Christopher R. McMaster

Education

• PhD, University of Manitoba

Academic Positions

• Department member since 1996

Research Topics

Genetics and chemical genetics to identify drug targets and drugs for unmet medical needs

Research

Identification of drug targets and potential drugs to treat orphan diseases

One in twelve people suffer from an inherited ‘orphan disease’. While individually rare, with a single orphan disease found in less than 1 in 2000 persons, cumulatively the 7000 different known orphan diseases affect three million Canadians. As 90% of orphan diseases have no treatment, 90% are life-limiting, and 50% affect children, they carry a very large socio-economic and healthcare burden. We use cutting edge genomics technologies to discover new genes that cause orphan disease. These new gene discoveries are driving the discovery of new therapies and are offering hope to orphan disease patients by identifying and confirming therapeutic targets using genetic models of orphan disease and discovering compounds to transition to drugs to treat orphan disease patients. The end goal is to relieve the encumbrances on orphan disease patients, their families, and the health care system.

Chemiinformatics as a computational method for the design of small drug molecules

Novel antimicrobials are being developed by exploiting differences in the lipid metabolic pathways of prokaryotes versus mammalian cells. Computer aided drug design and organic synthesis of small molecules is followed by testing efficacy versus target enzymes in vitro, and on bacteria and the metabolic pathways of interest in vivo. The aim is to bring the first truly new class of antibiotics to the clinic in the past 30 years.

Genetic models to determine how cells maintain lipid homeostasis

The maintenance of lipid homeostasis is essential for normal cell growth. Alterations in lipid homeostasis can result in a myriad of diseases, most notably atherosclerosis, obesity, diabetes, and are the underlying cause of many inherited metabolic disorders. We are using genetics approaches to identifiy new genes that regulate lipid metabolism, with an eye toward genes that affect human health.

Keywords:

