Office: MRB 241
Phone: (970) 491-5979
- Ph.D., New York University Medical Center
Our laboratory is focused on understanding the mechanisms regulating motor-based transport in cells, with a particular focus during mitosis. A fundamental and critical aspect of eukaryotic cells is their complex and well-defined internal organization. This high level of internal organization is achieved in large part by the well orchestrated motor-mediated delivery of various cargo to appropriate sites within the cell. The microtubule motors dynein and kinesin mediate the directional transport of cellular cargo (including the mitotic spindle) in the minus and plus end direction, respectively (i.e., toward the cell center, and the cell periphery, respectively). How these motors are regulated to carry out their respective functions is a central question in cell biology. We have recently identified a microtubule associated protein, She1, as a molecule with the ability to differentially affect the motility of dynein and kinesin. How this molecule achieves its motor specificity, and how this molecule is regulated within cells is unclear, and is one of the focuses of our laboratory. Techniques utilized by our lab include fluorescent microscopy (traditional wide-field, confocal, and total internal reflection fluorescence (TIRF) microscopy), genetics, biochemistry and various molecular biological approaches. For instance, using TIRF microscopy, we can watch single molecules of molecular motors walking along their respective tracks (see movies below). We expect that our findings will have implications for basic cellular biology, and also for understanding the pathogenesis of various disease states. For instance, aneuploidy (improper chromosome number) and tumor initiation correlate with defects in dynein mediated spindle positioning during cell division.
Cool Movies: Click on the following links to watch movies acquired using time-lapse fluorescence microscopy. Each movie shows examples of purified molecular motors walking along microtubule tracks.
- Zn2+ decoration of microtubules arrests axonal transport and displaces tau, doublecortin, and MAP2C J Cell Biol, 2023.
- Microtubule binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport Nat Struc Mol Biol, 2023.
- Conserved roles of the dynein intermediate chain and Ndel1 in assembly and activation of dynein Nat Comm.
- CMPD1 is a microtubule poison with tumor-specific cytotoxicity n/a.
- Methods in Molecular Biology: DyneinMethods in Molecular Biology: Dynein Methods in Molecular Biology, 2023.
- Using budding yeast as a model to understand dynein-mediated cargo transportMethods in Molecular Biology: Dynein Methods in Molecular Biology, 2023.
- The role of Dynein in silencing the spindle assembly checkpoint is limited to disassembly of the fibrous corona Mol Biol Cell.
- The microtubule-associated protein She1 coordinates directional spindle positioning by spatially restricting dynein activity Journal of Cell Science, 23.
- Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein function Molecular Biology of the Cell, 20, 2021.
- New insights into the mechanism of dynein motor regulation by lissencephaly-1 Elife.
- Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity Nature Cell Biology, 5, 2020.
- Molecular Basis for Dyneinopathies Reveals Insight Into Dynein Regulation and Dysfunction Elife, 2019.
- Effectors of the Spindle Assembly Checkpoint Are Confined Within the Nucleus of Saccharomyces Cerevisiae Biology Open, 6, 2019.
- She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain Nature Communications, 1, 2017.
- 'Wait Anaphase' Signals Are Not Confined to the Mitotic Spindle Molecular Biology of the Cell, 2017.
- Improved Plasmids for Fluorescent Protein Tagging of Microtubules in Saccharomyces cerevisiae Traffic, 2015.
- The dynein cortical anchor Num1 activates dynein motility by relieving Pac1/LIS1-mediated inhibition The Journal of cell biology, 2, 2015.
- Astral microtubule asymmetry provides directional cues for spindle positioning in budding yeast Experimental cell research, 12, 2012.
- She1-mediated inhibition of dynein motility along astral microtubules promotes polarized spindle movements Current Biology, 23, 2012.
- Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation Bioarchitecture, 5, 2011.
- Quantitative analysis of Pac1/LIS1-mediated dynein targeting: Implications for regulation of dynein activity in budding yeast Cytoskeleton, 3, 2011.
- Regulated offloading of cytoplasmic dynein from microtubule plus ends to the cortex Developmental cell, 5, 2011.
- Motor-and tail-dependent targeting of dynein to microtubule plus ends and the cell cortex Current Biology, 3, 2009.
- Photoactivatable GFP tagging cassettes for protein-tracking studies in the budding yeast Saccharomyces cerevisiae Yeast, 9, 2008.
- Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus Molecular biology of the cell, 2, 2002.
- Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cells Proceedings of the National Academy of Sciences, 15, 2001.