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Search Results to Dannel McCollum PhD

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Role of mechanosensors and Hippo pathway signaling in controlling cell fate decisions

The main interest of my lab is in understanding how the Hippo signaling pathway controls cellular responses to mechanical forces. The Hippo pathway is a protein kinase-mediated network that regulates cell proliferation, contact inhibition, apoptosis, stem cell maintenance and differentiation, and tissue regeneration. Misregulation of this pathway has deleterious effects on cells and organisms and can lead to cancer.  In the canonical pathway, MST1/2 kinases activate the LATS1/2 kinases, which in turn phosphorylate and inhibit the transcriptional co-activator YAP by causing its translocation from the nucleus to the cytoplasm. In the nucleus, YAP promotes cell survival and proliferation. YAP nuclear localization is regulated by diverse stimuli that affect the mechanical environment of the cell such as cell crowding, substrate stiffness, tension, and cell detachment. The ability to sense these types of changes to the mechanical environment is crucial for regulation of stem cell niches, wound healing, and contact inhibition of growth.

The Hippo pathway is known to monitor the mechanical environment both indirectly through the effects of various stimuli on the actin cytoskeleton, and more directly by sensing tension across tissues. My lab’s focus has been on determining how F-actin levels and tension at cell-cell junctions are sensed, and how these signals are transduced to control Hippo signaling. We identified the angiomotin proteins as candidate Hippo pathway sensors for F-actin levels. Our studies have also uncovered new Hippo pathway regulators at cell-cell junctions that may directly sense tension across tissues. Current research in the lab is focusing on understanding the molecular mechanisms underlying F-actin and tension sensing, and how signals from separate sensors are integrated to generate cellular responses to mechanical stimuli.


One or more keywords matched the following items that are connected to McCollum, Dannel

Item TypeName
Academic Article Sid2p, a spindle pole body kinase that regulates the onset of cytokinesis.
Academic Article The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast.
Academic Article Mob1p interacts with the Sid2p kinase and is required for cytokinesis in fission yeast.
Academic Article Initiation of cytokinesis is controlled through multiple modes of regulation of the Sid2p-Mob1p kinase complex.
Academic Article Interaction between the noncatalytic region of Sid1p kinase and Cdc14p is required for full catalytic activity and localization of Sid1p.
Academic Article The meiosis-specific Sid2p-related protein Slk1p regulates forespore membrane assembly in fission yeast.
Academic Article The SIN kinase Sid2 regulates cytoplasmic retention of the S. pombe Cdc14-like phosphatase Clp1.
Academic Article The kinesin-14 Klp2 is negatively regulated by the SIN for proper spindle elongation and telophase nuclear positioning.
Academic Article Mob2p interacts with the protein kinase Orb6p to promote coordination of cell polarity with cell cycle progression.
Academic Article Phosphorylation state defines discrete roles for monopolin in chromosome attachment and spindle elongation.
Academic Article A role for metaphase spindle elongation forces in correction of merotelic kinetochore attachments.
Academic Article Identification of SIN pathway targets reveals mechanisms of crosstalk between NDR kinase pathways.
Concept Mitogen-Activated Protein Kinase Kinases
Concept CDC2 Protein Kinase
Concept Protein Kinases
Academic Article Cross talk between NDR kinase pathways coordinates cytokinesis with cell separation in Schizosaccharomyces pombe.
Academic Article The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila.

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  • Protein Kinases