genetic models, drug target identification, drug discovery

Current Lab Members

Publications

1. Gaspard, GJ and McMaster, CR, (2015) The mitochondrial quality control protein Yme1 is necessary to prevent defective mitophagy in a yeast model of Barth Syndrome. J.Biol.Chem 2015 Feb 16. pii: jbc.M115.641878. [Epub ahead of print]: [PubMed] [Article]
2. Fernandez-Murray, J.P., Ngo, M.H., and McMaster, C.R., (2013) Choline Transport Activity Regulates Phosphatidylcholine Synthesis Through Choline Transporter Hnm1 Stability. J. Biol. Chem 288:36106-36115 [PubMed]
3. Beaulieu, C.L. Samuels, M.E., Ekins, S., McMaster, C.R., Edwards, A.M., Krainer, A.R., Hicks, G.G., Frey, B.J., Boycott, K.M., and MacKenzie, A.E, (2012) Generalizable Pre-clinical Research Approach for Orphan Disease Therapy Orphanet Journal of Rare Diseases 6:39
4. Beh, C.T., McMaster, C.R., Kozmonski, K.G., and Menon, A.K. , (2012) A Detour for Oxysterol-Binding Proteins J. Biol. Chem. 287:11481-11488
5. LeBlanc, M.A., and McMaster, C.R. , (2010) Lipid Binding Requirements for Oxysterol Binding Protein Kes1 Inhibition of Autophagy and Endosome-trans-Golgi Trafficking Pathways J. Biol. Chem. 285:33875-33884
6. Guernsey, D.L., Matsuoka, M., Jiang, H., Evans, S., Macgillivray, C., Nightingale, M., Perry, S., Ferguson, M., LeBlanc, M.A., Paquette, J., Patry, L., Rideout, A.L., Thomas, A., Orr, A., McMaster, C.R., Michaud, J.L., Deal, C., Langlois, S., Superneau, D, (2010) Mutations in Origin Recognition Complex Gene ORC4L Cause Meier-Gorlin Syndrome Nature Genetics 43:360-366
7. Curwin, A.J., Fairn, G.D., and McMaster, C.R, (2009) The Phospholipid Transfer Protein Sec14 is Required for Trafficking from Endosomes and Regulates Distinct trans-Golgi Export Pathways J. Biol. Chem. 284:7364-7375
8. MacKinnon, M.A., Curwin, A.J., Gaspard, G.J., Suraci, A.B., Fernández-Murray, J.P., McMaster, C.R. , (2009) The Kap60/Kap95 Karyopherin Complex Directly Regulates Phosphatidylcholine Synthesis J. Biol. Chem. 284:7376-7384
9. Fernández-Murray, J.P., Gaspard, G.J., Jesch, S.A., and McMaster, C.R. , (2009) Phosphatidylcholine Phospholipase B Neuropathy Target Esterase 1 (Nte1) Regulates Transcription of Phospholipid Biosynthetic Genes J. Biol. Chem. In press:
10. LeBlanc, M.A., and McMaster, C.R. , (2009) Surprising Roles for Phospholipid Binding Proteins Revealed by High Throughput Genetics Biochem. Cell Biol. In press:
11. Fernández-Murray, JP, Gaspard, GJ, Jesch, SA, McMaster ,CR., (2009) NTE1-encoded phosphatidylcholine phospholipase b regulates transcription of phospholipid biosynthetic genes. J.Biol.Chem 284(52):36034-46 [PubMed] [Article]
12. Fairn, G.D., and McMaster, C.R. , (2008) Emerging Roles of the Oxysterol Binding Protein Family in Metabolism, Transport, and Signaling Cell Mol. Life Sci 65:228-236
13. Curwin, A.J., and McMaster, C.R., (2008) Structure and Function of the Enigmatic Sec14 Domain Containing Proteins and the Etiology of Human Disease Future Lipidol. 3:399-410
14. Gong, H., Murphy, P.W., Langille, G.M., Minielly, S., Murphy, A., McMaster, C.R., and Byers, D. M., (2008) Tryptophan fluorescence reveals induced folding of Vibrio harveyi acyl carrier protein upon interaction with partner enzymes. BBA Proteins and Proteomics 1784:1835-1843 [PubMed]
15. Fernández-Murray, J.P., and McMaster, C.R., (2007) Phosphatidylcholine Synthesis and its Catabolism by Yeast Neuropathy Target Esterase 1 (Review) Biochim. Biophys. Acta 1771:331-336
16. Fairn, G.D., MacDonald, K., and McMaster, C. R., (2007) A Chemogenomic Screen in Saccharomyces cerevisiae Uncovers a Primary Role for the Mitochondria in Farnesol Toxicity and its Regulation by the Pkc1 Pathway J. Biol. Chem. 282:4868-4874
17. Gong, H., Murphy, A., McMaster, C.R. and Byers, D.M. , (2007) Neutralization of acidic residues in helix II stabilizes the folded conformation of acyl carrier protein and variably alters its function with different enzymes. J. Biol. Chem. 282:4494-4503 [PubMed]
18. Howe, A.L., Fairn, G.D., MacDonald, K., Bankaitis, V.A., and McMaster, C. R., (2007) Regulation of Phosphoinositide Levels by the Phospholipid Transfer Protein Sec14p Controls Cdc42p/PAK Mediated Cell Cycle Progression at Cytokinesis Euk. Cell 6:1814-1823
19. Fairn, G.D., Curwin, A.J., Stefan, C., and McMaster, C. R., (2007) Regulation of Golgi Phosphatidylinositol 4-phosphate Function by the Oxysterol Binding Protein Kes1p Proc. Natl. Acad. Sci. U.S.A. 104:15352-15357
