Fabio Piano

Genomics, genetics and evolution of early C. elegans development

We study the genetic and evolutionary mechanisms underlying early embryonic development using a combination of molecular genetic and functional genomics approaches in the animal model C. elegans and related nematodes. One of the main tools we have used is RNA interference (RNAi) followed by time-lapse microscopy to work toward a comprehensive molecular description of early embryogenesis in C. elegans. RNAi offers a powerful way to obtain information about the loss-of-function phenotype of the genes tested, while the early embryo offers a system in which basic cellular and developmental processes can be easily studied. 

In collaboration with several other labs, we developed the first genome-wide RNAi inventory of genes required for the first few cell divisions in any animal. By clustering genes based on their phenotypic profiles, we identified groups of genes required for basic processes such as nuclear movements, mitotic spindle formation, cytokinesis, cell cycle progression, and proper asymmetric cell division. These data provided a starting point to study the molecular architecture of specific cellular processes. Most of the genes identified are conserved in humans, and many of their human homologs are associated with genetic diseases, including some that have been previously targeted for anti-cancer drug development. Therefore, our data can be used not only to analyze the C. elegans genome but also to guide the functional examination of the human genome. 

Since only around 15% of genes show any phenotype when knocked down on their own, we have extended this work to generate genome-wide genetic interaction maps for essential genes that play important roles in the early embryo. By analyzing the genetic interaction data in combination with other kinds of functional analyses, we are learning how animals coordinate different cellular processes during development. This work will help us understand genetic diseases, most of which are not Mendelian (due to defects in a single gene), but instead arise from interactions between alleles in multiple genes.

We also study the evolution of developmental mechanisms. Comparisons across different nematode species have revealed fundamental differences in modes of reproduction and in developmental patterning. Significantly, in some species the wild-type patterns of early embryonic cell divisions resemble those produced by various C. elegans mutants, indicating plasticity in the underlying molecular networks. We have recently sequenced the genome of a parthogenetic relative of C. elegans that shows an alternate pattern of early cleavages. Strikingly, this species also appears to have a single giant chromosome derived from fusion of six or seven ancestral chromosomes. We are examining these phenotypic differences in conjunction with molecular analyses to identify mechanisms underlying the phenotypic diversity seen in nature.

Post-doctoral fellowship from the Damon Runyon-Walter Winchell Foundation for Cancer Research

The Gladys Mateyko Award for Excellence in Biology

The James Arthur Fellowship

Date of these PubMed search results: March 24 2020
Get the current Pubmed search results

1. Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment.
   PLoS Genet (2019 Feb) PMC6383947 free full-text archive
   Bezler A, Braukmann F, West SM, Duplan A, Conconi R, Schutz F, Gonczy P, Piano F, Gunsalus K, Miska EA, Keller L
2. Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis.
   Dev Cell (2019 Mar 25) PMC6436959 free full-text archive
   Beltran T, Barroso C, Birkle TY, Stevens L, Schwartz HT, Sternberg PW, Fradin H, Gunsalus K, Piano F, Sharma G, Cerrato C, Ahringer J, Martinez‑Perez E, Blaxter M, Sarkies P
3. Developmental dynamics of gene expression and alternative polyadenylation in the Caenorhabditis elegans germline.
   Genome Biol (2018 Jan 24) PMC5784609 free full-text archive
   West SM, Mecenas D, Gutwein M, Aristizabal‑Corrales D, Piano F, Gunsalus KC
4. Genome Architecture and Evolution of a Unichromosomal Asexual Nematode.
   Curr Biol (2017 Oct 9) PMC5659720 free full-text archive
   Fradin H, Kiontke K, Zegar C, Gutwein M, Lucas J, Kovtun M, Corcoran DL, Baugh LR, Fitch DHA, Piano F, Gunsalus KC
5. A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans.
   Development (2016 Oct 1) PMC5087616 free full-text archive
   Weicksel SE, Mahadav A, Moyle M, Cipriani PG, Kudron M, Pincus Z, Bahmanyar S, Abriola L, Merkel J, Gutwein M, Fernandez AG, Piano F, Gunsalus KC, Reinke V
6. Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation.
   PLoS Genet (2016 Jun) PMC4920428 free full-text archive
   Gomez‑Saldivar G, Fernandez A, Hirano Y, Mauro M, Lai A, Ayuso C, Haraguchi T, Hiraoka Y, Piano F, Askjaer P
7. In Vivo Interaction Proteomics in Caenorhabditis elegans Embryos Provides New Insights into P Granule Dynamics.
   Mol Cell Proteomics (2016 May) PMC4858945 free full-text archive
   Chen JX, Cipriani PG, Mecenas D, Polanowska J, Piano F, Gunsalus KC, Selbach M
8. Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.
   Elife (2015 Aug 22) PMC4569889 free full-text archive
   Paaby AB, White AG, Riccardi DD, Gunsalus KC, Piano F, Rockman MV
9. Comparative validation of the D. melanogaster modENCODE transcriptome annotation.
   Genome Res (2014 Jul) PMC4079975 free full-text archive
   Chen ZX, Sturgill D, Qu J, Jiang H, Park S, Boley N, Suzuki AM, Fletcher AR, Plachetzki DC, FitzGerald PC, Artieri CG, Atallah J, Barmina O, Brown JB, Blankenburg KP, Clough E, Dasgupta A, Gubbala S, Han Y, Jayaseelan JC, Kalra D, Kim YA, Kovar CL, Lee SL, Li M, Malley JD, Malone JH, Mathew T, Mattiuzzo NR, Munidasa M, Muzny DM, Ongeri F, Perales L, Przytycka TM, Pu LL, Robinson G, Thornton RL, Saada N, Scherer SE, Smith HE, Vinson C, Warner CB, Worley KC, Wu YQ, Zou X, Cherbas P, Kellis M, Eisen MB, Piano F, Kionte K, Fitch DH, Sternberg PW, Cutter AD, Duff MO, Hoskins RA, Graveley BR, Gibbs RA, Bickel PJ, Kopp A, Carninci P, Celniker SE, Oliver B, Richards S
10. Global characterization of the oocyte-to-embryo transition in Caenorhabditis elegans uncovers a novel mRNA clearance mechanism.
    EMBO J (2014 Aug 18) PMC4195759 free full-text archive
    Stoeckius M, Grun D, Kirchner M, Ayoub S, Torti F, Piano F, Herzog M, Selbach M, Rajewsky N
11. Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans.
    G3 (Bethesda) (2014 Jan 10) PMC3887534 free full-text archive
    Fernandez AG, Mis EK, Lai A, Mauro M, Quental A, Bock C, Piano F
12. A compendium of RNA-binding motifs for decoding gene regulation.
    Nature (2013 Jul 11) PMC3929597 free full-text archive
    Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D, Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR
13. DevStaR: high-throughput quantification of C. elegans developmental stages.
    IEEE Trans Med Imaging (2013 Oct) PMID: 23722463
    White AG, Lees B, Kao HL, Cipriani PG, Munarriz E, Paaby AB, Erickson K, Guzman S, Rattanakorn K, Sontag E, Geiger D, Gunsalus KC, Piano F
14. High-throughput fluorescence-based isolation of live C. elegans larvae.
    Nat Protoc (2012 Jul 19) PMC5274720 free full-text archive
    Fernandez AG, Bargmann BO, Mis EK, Edgley ML, Birnbaum KD, Piano F
