Dr. Amanda MacFarlane

Image Amanda MacFarlane
Research Scientist and Head of the Micronutrient Research Section

I am the Head of the Water Soluble B Vitamins Lab at Health Canada with a research focus on folate and B vitamin-mediated one-carbon metabolism and their relationship to parental, offspring and population health.

Current research and/or projects

My lab studies folate-mediated one-carbon (1C) metabolism in health and disease. Folic acid (folate), along with the other essential B vitamins, is required for DNA synthesis and cellular methylation reactions. Folate-mediated 1C metabolism provides 1C groups for the de novo synthesis of purines, thymidylate, and methionine. Nucleotide pool imbalances (too much or too little of one nucleotide) can result in cytotoxicity, DNA mutagenesis, genome instability and changes in gene expression. Methionine is used to form S-adenosylmethionine (AdoMet) the major methyl donor in the cell required for DNA, RNA and histone methylation, which impacts genome stability and the expression of epigenetically regulated genes. Using in vitro and in vivo models, my lab examines the biochemical, genetic and epigenetic mechanisms underpinning folate-dependent diseases with a particular interest in the effect of maternal and paternal nutrition on fertility, and its effect on the health of their offspring. Using nationally-representative population health data, we also assess the folate and B vitamin status of Canadians, and identify socioeconomic, dietary and genetic determinants of status in the Canadian population. I am also actively involved in policy work related to food fortification and supplement use, and international standard setting including the Dietary Reference Intakes.

Professional activities / interests

2018-present  Associate Editor. The American Journal of Clinical Nutrition

2018-present  Co-Chair. US-Canada Special Nutrient Requirements in Disease States Federal Working Group

2018              Reviewer. National Academies of Sciences, Engineering, and Medicine. 2018. Harmonization of Approaches to Nutrient Reference Values: Applications to Young Children and Women of Reproductive Age. Washington, DC: The National Academies Press.

2017, 2018     Peer reviewer. Canadian Institutes of Health Research Nutrition, Food and Health Committee - Project Grant Competition

2016-2017      Workshop co-organizer, “Periconceptional intake of folic acid among low-risk women: aligning prenatal supplement content with current expert guidelines”. Ottawa, ON (Nov 2017)

2015              Reviewer. Canadian Institutes of Health Research Science Policy Fellowship Program

2014-2017      Project co-director, “Options for Addressing Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs)”. This includes the development and organization of a Workshop in March 2015 sponsored by the Canadian and US Federal DRI Steering Committees and drafting and publication of the subsequent report.

2014-2015      Member, Steering Committee for Evaluating the Safe Use of High Intakes of Folic Acid sponsored by Office of Health Assessment and Translation, US National Toxicology Program and NIH Office of Dietary Supplements

2013-present  Chair, Joint Canada-US Dietary Reference Intakes Working Group

2013-present  Member, Canadian Interdepartmental/Interagency Steering Committee on the Dietary Reference Intakes

2013-2015      Advisor, Regulatory Revisions to the Canadian Nutrient Facts Table, Health Canada

2011-present  Member, Interagency Folic Acid Working Group, Public Health Agency of Canada and Health Canada

2010-2012      Special contributor. Review of the Society of Obstetricians and Gynaecologists of Canada recommendation for Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital     Anomalies, guideline published in 2015

2011-present  Guest speaker (Grades 5-12), Virtual Researcher on Call Program by Partners in Research

2010-2013      Member, Faculty of Graduate and Postdoctoral Studies, University of Ottawa

2010-present  Review editorial board. Frontiers in Nutrigenomics

2010              International observer. NHANES Monitoring of Biomarkers of Folate and Vitamin B12 Status: Measurement Procedure Issues

2010-2017      Lecturer/evaluator. BCH3120 General intermediary metabolism/BCH4932 Biochemistry Seminars/BCH8106 Advanced Topics in Nutrition and Regulation of Metabolism. University of Ottawa, Ontario

2009-2010      Health Canada Lead. Federal Food Safety and Nutrition Research Meeting Organizing Committee, Health Canada, Ottawa, Ontario

Education and awards

Education

2004 – 2007   Post-Doctoral Research Associate, Division of Nutritional Sciences, Cornell University, Ithaca, NY

2004               Post-Doctoral Research Associate, Ottawa Health Research Institute, Ottawa, ON

2000 – 2004   Ph.D. in Biochemistry, University of Ottawa, Ottawa, Ontario

1996 – 2000   B.Sc. Highest Honours in Biology and Biotechnology, Carleton University, Ottawa, Ontario

Awards

2017              Deputy Minister’s Award for Excellence in Science – New DRI Framework Team (with Linda Greene-Finestone)

2015              Assistant Deputy Minister’s Award for Transparency and Openness for The Dietary Reference Intakes Nomination Process Team (Team lead)

2010              Outstanding Poster Prize, Federal Food Safety and Nutrition Research Meeting

2006              FASEB Summer Research Conference: Folic Acid, Vitamin B12 & One Carbon Metabolism, Travel           Award ($600)

2001-2004     Ontario Ministry of Training, Colleges and Universities, Ontario Graduate Scholarship ($15,000 per year)

2001-2004     University of Ottawa Excellence Scholarship ($5,235 per annum)

2001 & 2004  University of Ottawa, Department of Biochemistry Travel Grant ($1,000 per award)

2002 & 2004  University of Ottawa, Faculty of Graduate and Postdoctoral Studies Travel Grant ($400 per award)

2003              Juvenile Diabetes Research Foundation Ron Oelbaum Diabetes Research Award for an Outstanding Canadian Research Scientist under 35 ($2,000)

2002 & 2003  University of Ottawa Strategic Areas of Development Award ($6,000 per annum)

2002              University of Ottawa Admission Scholarship - Ph.D. Graduate Studies ($10,860)

2000              Carleton University NSERC Undergraduate Student Research Award (declined) ($4,500)

2000              Carleton University Dean’s list

2000              Canadian Millennium Scholarship Foundation Scholarship ($3,000)

1996              Carleton University Academic Award ($500)

Key publications

Journal articles in press or published (underline indicates trainee or staff)

  1. Liu, S., J. Evans, A.J. MacFarlane, C.V. Ananth, J. Little, M.S. Kramer, K.S. Joseph for the Canadian Perinatal Surveillance System. Association of Maternal Risk Factors with the Recent Rise of Neural Tube Defects in Canada. Accepted in Paediatric and Perinatal Epidemiology.

  2. MacFarlane, A.J., M.E. Cogswell, J. de Jesus, L. Greene-Finestone, D.M. Klurfeld, C.J. Lynch, K. Regan, S. Yamini. A report of activities related to the Dietary Reference Intakes from the Joint Canada-US Dietary Reference Intakes Working Group. Am J Clin Nutr 109: 1-9. 2019.

  3. Lowry, R.B., T. Bedard, A.J. MacFarlane, S. Crawford, B. Sibbald, B.C. Agborsangaya. Prevalence rates of Spina Bifida in Alberta, Canada: 2001-2015. Why can’t we do better with prevention? Birth Defects Research 111(3): 151-158. 2019.

  4. Lamers, Y., A.J. MacFarlane, D.L. O’Connor, B. Fontaine-Bisson. Periconceptional intake of folic acid among low-risk women: summary of a workshop aiming to align prenatal folic acid supplement composition with current expert guidelines. Am J Clin Nutr 108(6):1357-1368. 2018.

  5. Jadavji, N.M., J.T. Emmerson, U. Shanmugalingam, A.J. MacFarlane, W.G. Willmore, P.D. Smith. A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke. Exp Neurol 309:14-22. 2018.

  6. LeBlanc, D., N. Behan, J.M. O’Brien, F. Marchetti, A.J. MacFarlane. Folate deficiency increases chromosomal damage and mutations in hematopoietic cells in the transgenic MutaMouse model. Environ Mol Mutagen. 59(5):366-374. 2018.

  7. Ly, L., D. Chan, M. Aarabi, M. Landry, N. Behan, A.J. MacFarlane, J. Trasler. Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation. Mol Hum Reprod 23(7):461-477. 2017.

  8. Page, R., A. Robichaud, T. Arbuckle, W. Fraser and A.J. MacFarlane. Total folate and unmetabolized folic acid in the breast milk of a cross-section of Canadian women. Am J Clin Nutr 105(5):1101-1109. 2017.

  9. Jadavji, N.M., J.T. Emmerson, A.J. MacFarlane, W.G. Willmore, P.D. Smith. B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke. Neurobiol Dis 103:89-100. 2017.

  10. Yetley E.A., A.J. MacFarlane, L.S. Green-Finestone, B.G. Garza, et al. Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: Report from a Joint US/Canadian-sponsored working group.Am J Clin Nutr 105(1): 249S-285S. 2017.

  11. Lévesque N., K.E. Christensen, L. Van Der Kraak, A.F. Best, L. Deng, D. Caldwell, A.J. MacFarlane, N. Beauchemin, R. Rozen. Murine MTHFD1-synthetase deficiency, a model for the human MTHFD1 R653Q polymorphism, decreases growth of colorectal tumors. Mol Carcinog 56(3):1030-1040. 2017.

  12. MacFarlane, A.J. The elephant in the room: Using nutritional biomarker cut-offs to assess status. Am J Clin Nutr 104(6): 1493-1494. 2016.

  13. Shen M., S.H. Chaudhry, A.J. MacFarlane, L. Gaudet, G.N. Smith, M. Rodger, R.R. White, M.C. Walker, S.W. Wen. Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women. Public Health Nutr 18:1-8. 2016.

  14. Ahmed, T., I. Fellus, J. Gaudet, A.J. MacFarlane, B. Fontaine-Bisson, S. Bainbridge. Effect of folic acid on human trophoblast health and function in vitro. Placenta 37: 7-15. 2016.

  15. Xie, R.H., Y.J. Liu, R. Retnakaran, A.J. MacFarlane, J. Hamilton, G. Smith, M.C. Walker, S.W. Wen. Maternal folate status and obesity/insulin resistance in the offspring: A systematic review. Int J Obes (Lond) 40(1): 1-9. 2016.

  16. Chan Y.-M., A.J. MacFarlane, D.L. O’Connor. Modeling demonstrates that folic acid fortification of whole wheat flour could reduce the prevalence of folate inadequacy in Canadian whole-wheat consumers. J Nutr 145(11):2622-9. 2015.

  17. Moussa, C., N. Ross, P. Jolette, A.J. MacFarlane. Altered folate metabolism modifies cell proliferation and progesterone secretion in human placental choriocarcinoma JEG-3 cells. Br J Nutr 114(6): 844-52. 2015.

  18. Aarabi, M., M.C. San Gabriel, D. Chan, N.A. Behan, M. Caron, T. Pastinen, G. Bourque, A.J. MacFarlane, A. Zini, J. Trasler. High dose folic acid supplementation alters the human sperm methylome and is influenced by the MTHFR C677T polymorphism. Hum Mol Genet 24(22): 6301-13. 2015.

  19. Husseini, M., G.S. Wang, C. Patrick, J.A. Crookshank, A.J. MacFarlane, J.A. Noel, A. Strom, F.W. Scott. Heme oxygenase-1 induction prevents autoimmune diabetes in association with pancreatic recruitment of M2-like macrophages, mesenchymal cells, and fibrocytes. Endocrinology 156(11): 3937-49. 2015.

  20. MacFarlane, A.J., N.A. Behan, M.S. Field, A. Williams, P.J. Stover, C.L. Yauk. Dietary folic acid protects against genotoxicity in the red blood cells of mice. Mutat Res 779: 105–111. 2015.

  21. Stover P.J., A.J. MacFarlane, M.S. Field. Bringing clarity to the role of MTHFR variants in neural tube defect prevention. Am J Clin Nutr 101: 1111-1112. 2015.

  22. Zinck, J.W.R., M. de Groh, A.J. MacFarlane. Genetic modifiers of folate, vitamin B-12, and homocysteine status in a cross-sectional study of the Canadian population. Am J Clin Nutr 101: 1295-1304. 2015.

  23. Wilson RD; Genetics Committee, R.D. Wilson, F. Audibert, J.A. Brock, J. Carroll, L. Cartier, A. Gagnon, J.A. Johnson, S. Langlois, L. Murphy-Kaulbeck, N. Okun, M. Pastuck; Special Contributors, P. Deb-Rinker, L. Dodds, J.A. Leon, H. Lowel, W. Luo, A. MacFarlane, R. McMillan, A. Moore, W. Mundle, D. O'Connor, J. Ray, M. Van den Hof Pre-conception Folic Acid and Multivitamin Supplementation for the Primary and Secondary Prevention of Neural Tube Defects and Other Folic Acid-Sensitive Congenital Anomalies. J Obstet Gynaecol Can 37(6):534–552. 2015.

  24. Washburn, S.E., M.A. Caudill, O. Malysheva, A.J. MacFarlane, N.A. Behan, B. Harnett, L. MacMillan, T. Pongnopparat, J.T. Brosnan, M.E. Brosnan. Formate metabolism in the fetal and neonatal sheep. Am J Physiol – Endocrinol Metab 308(10):E921-7. 2015.

  25. Morrow, G.P., L. MacMillan, S.G. Lamarre, S.K.Young, A.J. MacFarlane, M.E. Brosnan, and J.T. Brosnan. In vivo kinetics of formate metabolism in folate-deficient and folate-replete rats. J Biol Chem

  26. Zinck, J.W.R., and A.J. MacFarlane. Approaches for the identification of genetic modifiers of nutrient dependent phenotypes: Examples from folate. Front Nutr 1(8):1-10. 2014.

  27. Shi, Y., M. de Groh and A.J. MacFarlane. Sociodemographic and lifestyle factors associated with folate status among non-supplement-consuming Canadian women of child-bearing age. Can J Public Health 105(3):e166-e171. 2014.

  28. MacFarlane, A.J., Y. Shi and L.S. Greene-Finestone. High dose compared to low dose vitamin B12 supplement use is not associated with higher vitamin B12 status in children, adolescents and older adults. J Nutr 144(6):915-20. 2014.

  29. MacFarlane, A.J., M.F. McEntee, P.J. Stover. Azoxymethane-induced colon carcinogenesis in mice occurs independently of de novo thymidylate synthesis capacity. J Nutr 144(4):419-24. 2014.

  30. Swayne, B.G., A. Kawata, N.A. Behan, A. Williams, M.G. Wade, A.J. MacFarlane, C.L. Yauk. Investigating the effects of dietary folic acid on sperm count and integrity. Mutat Res 737(1-2): 1-7. 2012.

  31. MacFarlane, A.J., N.A. Behan, F. Matias, J. Green, D. Caldwell, S.P.J. Brooks. Dietary folate does not significantly affect the intestinal microbiome, inflammation, or tumorigenesis in AOM-DSS treated mice. Br J Nutr 5: 1-9. 2012.

  32. Koziol A.G., E. Loit, M.S. McNulty, A.J. MacFarlane, F.W. Scott, I. Altosaar. Globulin-3 storage proteins in wheat embryos are cleaved post-translationally, as shown by mass spectrometry. BMC Res Notes 5:385. 2012

  33. Swayne B.G., N.A. Behan, A. Williams, P.J. Stover, C.L. Yauk, A.J. MacFarlane. Supplemental dietary folic acid has no effect on chromosome damage in erythrocyte progenitor cells of mice. J Nutr 142(5): 813-7. 2012.

  34. MacFarlane, A.J., D.A. Anderson, P. Flodby, C.A. Perry, R.H. Allen, S.P. Stabler, P.J. Stover. Nuclear localization of the de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA. J Biol Chem 286(51): 44015-22. 2011.

  35. MacFarlane, A.J., L. Greene-Finestone, Y. Shi. Vitamin B12 and homocysteine status in a folate-replete population: Results from the Canadian Health Measures Survey. Am J Clin Nutr 94(4): 1079-87. 2011.

  36. Sonier, B., A. Strom, G.-S. Wang, C. Patrick, J. A. Crookshank, M. Mojibian, A.J. MacFarlane, F.W. Scott. Antibodies from a patient with type 1 diabetes and celiac disease bind to macrophages that express the scavenger receptor CD163. Can J Gastroenterol 25(6):327-29. 2011.

  37. MacFarlane, A.J., C.A. Perry, M.F. McEntee, D.M. Lin, P.J. Stover. Mthfd1 is a modifier of chemically-induced intestinal carcinogenesis. Carcinogenesis 32(3):427-33. 2011.

  38. MacFarlane, A.J., C.A. Perry, M.F. McEntee, D.M. Lin, P.J. Stover. Shmt1 heterozygosity impairs folate-dependent thymidylate synthesis capacity and modifies Apcmin-mediated intestinal cancer risk in mice. Cancer Res 71(6):2098-107. 2011.

  39. MacFarlane, A.J., A. Strom, F.W.Scott. Epigenetics – Deciphering how environmental factors may modify autoimmune type 1 diabetes. Mamm Genome 20(9-10):624-32. 2009.

  40. MacFarlane, A.J., C.A. Perry, H.H. Girnary, R.H. Allen, S.P. Stabler, P.J. Stover. Mthfd1 is an essential gene in mice and alters biomarkers of impaired one-carbon metabolism. J Biol Chem 284(3): 1533-39. 2009.

  41. Loit, E., C. Melnyk, A.J. MacFarlane, F.W. Scott, I. Altosaar. Identification of three wheat globulin genes by screening a T. aestivum BAC genomic library with cDNA from a diabetes-associated globulin. BMC Plant Biol 9: 93. 2009.

  42. Stover, P.J., A. J. MacFarlane. Mouse models to elucidate mechanisms of folate-related cancer pathologies. Nutr Rev 66(Suppl. 1): S54-S58. 2008.

  43. MacFarlane, A.J., X. Liu, C.A. Perry, P. Flodby, R.H. Allen, S.P. Stabler, P.J. Stover. Cytoplasmic serine hydroxymethyltransferase regulates homocysteine remethylation but is not essential in mice. J Biol Chem 283(38): 25846-53. 2008.

  44. MacFarlane, A.J., P.J. Stover. Convergence of genetic, nutritional and inflammatory factors in gastrointestinal cancers. Nutr Rev 65 (12 Pt 2): S157-66. 2007.

  45. Mojibian, M., H. Chakir, A.J. MacFarlane, D. Lefebvre, J.R. Webb, C. Touchie, J. Karsh, J. Crookshank, F.W. Scott. Immune reactivity to a Glb1 homologue in a highly wheat sensitive patient with type 1 diabetes and celiac disease. Diabetes Care 29: 1108-10. 2006.

  46. MacFarlane A.J., K.M. Burghardt, J. Kelly, T. Simell, O. Simell, I. Altosaar, F.W. Scott. A type 1 diabetes-related protein from wheat (Triticum aestivum); cDNA clone of a wheat storage globulin, Glb1, linked to islet damage. J Biol Chem 278 (1): 54-63. 2003.

  47. MacFarlane, A.J., D.L. Sutherland, T.R. Goff, K.M. Gilmour. In vivo photostabilization of tetracycline hydrochloride by reduced glutathione for use as an ecological marker in Salmo salar. Aquaculture 213 (1-4): 253-63. 2002.

    Book chapters and government reports

  48. MacFarlane, A.J. and Stover, P.J.  Gastrointestinal Disorders: Overview. In, Encyclopedia of Public Health.  International Encyclopedia of Public Health Second Edition. S. Quah, ed. Elsevier, Amsterdam, The Netherlands. Vol. 3 pp. 9-19. 2016.

  49. MacFarlane, A.J., and P.J. Stover. Gastrointestinal Disorders: Overview. In, Reference Module in Biomedical Sciences. Elsevier, Waltham, MA. 2014.

  50. Van Den Hof, M., A.J. MacFarlane, W. Luo. Primary prevention: Modifiable risk factors. In, Congenital Anomalies Surveillance Report, 2013. Public Health Agency of Canada, Ottawa, ON. 2013.

  51. MacFarlane, A.J. Epigenetic epidemiology of Type 1 diabetes. In, Epigenetic Epidemiology. K.B. Michels, ed. Springer Publishing, New York, NY. 2012.

Expertise

Affiliations

2010 - present          Adjunct Professor, Dept. Biology, Carleton University

2009 - present          Adjunct Professor, Dept. Biochemistry, Microbiology and Immunology, University of Ottawa

Language

English
French