Kaarina Kowalec

Kaarina Kowalec

Affiliated to Research
Visiting address: Nobels väg 12a, 17165 Solna
Postal address: C8 Medicinsk epidemiologi och biostatistik, C8 MEB I Lu Projektgrupp, 171 77 Stockholm
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About me

  • I am a tenure-track Assistant Professor position at the Rady Faculty of Health Sciences at University of Manitoba and hold an Affiliated Research position at the Karolinska Institutet. My research aims to identify precision medicine approaches to neurological diseases and psychiatric disorders. I have received funding from the US Department of Defense, US NIMH and the Consortium of Multiple Sclerosis Centres. During my postdoctoral and PhD studies, I held fellowships from the European Commission (Horizon-2020), and the Canadian Institutes of Health Research (CIHR), including the Marie Skłodowska-Curie Actions-Horizon 2020 European Fellowship (€180K) and the Government of Canada Banting Fellowship, with over 20 awards during my PhD alone, totalling over $960K in personal salary awards, and $1.8M in peer-reviewed operating and team grants. From 2017-19, I was a Postdoctoral researcher at the Karolinska Institute with Professor Patrick Sullivan and the KI-Psychiatric Genomics Institute to harness my collaborative, problem-solving abilities that I have developed during my doctoral training and apply them to the intricate issues faced today by the psychiatric community. My projects involved utilizing the Swedish National Register data, the Sweden Schizophrenia Study, and other psychiatric cohort studies. * Marie Skłodowska-Curie Actions European Fellowship (€185, 000, 2018-2020) - Overall score = 96.6% * CIHR Fellowship ($100, 000 CAD, 2018-2020) - Declined * Canadian Society for Pharmacology & Therapeutics Ken Piafsky Trainee Award for Best Presentation (2016) * Multiple Sclerosis Society of Canada, PhD studentship (2014) * University of British Columbia, Faculty of Medicine Graduate Award (2014 * University of British Columbia, Faculty of Medicine Graduate Award (2013 * CIHR Drug Safety and Effectiveness Cross-Disciplinary Training Program (2013) * Multiple Sclerosis Society of Canada, PhD studentship (2013) * University of British Columbia, College for Interdisciplinary Studies Graduate Award (2012) * CIHR Banting and Best Canada Graduate Scholarship (2011-2014) * CIHR Doctoral Research Award (Clinical Research) (2011-14
  • Declined) * CIHR Doctoral Research Award (Digestive Health, Small Health Organization Partnership Program) (2011-14
  • Declined) * University of British Columbia, 4-YF Fellowship (2011-14
  • Declined) * University of British Columbia, College for Interdisciplinary Studies Graduate Award (2011) * Multiple Sclerosis Society of Canada, PhD studentship (2011
  • Declined) * Manitoba Graduate Scholarship (2008-2010) * University of Manitoba Graduate Fellowship (2008-2010
  • Declined) * Postdoc - Karolinska Institutet 2019 (Psychiatric genetics and epidemiology) * Postdoc - University of British Columba, 2017 (Epidemiology) * PhD - University of British Columba, 2016 (Genomics, Epidemiology) * MSc - University of Manitoba, 2011 (Viral hepatitis, genomics) * BSc (Hons.) - University of Manitoba, 2008 (Microbiology)