15. RNAi methods and screening: RNAi based high-throughput genetic interaction screening.
    Methods Cell Biol (2011) PMID: 22118275
    Cipriani PG, Piano F
16. A model of cytoplasmically driven microtubule-based motion in the single-celled Caenorhabditis elegans embryo.
    Proc Natl Acad Sci U S A (2011 Jun 28) PMC3127902 free full-text archive
    Shinar T, Mana M, Piano F, Shelley MJ
17. A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue.
    Cell (2011 Apr 29) PMC3086541 free full-text archive
    Green RA, Kao HL, Audhya A, Arur S, Mayers JR, Fridolfsson HN, Schulman M, Schloissnig S, Niessen S, Laband K, Wang S, Starr DA, Hyman AA, Schedl T, Desai A, Piano F, Gunsalus KC, Oegema K
18. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project.
    Science (2010 Dec 24) PMC3142569 free full-text archive
    Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska‑Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM 3rd, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH
19. Rapid and accurate developmental stage recognition of C. elegans from high-throughput image data.
    Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit (2010 Aug 5) PMC3205469 free full-text archive
    White AG, Cipriani PG, Kao HL, Lees B, Geiger D, Sontag E, Gunsalus KC, Piano F
20. The landscape of C. elegans 3'UTRs.
    Science (2010 Jul 23) PMC3142571 free full-text archive
    Mangone M, Manoharan AP, Thierry‑Mieg D, Thierry‑Mieg J, Han T, Mackowiak SD, Mis E, Zegar C, Gutwein MR, Khivansara V, Attie O, Chen K, Salehi‑Ashtiani K, Vidal M, Harkins TT, Bouffard P, Suzuki Y, Sugano S, Kohara Y, Rajewsky N, Piano F, Gunsalus KC, Kim JK
21. Automated sorting of live C. elegans using laFACS.
    Nat Methods (2010 Jun) PMC2896029 free full-text archive
    Fernandez AG, Mis EK, Bargmann BO, Birnbaum KD, Piano F
22. EGG-4 and EGG-5 Link Events of the Oocyte-to-Embryo Transition with Meiotic Progression in C. elegans.
    Curr Biol (2009 Nov 3) PMC2783797 free full-text archive
    Parry JM, Velarde NV, Lefkovith AJ, Zegarek MH, Hang JS, Ohm J, Klancer R, Maruyama R, Druzhinina MK, Grant BD, Piano F, Singson A
23. Large-scale sorting of C. elegans embryos reveals the dynamics of small RNA expression.
    Nat Methods (2009 Oct) PMC2756031 free full-text archive
    Stoeckius M, Maaskola J, Colombo T, Rahn HP, Friedlander MR, Li N, Chen W, Piano F, Rajewsky N
24. Evolution of early embryogenesis in rhabditid nematodes.
    Dev Biol (2009 Nov 1) PMC2763944 free full-text archive
    Brauchle M, Kiontke K, MacMenamin P, Fitch DH, Piano F
25. Unlocking the secrets of the genome.
    Nature (2009 Jun 18) PMC2843545 free full-text archive
    Celniker SE, Dillon LA, Gerstein MB, Gunsalus KC, Henikoff S, Karpen GH, Kellis M, Lai EC, Lieb JD, MacAlpine DM, Micklem G, Piano F, Snyder M, Stein L, White KP, Waterston RH
26. A protein domain-based interactome network for C. elegans early embryogenesis.
    Cell (2008 Aug 8) PMC2596478 free full-text archive
    Boxem M, Maliga Z, Klitgord N, Li N, Lemmens I, Mana M, de Lichtervelde L, Mul JD, van de Peut D, Devos M, Simonis N, Yildirim MA, Cokol M, Kao HL, de Smet AS, Wang H, Schlaitz AL, Hao T, Milstein S, Fan C, Tipsword M, Drew K, Galli M, Rhrissorrakrai K, Drechsel D, Koller D, Roth FP, Iakoucheva LM, Dunker AK, Bonneau R, Gunsalus KC, Hill DE, Piano F, Tavernier J, van den Heuvel S, Hyman AA, Vidal M
27. Diverse roles of actin in C. elegans early embryogenesis.
    BMC Dev Biol (2007 Dec 24) PMC2323969 free full-text archive
    Velarde N, Gunsalus KC, Piano F
28. C. elegans network biology: a beginning.
    WormBook (2006 Aug 21) PMC4781290 free full-text archive
    Piano F, Gunsalus KC, Hill DE, Vidal M
29. UTRome.org: a platform for 3'UTR biology in C. elegans.
    Nucleic Acids Res (2008 Jan) PMC2238901 free full-text archive
    Mangone M, Macmenamin P, Zegar C, Piano F, Gunsalus KC
30. EGG-3 regulates cell-surface and cortex rearrangements during egg activation in Caenorhabditis elegans.
    Curr Biol (2007 Sep 18) PMID: 17869112
    Maruyama R, Velarde NV, Klancer R, Gordon S, Kadandale P, Parry JM, Hang JS, Rubin J, Stewart‑Michaelis A, Schweinsberg P, Grant BD, Piano F, Sugimoto A, Singson A
31. Forward chemical genetic approach identifies new role for GAPDH in insulin signaling.
    Nat Chem Biol (2007 Jan) PMID: 17115034
    Min J, Kyung Kim Y, Cipriani PG, Kang M, Khersonsky SM, Walsh DP, Lee JY, Niessen S, Yates JR 3rd, Gunsalus K, Piano F, Chang YT
32. MEL-28 is downstream of the Ran cycle and is required for nuclear-envelope function and chromatin maintenance.
    Curr Biol (2006 Sep 5) PMID: 16950115
    Fernandez AG, Piano F
33. A peptidomimetic siRNA transfection reagent for highly effective gene silencing.
    Mol Biosyst (2006 Jun) PMID: 16880950
    Utku Y, Dehan E, Ouerfelli O, Piano F, Zuckermann RN, Pagano M, Kirshenbaum K
34. Two phases of astral microtubule activity during cytokinesis in C. elegans embryos.
    Dev Cell (2006 Apr) PMID: 16580995
    Motegi F, Velarde NV, Piano F, Sugimoto A
35. A genome-wide map of conserved microRNA targets in C. elegans.
    Curr Biol (2006 Mar 7) PMID: 16458514
    Lall S, Grun D, Krek A, Chen K, Wang YL, Dewey CN, Sood P, Colombo T, Bray N, Macmenamin P, Kao HL, Gunsalus KC, Pachter L, Piano F, Rajewsky N
36. Nucleoporins NPP-1, NPP-3, NPP-4, NPP-11 and NPP-13 are required for proper spindle orientation in C. elegans.
    Dev Biol (2006 Jan 15) PMC1405919 free full-text archive
    Schetter A, Askjaer P, Piano F, Mattaj I, Kemphues K
37. Caenorhabditis elegans decapping proteins: localization and functional analysis of Dcp1, Dcp2, and DcpS during embryogenesis.
    Mol Biol Cell (2005 Dec) PMC1289429 free full-text archive
    Lall S, Piano F, Davis RE
38. Toward automatic phenotyping of developing embryos from videos.
    IEEE Trans Image Process (2005 Sep) PMID: 16190471
    Ning F, Delhomme D, LeCun Y, Piano F, Bottou L, Barbano PE
39. Predictive models of molecular machines involved in Caenorhabditis elegans early embryogenesis.
    Nature (2005 Aug 11) PMID: 16094371
    Gunsalus KC, Ge H, Schetter AJ, Goldberg DS, Han JD, Hao T, Berriz GF, Bertin N, Huang J, Chuang LS, Li N, Mani R, Hyman AA, Sonnichsen B, Echeverri CJ, Roth FP, Vidal M, Piano F
40. New genes with roles in the C. elegans embryo revealed using RNAi of ovary-enriched ORFeome clones.
    Genome Res (2005 Feb) PMC546526 free full-text archive
    Fernandez AG, Gunsalus KC, Huang J, Chuang LS, Ying N, Liang HL, Tang C, Schetter AJ, Zegar C, Rual JF, Hill DE, Reinke V, Vidal M, Piano F
41. RNAi as a tool to study cell biology: building the genome-phenome bridge.
    Curr Opin Cell Biol (2005 Feb) PMID: 15661512
    Gunsalus KC, Piano F
42. Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss.
    Proc Natl Acad Sci U S A (2004 Jun 15) PMC428462 free full-text archive
    Kiontke K, Gavin NP, Raynes Y, Roehrig C, Piano F, Fitch DH
43. A map of the interactome network of the metazoan C. elegans.
    Science (2004 Jan 23) PMC1698949 free full-text archive
    Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane‑Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette‑Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M
44. RNAiDB and PhenoBlast: web tools for genome-wide phenotypic mapping projects.
    Nucleic Acids Res (2004 Jan 1) PMC308844 free full-text archive
    Gunsalus KC, Yueh WC, MacMenamin P, Piano F
45. mRNA capping enzyme requirement for Caenorhabditis elegans viability.
    J Biol Chem (2003 Apr 18) PMID: 12576475
    Srinivasan P, Piano F, Shatkin AJ
46. Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. elegans.
    Curr Biol (2002 Nov 19) PMID: 12445391
    Piano F, Schetter AJ, Morton DG, Gunsalus KC, Reinke V, Kim SK, Kemphues KJ
47. Integrating interactome, phenome, and transcriptome mapping data for the C. elegans germline.
    Curr Biol (2002 Nov 19) PMID: 12445390
    Walhout AJ, Reboul J, Shtanko O, Bertin N, Vaglio P, Ge H, Lee H, Doucette‑Stamm L, Gunsalus KC, Schetter AJ, Morton DG, Kemphues KJ, Reinke V, Kim SK, Piano F, Vidal M