Ph.D. (2000) University of Wisconsin-Madison
Postdoctoral Research: HHMI, UC-Berkeley, 2000-2004
Lab website: http://skoplab.weebly.com/
Address: 2426 Genetics/Biotech
Investigating the mechanisms that regulate asymmetric cell division
Genomics & Proteomics
Human, mouse & rat
Asymmetric cell division ultimately determines the cellular identity of
each cell in a multicellular organism. The establishment of cell
asymmetry is controlled by two mechanisms: first, the cell must polarize
cell fate determinants; second, the mitotic spindle must be aligned
with the axis of polarity. Following the asymmetric distribution of cell
fate determinants, the cell undergoes cytokinesis, producing two
daughter cells of different cell fates. Errors in these events often
lead to genetic instability and abnormal cell behavior as seen in breast
cancer, a variety of birth defects and age-related disorders, for
example. The membrane cortex, a region of the cell that includes the
plasma membrane and the dense cytoskeleton just beneath, plays a central
role in cell asymmetry, yet we know very little about how it is
regulated and maintained during embryonic development.
My research program examines the mechanisms that regulate asymmetric cell division. My ultimate goal is to understand how membrane trafficking events contribute to cell asymmetry and cytokinesis. The work in my lab integrates several approaches from genetics, cell biology, genomics and proteomics accompanied with high resolution in vivo microscopy to accomplish these goals. I use a combination of C. elegans and Chinese Hamster Ovary (CHO) cells to dissect the mechanisms that regulate asymmetric cell division during embryonic development. Over the past few year years, my research group examined (i) the role of membrane trafficking in maintaining anterior PAR polarity, (ii) the role of RACK-1 in cytokinesis and polarity, and (iii) sequenced the proteome of the mammalian (CHO cell) metaphase spindle. Our findings suggest that membrane trafficking and remodeling is tightly coordinated and maintained throughout the cell cycle to ensure proper cell asymmetry and division during embryonic development. Our immediate future goals are to gain an understanding of the molecular pathways that regulate membrane trafficking during cell asymmetry and cytokinesis.
Pittmann, KJ & Skop, AR (2012). Anterior PAR proteins function
during cytokinesis and maintain DYN-1 at the cleavage furrow in
Caenorhabditis elegans. Cytoskeleton. Aug 6 2012 doi: 10.1002/cm.21053
[Epub ahead of print] PMID: 22887994
Shivas, JM & Skop, AR (2012). C. elegans Arp2/3 mediates early endosomal dynamics and recycling of anterior polarity cues to promote PAR maintenance. MBoC. 2012 Mar 28. [Epub ahead of print] PMID: 22456506
Bonner MK, Poole DS, Xu T, Sarkeshik A, Yates III JR, Skop AR (2011). Mitotic spindle proteomics in Chinese Hamster Ovary cells. PLoS ONE 6(5): e20489. doi:10.1371/journal.pone.0020489
Ai E, Poole DS, Skop AR (2011). Long astral microtubules and RACK-1 stabilize polarity domains during maintenance phase in Caenorhabditis elegans embryos. PLoS ONE 6(4): e19020.
Shivas JM*, Morrison HA*, Bilder D, Skop AR (2010). Polarity and endocytosis: reciprocal regulation. Trends in Cell Biology. 20(8): 445-52. *authors contributed equallyAi E, Skop AR (2009). Endosomal recycling regulation during cytokinesis. Communicative & Integrative Biology. 2(5): 444-7.
Nakayama Y*, Shivas JM*, Poole DS, Squirrell JM, Kulkoski JM, Schleede JB, Skop AR. (2009). Dynamin participates in the maintenance of anterior polarity in the Caenorhabditis elegans embryo. Developmental Cell. Jun; 16(6): 889-900.
Ai E, Poole DS, Skop AR (2009). RACK-1 directs dynactin-dependent RAB-11 endosomal recycling during mitosis in Caenorhabditis elegans. Molecular Biology of the Cell. Mar; 20(6): 1629-38.
Bonner MK, Skop AR (2008). Cell division screens and dynamin. Biochemical Society Transactions. Jun; 36(Pt 3): 431-5.
Zhang H, Skop AR, White JG (2008). Src and Wnt signaling regulate dynactin accumulation to the P2-EMS cell border in C. elegans embryos. Journal of Cell Science. Jan 15; 121(Pt 2): 155-61.
Dinkelmann MV, Zhang H, Skop AR, White JG (2007). SPD-3 is required for spindle alignment in Caenorhabditis elegans embryos and localizes to mitochondria. Genetics. Nov; 177(3): 1609-20.
Konopka CA, Schleede JB, Skop AR, Bednarek SY (2006). Dynamin and cytokinesis. Traffic. Mar; 7(3): 239-47.
Otegui MS, Verbrugghe KJ, Skop AR (2005). Midbodies and phragmoplasts: analogous structures involved in cytokinesis. Trends in Cell Biology. Aug; 15(8): 404-13.
Skop AR, Liu H, Yates J 3rd, Meyer BJ, Heald R (2004). Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science. Jul 2; 305(5680): 61-6.
Thompson HM*, Skop AR*, Euteneuer U, Meyer BJ, McNiven MA (2002). The large GTPase dynamin associates with the spindle midzone and is required for cytokinesis. Current Biology. Dec 23; 12(24): 2111-7. *authors contributed equally
Skop AR, Bergmann D, Mohler WA, White JG (2001). Completion of cytokinesis in C. elegans requires a brefeldin A-sensitive membrane accumulation at the cleavage furrow apex. Current Biology. May 15; 11(10): 735-46.