Stevan  Marcus

Associate Professor


Education

  • Ph.D., Cellular, Molecular and Developmental Biology, University of Tennessee, 1991
  • Postdoctoral research: Cold Spring Harbor Laboratory

Research Interests

Research in our laboratory focuses on studies aimed at understanding the molecular regulation and function of signal transduction networks that control cell division, cellular morphogenesis, and adaptations to physiological stresses in eukaryotic organisms. Dysfunction in these control systems can be causative or contributory to a variety of human diseases, including cancers, cardiovascular and neurodegenerative diseases, and developmental disorders. The unicellular eukaryote, Schizosaccharomyces pombe, is the primary model organism used for our research. S. pombe, also known as fission yeast, is a rod-shaped yeast that grows by tip extension and divides by medial fission to produce two daughter cells of approximately equal sizes (see above figure). Its highly polarized morphology and cell cycle-coordinated patterns of growth and cytoskeletal remodeling make S. pombe a very attractive model organism for research on regulation of the cell cycle control system and cellular morphogenesis. Indeed, a fission yeast researcher, Paul Nurse, shared the 2001 Nobel Prize in Physiology or Medicine with two other scientists, Lee Hartwell (budding yeast researcher) and Tim Hunt (sea urchin researcher), for seminal research that identified the basic molecular machinery of the cell cycle control system shared by all eukaryotic organisms, including humans.

Photomicrographs of wild type S. pombe cells visualized by differential interference contrast microscopy (A), and by fluorescence microscopy of cells stained with rhodamine phalloidin for visualization of the actin cytoskeleton (B).

Our research is currently focused on elucidating novel mechanisms by which fission yeast regulate their cell cycle control system and other physiological functions in response to environmental stresses. In particular, we are interested in deciphering mechanisms by which a protein kinase found in all eukaryotic organisms, cyclic AMP-dependent protein kinase (PKA), interacts in highly coordinated fashion with multiple stress response factors to control a variety of adaptive responses to environmental stresses. Recent investigations related to this endeavor have revealed critical roles for PKA in cell cycle control in certain physiologically stressed conditions and in the maintenance of mitochondrial integrity in both normal and physiologically stressed states. Our experimental findings suggest that further characterization of the PKA-dependent stress response systems of S. pombe may provide novel insights into mechanisms of physiological stress adaptation that are relevant to the process of aging and the etiology of Parkinson’s disease, a debilitating neurodegenerative disorder in which mitochondrial dysfunction is linked to disease pathology. Genetic screens being conducted to further dissect the PKA-dependent mitochondrial integrity system of S. pombe may result in the identification of potential therapeutic targets for Parkinson’s disease as well as other neurodegenerative disorders in which mitochondrial dysfunction is causative or contributory to disease pathology.

The Marcus research team consists of both undergraduate and graduate students as well postdoctoral scientists. Individuals who are self-motivated, eager to gain modern biomedical research experience, and genuinely interested in making meaningful contributions to cutting edge cell and molecular biology research are welcome to meet with Dr. Marcus to explore opportunities for joining his research team.

Publications

Marchione D, Yuan Z, Nichelson J, and Marcus S. Resistance to the anti-tumor saponin avicin G is mediated a novel endocytosis and microtubule mediated sterol sequestering system in the fission yeast, Schizosaccharomyces pombe. Manuscript in preparation.

Yuan Z, Nichelson J, and Marcus S. Protein kinase A, TOR, and autophagy function synergistically in mediating resistance to the mitochondrial toxin rotenone in fission yeast. Manuscript in preparation.

Wang Y, Wang Y, Marcus S, and Busenlehner LS. Dissecting the role of frataxin in Friedreich’s ataxia using a fission yeast model system. Manuscript in preparation.

Yuan Z, Wang Y, Strange E, and Marcus S. Protein kinase A is required for resistance to the lysosomotropic drugs quinacrine and chloroquine in the fission yeast, Schizosaccharomyces pombe. Manuscript submitted.

Watson HM, Gentry LE, Asuru AP, Wang Y, Marcus S, Busenlehner LS (2012) Heterotrifunctional chemical cross-linking mass spectrometry confirms physical interaction between human frataxin and ISU. Biochemistry 51:6889-6891.

