We are interested in mechanisms of genome maintenance and organization. During interphase, chromosomes are surrounded by the nuclear envelope (NE), separating the nuclear and cytoplasmic compartments of the cell. Exchange of all molecules between the nucleus and the rest of the cell occurs through nuclear pore complexes (NPCs; Figure 1), which are embedded in the NE. NPCs are not only conduits for nucleo-cytoplasmic trafficking, they also promote many aspects of interphase nuclear function, including gene expression and heterochromatin organization. As mammalian cells divide, the NE breaks down and chromosomes condense to allow their partitioning into daughter cells. Remarkably, NPC proteins (nucleoporins) and other components of the nuclear transport machinery have distinct and important mitotic roles that assure the accurate segregation of chromosomes.
Our current focus is to elucidate the role of nucleoporins, NPC–associated proteins (e.g., the SUMO pathway, spindle checkpoint proteins), and other components of the nuclear transport machinery (e.g., the Ran pathway) throughout the cell cycle. We are interested both in how they maintain nuclear organization during interphase and how they promote chromosome segregation. To address both aspects, we have adapted CRISPR–based degron strategies to the study of these proteins; namely, we have tagged the proteins with auxin-induced degrons (AID), which cause them to be specifically destroyed upon the addition of auxin, a plant hormone. The ultimate goals of our studies are to understand how these pathways enable correct genome organization and accurate chromosome segregation, as well as to discover how their functions are coordinated with each other and with other aspects of cell physiology.
Mary Dasso is a Senior Investigator in the Division of Intramural Research, National Institute of Child Health and Human Development (NICHD-DIR). Dr. Dasso received her BA in Chemistry from the Clark Honors College at the University of Oregon. She was awarded a Marshall Scholarship to study at the University of Cambridge. After receiving her PhD in Biochemistry, she was awarded a Damon Runyon Postdoctoral Fellowship to work at the University of California, San Diego. She then moved to the NICHD-DIR, where she continues to lead a highly active research group. Dr. Dasso’s studies focus on non-canonical roles of the nuclear transport machinery. Proteins of the nuclear pore complex (nucleoporins) have been implicated in cellular functions beyond nucleocytoplasmic transport, including chromosome organization, gene expression, cell signaling and cell-cycle control. Understanding the activities of individual nucleoporins has been historically difficult because of their multifaceted nature, abundance, and unusual stability. To overcome these issues, she developed human tissue-culture cells that allow conditional depletions of individual nucleoporins, and used this system to define the mechanisms through which individual nucleoporins contribute to nuclear pore structure, nuclear trafficking, gene expression and development. She is currently investigating tissue-specific roles of nucleoporins, with the hope of understanding how disruption of nucleoporin functions causes genetic diseases and neurodegenerative conditions. Beyond her own laboratory, Dr. Dasso has held Intramural NIH leadership positions, including recent service as the NICHD-DIR Acting Scientific Director. She has received numerous awards in recognition of her accomplishments, including a 2020 NIH Director’s Award and a 2021 NICHD Merit Award, as well as selection as a fellow of the American Society for Cell Biology and the American Association for the Advancement of Science.
- Chen S, Lyanguzova M, Kaufhold R, Plevock Haase KM, Lee H, Arnaoutov A, Dasso M. Association of RanGAP to nuclear pore complex component, RanBP2/Nup358, is required for pupal development in Drosophila. Cell Rep. 2021;37(13):110151.
- Schuller AP, Wojtynek M, Mankus D, Tatli M, Kronenberg-Tenga R, Regmi SG, Dip PV, Lytton-Jean AKR, Brignole EJ, Dasso M, Weis K, Medalia O, Schwartz TU. The cellular environment shapes the nuclear pore complex architecture. Nature. 2021;598(7882):667-671.
- Aksenova V, Smith A, Lee H, Bhat P, Esnault C, Chen S, Iben J, Kaufhold R, Yau KC, Echeverria C, Fontoura B, Arnaoutov A, Dasso M. Nucleoporin TPR is an integral component of the TREX-2 mRNA export pathway. Nat Commun. 2020;11(1):4577.
- Arnaoutov A, Lee H, Plevock Haase K, Aksenova V, Jarnik M, Oliver B, Serpe M, Dasso M. IRBIT Directs Differentiation of Intestinal Stem Cell Progeny to Maintain Tissue Homeostasis. iScience. 2020;23(3):100954.
- Arnaoutov A, Dasso M. Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase in higher eukaryotes. Science. 2014;345(6203):1512-5.
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This page was last updated on Friday, December 2, 2022