infect over 1.5 billion people globally and also threaten food availability by infecting crops and livestock. As there are only a small number of drugs currently available to fight parasitic nematode infections (ie. lymphatic filariasis, ascariasis, strongyloidiasis), novel approaches are desperately needed. Molting is a particularly good target as it is essential, involves nematode-specific molecules, and is regulated by many druggable targets (proteases, nuclear hormone receptors, etc.). By characterizing key developmental processes in parasites, we aim to develop new approaches to combat helminthic infections.

近期论文

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Spotlight on CRISPR in Strongyloides Parasitic Nematodes. Ward JD. Trends in parasitology. 2018; 34(1):6-9. NIHMSID: NIHMS921774 Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations. Ratnappan R, Ward JD, Yamamoto KR, Ghazi A. Worm. 2016; 5(1):e1151609. The auxin-inducible degradation (AID) system enables versatile conditional protein depletion in C. elegans. Zhang L, Ward JD, Cheng Z, Dernburg AF. Development (Cambridge, England). 2015; 142(24):4374-84. Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes. Ward JD. Genetics. 2015; 201(4):1279-94. Rad51 Paralogs Remodel Pre-synaptic Rad51 Filaments to Stimulate Homologous Recombination. Taylor MRG, Špírek M, Chaurasiya KR, Ward JD, Carzaniga R, Yu X, Egelman EH, Collinson LM, Rueda D, Krejci L, Boulton SJ. Rapid and precise engineering of the Caenorhabditis elegans genome with lethal mutation co-conversion and inactivation of NHEJ repair. Ward JD. Genetics. 2015; 199(2):363-77. Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans. Ratnappan R, Amrit FR, Chen SW, Gill H, Holden K, Ward J, Yamamoto KR, Olsen CP, Ghazi A. PLoS genetics. 2014; 10(12):e1004829. SUMO as a nuclear hormone receptor effector: New insights into combinatorial transcriptional regulation. Ward JD, Yamamoto KR, Asahina M. Worm. 2014; 3:e29317.