McInnis B, Mitchell J, and Marcus S (2010) Phosphorylation of the protein kinase A catalytic subunit is induced by cyclic AMP deficiency and physiological stresses in the fission yeast, Schizosaccharomyces pombe. Biochem Biophys Res Commun 399:665-669.

Wang Y, Gulis G, Buckner S, Johnson PC, Sullivan D, Busenlehner L, and Marcus S (2010) The MAP kinase Pmk1 and protein kinase A are required for rotenone resistance in the fission yeast, Schizosaccharomyces pombe. Biochem Biophys Res Commun 399:123-128.

Luo J, Matsuo Y, Gulis G, Hinz H, Patton-Vogt J, and Marcus S (2009) Phosphatidylethanolamine is required for normal cell morphology and cytokinesis in the fission yeast, Schizosaccharomyces pombe. Eukaryotic Cell 8:790–799.

Matsuo Y, McInnis B, and Marcus S (2008) Regulation of the subcellular localization of cyclic AMP-dependent protein kinase in response to physiological stresses and sexual differentiation in the fission yeast Schizosaccharomyces pombe. Eukaryotic Cell 7:1450–1459.

Matsuo Y, Fisher E, Yang P, Patton-Vogt J, and Marcus S (2007) Functional characterization of the fission yeast phosphatidylserine synthase gene, pps1, reveals novel cellular functions for phosphatidylserine. Eukaryotic Cell 6:2092–2101.

Gutterman JU, Lai HT, Yang P, Haridas V, Gaikwad A, Marcus S (2005) Effects of the tumor inhibitory triterpenoid avicin G on cell integrity, cytokinesis, and protein ubiquitination in fission yeast. Proc Natl Acad Sci USA. 102:12771–12776.

Vadlamudi RK, Barnes CJ, Rayala S, Li F, Balasenthil S, Marcus S, Goodson HV, Sahin AA, Kumar R (2005) p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B. Mol Cell Biol 25:3726-3736.

Wu CF, Yang P, Traverso EE, Etkin LD, and Marcus S (2004) The Xenopus laevis morphogenetic factor, Tumorhead, causes defects in polarized growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe. Biochem Biophys Res Comm 325:439-44.

Kim H, Yang P, Wiley DJ, Verde F, Lai H, Du H, Chang F, Marcus S (2003) The kelch repeat protein, Tea1, is a potential substrate target of the p21-activated kinase, Shk1, in the fission yeast, Schizosaccharomyces pombe. J Biol Chem 278:30074-82.

Wiley DJ, Marcus S, D’Urso G, Verde F (2003) Control of cell polarity in fission yeast by association of Orb6p kinase with the highly conserved protein methyltransferase Skb1p. J Biol Chem 278:25256–63.

Yang P, Du H, Hoffman CS, Marcus S (2003) The phospholipase B homolog, Plb1, is a mediator of osmotic stress response and nutrient-dependent repression of sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Mol Genet Genomics 269:116-25.

Yang P, Qyang Y, Bartholomeusz G, Zhou X, Marcus S (2003) The novel Rho GTPase-activating protein family protein, Rga8, provides a potential link between Cdc42/p21-activated kinase and Rho signaling pathways in the fission yeast, Schizosaccharomyces pombe. J Biol Chem 278: 48821-30.

Qyang Y, Yang P, Du H, Lai H, Kim H, Marcus S (2002) The p21-activated kinase, Shk1, is required for proper regulation of microtubule dynamics in the fission yeast, Schizosaccharomyces pombe. Mol Microbiol 44:25-334.

Kim HW, Yang P, Qyang Y, Lai H, Du H, Henkel J, Kumar K, Bao S, Liu M, Marcus S (2001) Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1. Molecular Cell 7:1095-1101.

Xia C, Ma W, Stafford LJ, Marcus S, Xiong WC, Liu M (2001) Regulation of the p21-activated kinase (PAK) by a novel human G?-like WD-repeat protein, hPIP1. Proc Natl Acad Sci USA 98:6174-9.