20. Fairn, G.D., and McMaster, C. R., (2007) Emerging Roles of the Oxysterol Binding Protein Family in Metabolism, Transport, and Signaling (Review) Cell Mol. Life Sci. in press:
21. Fernández-Murray, J.P., and McMaster, C.R., (2006) Identification of Novel Phospholipid Binding Proteins in Saccharomyces cerevisiae Febs Lett. 580:82-86
22. Howe, A.G., and McMaster, C.R., (2006) Regulation of Phosphatidylcholine Homeostasis by Sec14 (Review) Can. J. Physiol. Pharmacol 84:29-38
23. Richard, K.C., Bertolesi, G.E., Dunfield, L.D., McMaster, C.R., and Nachtigal, M. W. , (2006) TSAd interacts with Smad2 and Smad3 Biochem. Biophys. Res. Comm. 347:266-272
24. Zaremberg, V., Gajate, G., Cacharro, L.M., 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
25. Bailey, K., Cook, H.W., and McMaster, C.R., (2005) The Phospholipid Scramblase PLSCR1 Increases UV Induced Apoptosis in Chinese Hamster Ovary Cells by Primarily Augmenting the Intrinsic Apoptotic Pathway Biochim. Biophys. Acta 1733:199-209
26. Wong, T., Fairn, G.D., Poon, P.P., McMaster, C.R., Singer, R.A., and Johnston, G.C. , (2005) Membrane Metabolism Mediated by Sec14p Family Members Influences ArfGAP Activity for Transport from the trans-Golgi Proc. Natl. Acad. Sci. U.S.A 102:12777-12802
27. Morash, S.M., Douglas, D., Cook, H.W., McMaster, C.R., and Byers, D.M., (2005) Expression of MARCKS Effector Domain Mutants Alters Phospholipase D Activity and Cytoskeletal Morphology of SK-N-MC Neuroblastoma Cells Neurochem. Res. 11:1353-1364 [PubMed]
28. Mohan, K., Cordeiro, E., Vaci, M., McMaster, C.R., and Issekutz, T.B., (2005) CXCR3 is Required for Migration to Dermal Inflammation by Normal and In Vivo Activated T Cells: Differential Requirements by CD4 and CD8 Memory Subsets Eur. J. of Immunol. 35:1702-1711
29. Fairn, G.D., and McMaster, C.R. , (2005) The Roles of the Human Lipid Binding Proteins ORP9S and ORP10S in Vesicular Transport Biochem. Cell Biol. 83:631-636
30. Fernández-Murray, J.P. and McMaster, C.R., (2005) Nte1p Mediated Deacylation of Phosphatidylcholine Functionally Interacts with Sec14p J. Biol. Chem. 280:8544-8552
31. Fairn, G.D. and McMaster, C.R., (2005) Identification and Assessment of the Role of a Nominal Phospholipid Binding Region of Oxysterol Binding Protein Related Protein ORP1S in the Regulation of Vesicular Transport Biochem. J. 387:889-896
32. Fairn, G.D. and McMaster, C.R. , (2005) Studying Phospholipid Metabolism Using Yeast Systematic and Chemical Genetics Methods 36:102-108
33. Taylor, M.M., MacDonald, K., Morris, A.J., and McMaster, C.R., (2005) Enhanced Apoptosis Through Farnesol Inhibition of Phospholipase D Signal Transduction FEBS J. 272:5056-5063
34. Fernández-Murray, J.P., and McMaster, C.R, (2005) Glycerophosphocholine Catabolism as a New Route for Choline Formation for Phosphatidylcholine Synthesis by the Kennedy Pathway J. Biol. Chem. 280:38290-38296
35. Fernández-Murray, J.P., and McMaster, C. R., (2005) Glycerophosphocholine Catabolism as a New Route for Choline Formation by the Kennedy Pathway J. Biol. Chem. 280:38290-38296
36. Hunt, A.N., Fenn, H.C., Clark, G.T., Wright, M.M., Postle, A.D., and McMaster, C.R., (2004) Lipidomic Analysis of the Molecular Specificity of a Cholinephosphotransferase In Situ. Biochem. Soc. Trans 32:1060-1062
37. 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
38. Howe, A.G., Zaremberg, V., and McMaster, C.R., (2002) Cessation of Growth to Prevent Cell Death Due to Inhibition of Phosphatidylcholine Synthesis is Impaired at 37C in Saccharomyces cerevisiae. J. Biol. Chem. 277:44100-44107
39. Wright, M.M., and McMaster, C.R., (2002) Phosphatidylcholine and Phosphatidylethanolamine Synthesis: Mixed Micellar Analysis of the Cholinephosphotransferase and Ethanolaminephosphotransferase Activities of Human CEPT1. Lipids 37:663-672
40. Wright, M.M., and McMaster, C.R., (2002) Phospholipid Synthesis, Diacylglycerol Compartmentation, and Apoptosis. (Review) Biol. Res. 35, 223-229 Biol. Res. 35:223-229
41. Henneberry, A.L., Wright, M.M., and McMaster, C.R., (2002) The Major Sites of Cellular Phospholipid Synthesis and Molecular Determinants of Fatty Acid and Lipid Head Group Specificity. Mol. Biol. Cell 13:3148-3161
42. Henneberry, A.L., Lagace, T.A., Ridgway, N.D., and McMaster, C.R., (2001) Phosphatidylcholine Synthesis Influences the Diacylglycerol Homeostasis Required for Sec14p Dependent Golgi Function and Cell Growth. Mol. Biol. Cell 12:511-520