Loewen

Christopher J. R. Loewen, Associate Professor

Tula Foundation Investigator (Brain Research Centre)
CIHR New Investigator
MSFHR Scholar

Member, Cell and Developmental Biology Research Group (Life Sciences Institute)

Postdoc: University College London, UK (2005)
PhD: University of British Columbia (2001)
BSc (Hon): University of British Columbia (1995)

Office:  604-827-5961, Lab: 604-827-4160
E-mail:  christopher.loewen@ubc.ca

 

R e s e a r c h   I n t e r e s t s

Membrane Contact Sites and Lipid Traffic

Lipids play important roles in all cells. They differ from many other hydrophilic biological molecules in that they are hydrophobic and do not mix in the aqueous environment of cells. In this way they can function to separate the cell from the outside environment and also divide the cell into distinct compartments, called organelles. Compartmentalisation by organelles is critical for carrying out different cellular processes. For example, the integrity of mitochondria is essential to the cell to produce energy (ATP) and to regulate cell death (apoptosis).

It is also imperative that these organelles communicate with each other. Communication of the endoplasmic reticulum (ER) with other organelles, for example mitochondria, is especially important to the cell because the ER is the site of many metabolic activities including making lipids and proteins. The focus of my research is to better understand how the ER contacts, and hence communicates with other organelles through defining the molecules that mediate these contacts. Studying these membrane contact sites is important for human health and disease because their disruption can result in defective movement of lipids, cell stress and cell death. Accumulation of lipids is a factor in many diseases including atherosclerosis, Alzheimer’s disease, type 2 diabetes and motorneuron disease, but in many cases what causes this accumulation is not known. Studies in my laboratory on defining membrane contact sites and lipid traffic will help to uncover mechanisms of disease and potentially lead to novel drug targets and therapies for these disorders, thus contributing to the general health of Canadians.

Currently, my lab uses the model organism Saccharomyces cerevisiae to study this problem. We employ standard techniques in yeast genetics, biochemistry and molecular cell biology with the aim to identify the components of membrane contact sites and their roles in lipid traffic. Soon we will be incorporating sophisticated genomic and proteomic methodologies to identify new sets of genes/proteins to gain a better understanding of this process on a global scale. At present, we are investigating the role of a highly conserved protein called VAP in formation of a membrane contact site between the ER and plasma membrane. Because ER membrane contact sites are present in all eukaryotes, the genes we identify in yeast will likely be conserved in humans and will therefore be directly relevant to human cell biology. VAP has also recently been found to cause a form of motorneuron disease called Amyotrophic lateral sclerosis, and we are hopeful that our work in yeast will be relevant to this disease.

Further Reading

Levine, T. (2004) Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions. Trends Cell Biol. 14, 483-90.

A Broken Barrier Theory of ALS

•  I am currently recruiting graduate students to join the lab.

Please email me with your CV attached if you are interested.  •

S e l e c t e d   P u b l i c a t i o n s
  1. Ho KL, Ma L, Cheung S, Manhas S, Fang N, Wang K, Young B, Loewen C, Mayor T, Measday, V. (2015) A role for the budding yeast separase, Esp1, in Ty1 element retrotransposition. PLoS Genet 11:e1005109. [IF 8.17].
  2. Lahiri S*, Chao JT*, Tavassoli S, Wong AKO, Choudhary V, Young BP, Loewen CJR, Prinz WA (2014) A Conserved Endoplasmic Reticulum Membrane Protein Complex (EMC) Facilitates Phospholipid Transfer from the ER to Mitochondria. PLoS Biol. 12: e1001969. [IF 3].
  3. Chao JT, Wong AKO, Tavassoli S, Young BP, Chruscicki A, Fang NN, Howe LJ, Mayor T, Foster LJ, Loewen CJR*. (2014) Polarization of the Endoplasmic Reticulum by ER-Septin Tethering. Cell 158: 620–632. [IF 2].
  4. Wong AK*, Chao JT*, Loewen CJ*. (2014) Barriers to uniformity within the endoplasmic reticulum. Opin. Cell Biol 29C: 31–38.
  5. Riekhof WR, Wu WI, Jones JL, Nikrad M, Chan MM, Loewen CJR, Voelker DR. (2013) An assembly of proteins and lipid domains regulates transport of phosphatidylserine to phosphatidylserine decarboxylase 2 in Saccharomyces cerevisiae. J Biol. Chem. [IF 6].
  6. Tavassoli S, Chao JT, Young BP, Cox RC, Prinz WA, de Kroon AI, Loewen CJR*. (2013) Plasma membrane–endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis. EMBO Rep 14: 434–440. [IF 8.9].
  7. Young BP, Loewen CJR*. (2013) Balony: a software package for analysis of data generated by synthetic genetic array experiments. BMC Bioinformatics 14: 354. [IF 2.576].
  8. Raychaudhuri S, Young BP, Espenshade PJ, Loewen CJ* (2012) Regulation of lipid metabolism: a tale of two yeasts. Current Opinion in Cell Biology 24(4): 502-508. [IF 4].
  9. McQueen J, van Dyk D, Young B, Loewen C, Measday V. (2012) The Mck1 GSK-3 kinase inhibits the activity of Clb2-Cdk1 post-nuclear division. Cell Cycle 11(18): 3421–3432. [IF 0].
  10. Voss C, Lahiri S, Young BP, Loewen CJ, Prinz WA (2012) ER-shaping proteins facilitate lipid exchange between the ER and mitochondria in S. cerevisiae. Journal of Cell Science, 125(Pt 20): 4791–4799. [IF 2].
  11. Loewen CJR*. (2012) Lipids as conductors in the orchestra of life. F1000 Biology Reports 4: 4 -10.
  12. Shin JJ, Loewen CJ*. (2011) Putting the pH into phosphatidic acid signaling. BMC Biology 9: 85-96. [IF 0].
  13. Bleackley MR, Young BP, Loewen CJ, Macgillivray RT. (2011) High density array screening to identify the genetic requirements for transition metal tolerance in Saccharomyces cerevisiae. Metallomics 3(2): 195–205. [IF 9].
  14. Young BP, Shin JJ, Orij R, Chao JT, Li SC, Guan XL, Khong A, Jan E, Wenk MR, Prinz WA, Smits GJ, Loewen CJ*. (2010) Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism. Science 329(5995): 1085–1088. [IF 9].
  15. Chruscicki A, Macdonald VE, Young BP, Loewen CJ, Howe LJ. (2010) Critical determinants for chromatin binding by Saccharomyces cerevisiae Yng1 exist outside of the plant homeodomain finger. Genetics 185(2): 469–477. [IF 8].
Further publications can be found here.
I m a g e s

Arraying yeast to 1536 density at WARP-speed with our Singer Rotor robot