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Steven Markus
Steven Markus Associate Professor

Office: MRB 241

Phone: (970) 491-5979

Website: https:\\markuslab.colostate.edu

Education

  • Ph.D., New York University Medical Center

About

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.

Human Kinesin-1 motors walking.

Yeast Kip2 motors walking.

Yeast Dynein (red) and Kip2 (green) motors walking.

Publications

  • Zn2+ decoration of microtubules arrests axonal transport and displaces tau, doublecortin, and MAP2CTaylor F. Minckley, Anna M. Dischler, Dylan Fudge, Ebrahim Ghazvini Zadeh, Wen-Hong Li, Kristen J. Verhey, Steven M. Markus, Yan Qin J Cell Biol, 2023.
  • Microtubule binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transportWilliam Ton, Pengxin Chai, Yue Wang, Cece Beauchamp-Perez, Nicholas Thomas Flint, Hao Xiong, Lindsay G. Lammers, Kai Zhang, Steven M. Markus Nat Struc Mol Biol, 2023.
  • Conserved roles of the dynein intermediate chain and Ndel1 in assembly and activation of dyneinKyoko Okada, Bharat Iyer, Lindsay G. Lammers, Pedro Gutierrez, Wenzhe Li, Steven M. Markus, Richard J. McKenney Nat Comm.
  • CMPD1 is a microtubule poison with tumor-specific cytotoxicityYu-Chia Chen, Mamoru Takada, Aerica Nagornyuk, Wang Junchiao, Wu Muhan, Hideyuki Yamada, Takeshi Nagashima, Steven M. Markus, Jennifer G. DeLuca, Masayuki Ohtsuka, Motoki Takaku, Aussie Suzuki n/a.
  • Methods in Molecular Biology: DyneinMethods in Molecular Biology: DyneinSteven M. Markus Methods in Molecular Biology, 2023.
  • Using budding yeast as a model to understand dynein-mediated cargo transportMethods in Molecular Biology: DyneinKari Hope Ecklund, Matthew George Marzo, Steven M. Markus Methods in Molecular Biology, 2023.
  • The role of Dynein in silencing the spindle assembly checkpoint is limited to disassembly of the fibrous coronaAmy Hodges, Keith F. DeLuca, O'Neil P. Wiggan, Steven M. Markus, Jennifer G. DeLuca Mol Biol Cell.
  • The microtubule-associated protein She1 coordinates directional spindle positioning by spatially restricting dynein activityKari Hope Ecklund, Megan Bailey, Carsten Jacobus Dietvorst, Kelly A. Kossen, Charles Asbury, Steven M. Markus Journal of Cell Science, 23.
  • Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein functionE. Dénarier, Kari Hope Ecklund, G. Berthier, M. Poitevin, A. Favier, S. Gory, C. Delphin, A. Andrieux, Steven M. Markus, Cécile Boscheron Molecular Biology of the Cell, 20, 2021.
  • New insights into the mechanism of dynein motor regulation by lissencephaly-1Steven M. Markus, Matthew George Marzo, Richard J. McKenney Elife.
  • Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activityMatthew George Marzo, Griswold M. Jacqueline, Steven M. Markus Nature Cell Biology, 5, 2020.
  • Molecular Basis for Dyneinopathies Reveals Insight Into Dynein Regulation and DysfunctionMatthew George Marzo, Jacqueline M. Jacqueline, Kristina M. Ruff, Rachel Emily Buchmeier, Fees Colby, Steven M. Markus Elife, 2019.
  • Effectors of the Spindle Assembly Checkpoint Are Confined Within the Nucleus of Saccharomyces CerevisiaeLydia Rene Heasley, Jennifer G. DeLuca, Steven M. Markus Biology Open, 6, 2019.
  • She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domainKari Hope Ecklund, Tatsuya Morisaki, Lindsay G. Lammers, Matthew George Marzo, Tim John Stasevich, Steven M. Markus Nature Communications, 1, 2017.
  • 'Wait Anaphase' Signals Are Not Confined to the Mitotic SpindleLydia Rene Heasley, Steven M. Markus, Jennifer G. DeLuca Molecular Biology of the Cell, 2017.
  • Improved Plasmids for Fluorescent Protein Tagging of Microtubules in Saccharomyces cerevisiaeSteven M. Markus, Safia Omer, Kaitlyn Baranowski, Wei-Lih Lee Traffic, 2015.
  • The dynein cortical anchor Num1 activates dynein motility by relieving Pac1/LIS1-mediated inhibitionLindsay G. Lammers, Steven M. Markus The Journal of cell biology, 2, 2015.
  • Astral microtubule asymmetry provides directional cues for spindle positioning in budding yeastSteven M. Markus, Katelyn A. Kalutkiewicz, Wei-Lih Lee Experimental cell research, 12, 2012.
  • She1-mediated inhibition of dynein motility along astral microtubules promotes polarized spindle movementsSteven M. Markus, Katelyn A. Kalutkiewicz, Wei-Lih Lee Current Biology, 23, 2012.
  • Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientationSteven M. Markus, Wei-Lih Lee Bioarchitecture, 5, 2011.
  • Quantitative analysis of Pac1/LIS1-mediated dynein targeting: Implications for regulation of dynein activity in budding yeastSteven M. Markus, Karen M. Plevock, Bryan J. St Germain, Jesse J. Punch, Christopher W. Meaden, Wei-Lih Lee Cytoskeleton, 3, 2011.
  • Regulated offloading of cytoplasmic dynein from microtubule plus ends to the cortexSteven M. Markus, Wei-Lih Lee Developmental cell, 5, 2011.
  • Motor-and tail-dependent targeting of dynein to microtubule plus ends and the cell cortexSteven M. Markus, Jesse J. Punch, Wei-Lih Lee Current Biology, 3, 2009.
  • Photoactivatable GFP tagging cassettes for protein-tracking studies in the budding yeast Saccharomyces cerevisiaeChristina Vorvis, Steven M. Markus, Wei-Lih Lee Yeast, 9, 2008.
  • Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminusSteven M. Markus, Samir S. Taneja, Susan K. Logan, Wenhui Li, Susan Ha, Adam B. Hittelman, Inez Rogatsky, Michael J. Garabedian Molecular biology of the cell, 2, 2002.
  • Enhanced antitumor efficacy of a herpes simplex virus mutant isolated by genetic selection in cancer cellsSamir Taneja, Jennifer MacGregor, Steven M. Markus, Susan Ha, Ian Mohr Proceedings of the National Academy of Sciences, 15, 2001.