Research Interests

Lipids are dynamic components of the signal transduction system required to regulate cell survival and cell death. There are important gaps in our basic understanding of lipid-mediated processes and their coordinated regulation with lipid metabolism. Lack of such coordination would result in failure of lipid homeostasis leading to disorders such as diabetes and cancer, as well as neurodegenerative and infectious diseases. Using yeast Saccharomyces cerevisiae as a model system we aim to study specific genes, proteins, and lipids whose human counterparts are poorly or incompletely characterized.

My lab is particularly interested in the study of
i) the first and rate limiting step in the synthesis of all glycerolipids catalyzed by glycerol 3-phosphate acyltransferase (GPAT). Studies include structure/function aspects of yeast GPATs, identification of protein interactions and mechanisms of regulation of their activities,
ii) the mode of action of the lipid analogue, edelfosine, a prototypical member of the alkylphosphocholine class of cancer chemotherapeutic drugs. Although edelfosine and its analogues show promise for the treatment of cancers it has been difficult to further optimize their efficacy as the cellular target of this class of drugs has yet to be identified. Based on the results of unbiased yeast genetic screens, new hypotheses are being tested involving studies on lipid microdomains, sterol traffic and phosphatidic acid signaling in yeast.

Graduate Students

Awards

2007 - University Faculty Award-NSERC(2006-2011)

Selected publications

• Marr N, Foglia J, Terebiznik M, Athenstaedt K, Zaremberg V. (2012) Controlling lipid fluxes at the glycerol 3-phosphate acyltransferase step in yeast: Unique contribution of Gat1p to oleic acid-induced lipid particle formation. J Biol Chem. 2012 Jan 21. [Epub ahead of print]
• Bitew T, Sveen CE, Heyne B, Zaremberg V. 2010 Vitamin E prevents lipid raft modifications induced by an anti-cancer lysophospholipid and abolishes a Yap1-mediated stress response in yeast. J Biol Chem. 285(33):25731-42. Epub 2010 Jun 10.
• Bratschi MW, Burrowes DP, Kulaga A, Cheung JF, Alvarez AL, Kearley J, Zaremberg V. 2009 Glycerol-3-phosphate acyltransferases gat1p and gat2p are microsomal phosphoproteins with differential contributions to polarized cell growth. Eukaryot Cell. (8):1184-96. Epub 2009 Jun 12.
• Zaremberg V, Gajate C, Cacharro LM, Mollinedo F and McMaster C R(2005) “ Cytotoxicity of the Anti-cancer Lipid Edelfosine is Through Selective Modification of Lipid Raft Composition” J Biol Chem. 280, 38047-38058
• Wright MM, Howe AG, Zaremberg V. (2004) “ Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues.” Biochem Cell Biol. 82(1):18-26.
• Zaremberg V and McMaster C R (2002) “ Differential partitioning of lipids metabolized by separate yeast glycerol-3-phosphate acyltransferases reveals that phospholipase D generation of phosphatidic acid mediates sensitivity to choline-containing lysolipids and drugs”. J Biol Chem. 277, 39035-39044
• Howe AG, Zaremberg V, McMaster CR. (2002) “ Cessation of growth to prevent cell death due to inhibition of phosphatidylcholine synthesis is impaired at 37¼C in Saccharomyces cerevisiae”. J Biol Chem. 277, 44100-44107.
• Portela P, Zaremberg V, Moreno S. (Portela and Zaremberg, equal contribution) (2001) “ Evaluation of in vivo activation of protein kinase A under non-dissociable conditions through the overexpression of wild-type and mutant regulatory subunits in Saccharomyces cerevisiae”. Microbiology 147, 1149-59.
• Zaremberg V, Donella-Deana A, Moreno S. (2000) “ Mechanism of activation of cAMP-dependent protein kinase: in Mucor rouxii the apparent specific activity of the cAMP-activated holoenzyme is different than that of its free catalytic subunit”. Arch Biochem Biophys 381, 74-82
• Zaremberg V and Moreno S. (1996) “ Analysis of the mechanism of activation of cAMP-dependent protein kinase through the study of mutants of the yeast regulatory subunit”. Eur. J. Biochem 237, 136-142