Research interests

Our laboratory utilizes the genetically tractable fission yeast, Schizosaccharomyces pombe, as a model organism to investigate signal transduction pathways that regulate cell growth and morphogenesis. The evolutionarily conserved pathways and signaling factors we study are often dysregulated in cancers and other human diseases, making our work of substantial medical relevance. There are currently two primary areas of research in our laboratory.

Schizosaccaromyces pombe

The first involves studies aimed at dissecting the complex molecular circuitry of cellular signaling and growth regulatory pathways mediated by Ras- and Rho-type p21 oncoproteins. We are particularly interested in elucidating the molecular functions of p21-activated kinases (PAKs), which comprise a highly conserved family of serine/threonine kinases that are binding targets for the Rho family proteins, Cdc42 and Rac. We and others have shown that PAKs contribute to the regulation of multiple cellular processes in eukaryotic organisms, including actin and microtubule cytoskeletal organization, polarized cell growth, cell cycle progression, and cytokinesis. Current studies in the lab are aimed at elucidating the underlying mechanisms by which PAKs regulate actin and microtubule cytoskeletal organization and cytokinesis in S. pombe. We have identified a number of PAK substrate targets in S. pombe and are in process of elucidating the mechanisms by which these proteins modulate PAK cytoskeletal and cytokinetic regulatory functions.

The second major area of study in our lab involves investigations aimed at characterizing novel signaling pathways involved in mediating cellular responses to osmotic and other extracellular stresses. We recently identified a novel phospholipase B (PLB)-mediated osmotic stress response pathway in S. pombe and are carrying out studies to identify and characterize its molecular components. Genetic screens have identified several candidate downstream effectors of PLB activity in S. pombe, including components of the cAMP/protein kinase A pathway, the 26S proteasome, and several novel evolutionarily conserved proteins. This project has also revealed novel roles for the phospholipid phosphatidylserine in osmotic stress response and the regulation of cellular morphogenesis.

Selected publications

Gutterman JU, Lai HT, Yang P, Haridas V, Gaikwad A, and 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, and 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, and 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, and 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, and 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, and 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, and 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.

Bao S, Qyang Y, Yang P, Kim H, Du H, Bartholomeusz G, Henkel J, Pimental R, Verde F, and Marcus S (2001) The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast, Schizosaccharomyces pombe. J Biol Chem 276:14549-52.

Henkel J, Du H, Yang P, Qyang Y, Kansra S, Ko M, Kim H, and Marcus S (2001) Bob1, a Gim5/MM-1/Pfd5 homolog, interacts with the MAP kinase kinase Byr1 to regulate sexual differentiation in the fission yeast, Schizosaccharomyces pombe. Differentiation 67:98–106.

Kim HW, Yang P, Qyang Y, Lai H, Du H, Henkel J, Kumar K, Bao S, Liu M, and 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, and 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.