Research

  • *Current research:* /*Theme 1: Epidemiology and genomics of poor outcomes in schizophrenia, depression, and other psychiatric disorders*/ Schizophrenia (SCZ) is one of the top 15 leading causes of disability worldwide, with the average number of life years lost ~30 years. Those with SCZ are at 15-25 times higher risk for suicide, compared to the general population. It is currently estimated that ~200, 000 Canadians have SCZ. In 2004, the direct healthcare and non-healthcare costs related to SCZ in Canada were estimated at >$2B, and when considering additional losses, resulted in a total cost estimate of $6.85B. Features associated with poor outcomes in SCZ include childhood adversities (e.g. neglect), family history of psychiatric disorders, and SCZ genomic burden (the weighted sum of the number of SCZ genetic risk variants within each individual). There are currently no means of predicting, at first clinical presentation, who will experience a poor outcome in SCZ. Our overall goal is early detection of those at high risk for poor outcomes in SCZ, thereby triggering logical and effective interventions to mitigate the personal, social, and societal costs associated with severe SCZ. Our overarching translational goal is to develop valid and clinically useful models that predict crucial clinical outcomes for psychiatry and to implement the predictive models on a provincial and national scale. /Projects:/ 1) Investigating the association between accelerated DNA methylation age and mortality in SCZ. This work is published in /*Translational Psychiatry [1].*/ 2) Using population-based Swedish National register data and extensive genomic data to examine treatment resistance in schizophrenia (published in /*Molecular Psychiatry [2]*/).​​ 3) Investigating the role of genetic variation in association with specific and all cause mortality in schizophrenia. This work is published in /*Translation Psychiatry [3]*/. 4) A summary of the genetic advances in schizophrenia, published in /*Psychological Medicine*/ [4]. /*Theme 2: Epidemiology and genomics of poor outcomes in multiple sclerosis (MS) and other ch**ronic immunoinflammatory diseases*/ The prevention of poor outcomes, such as serious adverse drug reactions associated with MS therapies or the development of psychiatric disorders, is essential for those with MS and other chronic immunoinflammatory diseases. Currently, there are few clinically useful predictors of poor outcomes in MS. Variability in the genes that underscore drug biotransformation may be the key to identifying and predicting who is at greatest risk of serious adverse drug reactions and likewise, investigating the genes that underlie polygenic traits like psychiatric disorders, may also be important in investigating those at greatest risk for a psychiatric disorder. Findings from our cutting-edge work (published in /Nature Genetics [5]/, /Neurology [6]/, /BMJ Open [7]/, /Expert Opinion in Drug Safety [8]//, /and /MS and Related Disorders [9]/) could improve outcomes in MS and contribute to the future development of precision medicine approaches to MS and other autoimmune diseases. /Projects:/ 1) Genomic variants associated with DMF induced lymphopenia in MS [GenDMF-MS]: Seeking to predict and ultimately prevent adverse drug reactions in people with MS. An international pharmacogenomic investigation of lymphopenia due to dimethyl fumarate in multiple sclerosis, funded by the National MS Society [10]. The protocol for this work can be found here [11]. 2) Understanding psychiatric comorbidity in chronic immunoinflammatory diseases using genomics: Chronic immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease, MS, and rheumatoid arthritis, affect around 5% of Canadians. These conditions have a particularly high prevalence in Canada and are characterised by acute exacerbations and progressive disability. Management of these diseases involves immunomodulatory and immunosuppressive drug therapies, although each disease may require unique drugs. The treatment goal for each disease is remission as these diseases are incurable. The impact of psychiatric comorbidities, such as anxiety and depression are substantial in those with an IMID. The incidence rate ratios of depression (1.71, 95%CI: 1.64-1.79) and anxiety (1.34
  • 95%CI: 1.29-1.40) are increased in those with an IMID, compared to those without an IMID and may suggest a common biological basis for psychiatric comorbidity and the IMID (Marrie RA, et al. /J Psychosom Res/. 2017
  • 101:17-23). These psychiatric comorbidities are also under-diagnosed and under-treated in the context of an IMID and identifying biomarkers of their comorbidity may enhance their identification leading to earlier treatment. This work has been funded by the US Department of Defense and is currently ongoing. 3) Understanding factors associated with substance use disorder in those with inflammatory bowel disease and rheumatoid arthritis in Manitoba. This project is now published in Inflammatory Bowel Diseases [12] and ACR Open Rheumatology [13]. *Publications* * *Kowalec K*, Lu Y, Song J, Dalman C, Hultman C, Larsson H, Lichtenstein P, Sullivan PF. (2021) The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study. /Translational Psychiatry, /2021 Mar 15
  • 11(1):163. * Harroud A, Marrie RA, Fitzgerald K, Salter A, Lu Y, Patel M, *Kowalec K*. (2021) Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis. /Mult Scler Journal/, Accepted 14 January 2021. * Legge SE, Santoro ML, Periyasamy S, Okewole A, Arsalan A, * Kowalec K. *(2021) Genetic architecture of schizophrenia: a review of major advancements. /Psychological Medicine, /Feb 8: 1-10. * *Kowalec K*, Carney H, Patel M, Hitchon C, Bolton JM, Patten SB, Graff LA, Bernstein CN, Peschken C, Marrie RA, for the CIHR Team in Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease*.* (2021). Prevalence and risk factors of substance use disorders in rheumatoid arthritis. /ACR Open Rheumatology, /Accepted 9 August 2021. * Johnson D, Wilke M, Lyle S, *Kowalec K*, Jorgensen A, Wright GEB, Drögemöller BD. A systematic review and analysis of the use of polygenic scores in pharmacogenomics. /Clinical Pharmacology and Therapeutic/s. Accepted December 2021. * Nguyen TD, Harder A, Xiong Y, *Kowalec* *K*, Hägg S, Cai N, Kuja-Halkola R, Dalman C, Sullivan PF, Lu Y. Genetic* *heterogeneity, and subtypes of major depression. /Molecular Psychiatry/, 19 Nov 2021. * Pardiñas AF, … (76 other authors), *Kowalec K*, Sullivan PF, Murray RM, Owen MJ, MacCabe JH, O’Donovan MC, Walters JTR. Interaction testing and polygenic risk scoring to estimate the contribution of common genetic variants to treatment resistance in schizophrenia. /JAMA Psychiatry/, epub 12 Jan 2022. * Hannon E, Dempster EL, Mansell G, Burrage J, Bass N, Bohlken MM, Corvin A, Curtis CJ, Dempster D, DiForta M, Dinan TG, Donohoe G, Gaughran F, Gill M, Gillespie A, Gunasinghe C, Hulshoff HE, Hultman C, Johansson V, Kahn RS, Kaprio J, Kenis G, *Kowalec K*, MacCabe J, McDonald C, McQuillin A, Morris DW, Murphy KC, Mustard C, Nenadic I, O’Donovan MC, Quattrone D, Richards AL, Rutten BPF, St-Clair D, Therman S, Toulopoulou T, Van Os J, Waddington JL, Wellcome Trust Case Control Consortium 2, CREeTable AR consortium, Sullivan PF, Vassos E, Breen G, Collier DA, Murray R, Schalkwyk LS, Mill J. (2021). Large-scale analysis of DNA methylation identifies cellular alterations in blood from psychosis patients and molecular biomarkers of treatment-resistant schizophrenia. eLife, 10:e58430. * Carney H, Marrie RA, Bolton JM, Patten SB, Graff LA, Bernstein CN, *Kowalec K.* (2021). Prevalence and risk factors of substance use disorders in inflammatory bowel disease. /Inflammatory Bowel Diseases/, 27(1):58-64. * Salter A, *Kowalec K*, Fitzgerald K, Cutter G, Marrie RA. (2020). Comorbidity is associated with disease activity in MS: Findings from the CombiRx Trial. /Neurology, /95(5): e446-e456. * *Kowalec K*, Lu Y, Sariaslan A, Song J, Ploner A, Dalman C, Hultman C, Larsson H, Lichtenstein P, Sullivan PF. (2019) Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: A Swedish National register and genomic study. /Molecular Psychiatry/ Nov 12. doi: 10.1038/s41380-019-0575-1. * **Kowalec K*, Hannon E, Mansell G, Burrage J, Ori APS, Ophoff RA, Mill J, Sullivan PF. (2019). Methylation age does not predict mortality in schizophrenia. /Translational Psychiatry/, 9(1):157. *Senior Author. * *Kowalec K*, Wright GEB, Drögemöller BI, Aminkeng F, Bhavsar AP, Kingwell E, Yoshida EM, Traboulsee A, Marrie RA, Kremenchutzky M, Campbell TL, Duquette P, Chalasani N, Wadelius M, Hallberg P, Xia Z, De Jager P, Ross CJD, Tremlett H, Carleton BC. (2018) Genome-wide scan identifies novel association with interferon-beta induced liver injury in multiple sclerosis patients. /Nature Genetics/, 50(8):108-1085. * *Kowalec K*, McKay K, Patten S, Fisk J, Evans C, Tremlett H, Marrie RA. (2017) Comorbidity increases the risk of relapse in multiple sclerosis: A prospective study. