University of Toronto: Fields of study: Nutrition and Toxicology
Univeristy of Toronto: Faculty of Pharmacy
McGill University: Pharmacology and Therapeutics
Eleven and a half years of pharamceutical industry experience in reproductive and developmental toxicology and research and discovery.
The long term goal of our research is to contribute to a greater understanding of the causes and consequences of birth defects and to apply this knowledge to the development of new therapeutic strategies in prevention and treatment.
More specifically we want to understand how environmental influences during gestation may adversely affect health outcome. Clinically, this may be manifest at parturition as an identifiable birth defect, or contrastingly, as a phenotypically normal infant who is predisposed, many decades later, to adult onset diseases. The study of birth defects is a critical health concern with serious social and economic consequences because it has been estimated that between 3-7 % of all infants are born with some form of identifiable anomaly, and moreover, birth defects are the leading cause of infant mortality. Although it has been demonstrated that the in utero environment can influence adult health outcomes, the full extent of its impact is unclear.
The ventricular septation defect (VSD) of the heart is the most common malformation noted clinically and in animal models; however, its aetiology remains unclear. To facilitate the study of this defect we have developed a rat model in which approximately 80% of pups present with VSD at parturition, and it is the primary focus of our laboratory. Using this model we aim to understand the common mechanism of action that allows an array of structurally and pharmacologically diverse chemicals to cause VSD. Interestingly, both clinically and in animal models, most VSD spontaneously repair; however, even in cases where the defect has spontaneously closed or been surgically repaired, patients are more susceptible in later life to non septum-related heart health concerns. Our goal is to understand why this is, and the embryological basis for these differences.
- In Utero Dimethadione Exposure Causes Postnatal Disruption in Cardiac Structure and Function in the Rat. Aasa KL, Purssell E, Adams MA, Ozolinš TR. Toxicol Sci. 2014 Sep 19. pii: kfu190. [Epub ahead of print] PMID: 25239635
- Regulation and control of AP-1 binding activity in embryotoxicity. Ozolinš TR. Methods Mol Biol. 2012;889:291-303. doi: 10.1007/978-1-61779-867-2_18.PMID: 2266967
- Noninvasive high-resolution ultrasound reveals structural and functional deficits in dimethadione-exposed fetal rat hearts in utero. Purssell E, Weston AD, Thomson JJ, Swanson TA, Brown NA, Ozolinš TR. Birth Defects Res B Dev Reprod Toxicol. 2012 Feb;95(1):35-46. doi: 10.1002/bdrb.20339. Epub 2011 Nov 29. PMID: 22127902
- Co-variation in frequency and severity of cardiovascular and skeletal defects in Sprague-Dawley rats after maternal administration of dimethadione, the N-demethylated metabolite of trimethadione. Weston AD, Brown NA, Ozolinš TR.
Birth Defects Res B Dev Reprod Toxicol. 2011 Jun;92(3):206-15. doi: 10.1002/bdrb.20302. Epub 2011 Jun 2. PMID: 21638752
- Not a walk in the park: the ECVAM whole embryo culture model challenged with pharmaceuticals and attempted improvements with random forest design. Thomson J, Johnson K, Chapin R, Stedman D, Kumpf S, Ozolinš TR. Birth Defects Res B Dev Reprod Toxicol. 2011 Apr;92(2):111-21. doi: 10.1002/bdrb.20289. Epub 2011 Mar 2. PMID: 21370399
- Cyclophosphamide and the Teratology Society: an awkward marriage. Ozolins TR. Birth Defects Res B Dev Reprod Toxicol. 2010 Aug;89(4):289-99. doi: 10.1002/bdrb.20255. Review. PMID: 20803689
- Analysis of the role of the HIF hydroxylase family members in erythropoiesis. Fisher TS, Lira PD, Stock JL, Perregaux DG, Brissette WH, Ozolins TR, Li B. Biochem Biophys Res Commun. 2009 Oct 30;388(4):683-8. doi: 10.1016/j.bbrc.2009.08.058. Epub 2009 Aug 14. PMID: 19683512
- Defects in embryonic development of EGLN1/PHD2 knockdown transgenic mice are associated with induction of Igfbp in the placenta. Ozolins TR, Fisher TS, Nadeau DM, Stock JL, Klein AS, Milici AJ, Morton D, Wilhelms MB, Brissette WH, Li B. Biochem Biophys Res Commun. 2009 Dec 18;390(3):372-6. doi: 10.1016/j.bbrc.2009.08.057. Epub 2009 Aug 14. PMID: 19683511