The National Institute of Diabetes & Digestive & Kidney Diseases

Oocytes in most organisms are fertilized prior to the completion of the meiotic divisions. Hence, the execution of these divisions is the first developmental event that the embryo must accomplish. The proper segregation of the oocyte chromosomes into polar bodies and the formation of a haploid maternal pronucleus are absolutely essential for normal development of all animals. Any errors in the first or second meiotic division will cause abnormal chromosome segregation, leading to aneuploidy and embryonic lethality, which are the causes of most spontaneous miscarriages in humans. These defects are also responsible for trisomy syndromes such as Down syndrome.

My laboratory is interested in understanding the molecular mechanisms that are at work to regulate the meiotic divisions. We have been studying the maternal factors that control and regulate this process. Our new focus is to understand the role that paternal factors may play in the oocyte meiotic divisions. The SPE-11 protein is the only factor known in C. elegans to be specifically donated to the embryo via the sperm. Please read more about this project in Ongoing Projects.

The other main focus of the lab is studying the C. elegans orthologs of genes, that when mutated, are known to cause disease in humans. This is a new project for us. We believe that by performing genetic suppressor screens with C. elegans mutants we will be able to learn more about the mechanism of action of a given gene. This knowledge should help further our understanding of the function of this gene in humans. We also believe that some of our suppressors could end up being potential therapeutic targets for the human disease. Please read more about our strategies in Ongoing Projects section.

Shakes DC, Allen AK, Albert KM, Golden A. emb-1 encodes the APC16 subunit of the Caenorhabditis elegansAnaphase-Promoting ComplexGenetics (189):549-560, 2011. [Full Text/Abstract]

Richie CT, Bembenek JN, Chestnut B, Furuta T, Schumacher JM, Wallenfang M, Golden A. Protein phosphatase 5 is a negative regulator of separase function during cortical granule exocytosis in C. elegansJ Cell Sci (124):2903-13, 2011. [Full Text/Abstract]

Stein KK, Nesmith JE, Ross BD, Golden A. Functional redundancy of paralogs of an anaphase promoting complex/cyclosome subunit in Caenorhabditis elegans meiosis. Genetics (186):1285-93, 2010. [Full Text/Abstract]

Golden A, Liu J, Cohen-Fix O. Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope. J Cell Sci. (122):1970-8, 2009. [ Full Text/Abstract]

Arur S, Ohmachi M, Nayak S, Hayes M, Miranda A, Hay A, Golden A, Schedl T. Multiple ERK substrates execute single biological processes in Caenorhabditis elegans germ-line development.Proc Natl Acad Sci U S A. (106): 4776-81, 2009. [Full Text/Abstract]

Stein KK, Davis ES, Hays T, Golden A Components of the spindle assembly checkpoint regulate the anaphase-promoting complex during meiosis in Caenorhabditis elegans. Genetics(175): 107-23, 2007. [Full Text/Abstract]

Bembenek JN, Richie CT, Squirrell JM, Campbell JM, Eliceiri KW, Poteryaev D, Spang A, Golden A, White JG Cortical granule exocytosis in C. elegans is regulated by cell cycle components including separase. Development(134): 3837-3848, 2007. [Full Text/Abstract]

Golden A, O''Connell KF Silence is golden: combining RNAi and live cell imaging to study cell cycle regulatory genes during Caenorhabditis elegans development. Methods(41): 190-7, 2007. [Full Text/Abstract]

Burrows AE, Sceurman BK, Kosinski ME, Richie CT, Sadler PL, Schumacher JM, Golden A The C. elegans Myt1 ortholog is required for the proper timing of oocyte maturation. Development (133): 697-709, 2006. [Full Text/Abstract]

Richie CT, Golden A Chromosome segregation: Aurora B gets Tousled. Curr Biol (15): R379-82, 2005. [Full Text/Abstract]

Shakes DC Sadler PL Schumacher JM Abdolrasulnia M Golden A Developmental defects observed in hypomorphic anaphase-promoting complex mutants are linked to cell cycle abnormalities. Development (130): 1605-20, 2003. [Full Text/Abstract]

Golden A Cohen-Fix O Getting (chromosomes) loaded--a new role for timeless. Dev Cell (5): 7-9, 2003. [Full Text/Abstract]

Ashcroft N Golden A CDC-25.1 regulates germline proliferation in Caenorhabditis elegans. Genesis (33): 1-7, 2002. [Full Text/Abstract]

Davis ES Wille L Chestnut BA Sadler PL Shakes DC Golden A Multiple subunits of the Caenorhabditis elegans anaphase-promoting complex are required for chromosome segregation during meiosis I. Genetics (160): 805-13, 2002. [Full Text/Abstract]

Morton DG Shakes DC Nugent S Dichoso D Wang W Golden A Kemphues KJ The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo. Dev Biol (241): 47-58, 2002. [Full Text/Abstract]

Chase D Golden A Heidecker G Ferris DK Caenorhabditis elegans contains a third polo-like kinase gene. DNA Seq (11): 327-34, 2000. [Full Text/Abstract]

Golden A Cytoplasmic flow and the establishment of polarity in C. elegans 1-cell embryos. Curr Opin Genet Dev (10): 414-20, 2000. [Full Text/Abstract]

Golden A Sadler PL Wallenfang MR Schumacher JM Hamill DR Bates G Bowerman B Seydoux G Shakes DC Metaphase to anaphase (mat) transition-defective mutants in Caenorhabditis elegans. J Cell Biol (151): 1469-82, 2000. [Full Text/Abstract]

Chase D Serafinas C Ashcroft N Kosinski M Longo D Ferris DK Golden A The polo-like kinase PLK-1 is required for nuclear envelope breakdown and the completion of meiosis in Caenorhabditis elegans. Genesis (26): 26-41, 2000. [Full Text/Abstract]

Wilson MA Hoch RV Ashcroft NR Kosinski ME Golden A A Caenorhabditis elegans wee1 homolog is expressed in a temporally and spatially restricted pattern during embryonic development. Biochim Biophys Acta (1445): 99-109, 1999. [Full Text/Abstract]

Ashcroft NR Srayko M Kosinski ME Mains PE Golden A RNA-Mediated interference of a cdc25 homolog in Caenorhabditis elegans results in defects in the embryonic cortical membrane, meiosis, and mitosis. Dev Biol (206): 15-32, 1999. [Full Text/Abstract]

Schumacher JM Ashcroft N Donovan PJ Golden A A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development (125): 4391-402, 1998. [Full Text/Abstract]

Schumacher JM Golden A Donovan PJ AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell Biol (143): 1635-46, 1998. [Full Text/Abstract]

Ashcroft NR Kosinski ME Wickramasinghe D Donovan PJ Golden A The four cdc25 genes from the nematode Caenorhabditis elegans. Gene (214): 59-66, 1998. [Full Text/Abstract]

Sternberg PW Yoon CH Lee J Jongeward GD Kayne PS Katz WS Lesa G Liu J Golden A Huang LS et al Molecular genetics of proto-oncogenes and candidate tumor suppressors in Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol (59): 155-63, 1994. [Full Text/Abstract]

Han M Golden A Han Y Sternberg PW C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval differentiation. Nature (363): 133-40, 1993. [Full Text/Abstract]

Sternberg PW Golden A Han M Role of a raf proto-oncogene during Caenorhabditis elegans vulval development. Philos Trans R Soc Lond B Biol Sci (340): 259-65, 1993. [Full Text/Abstract]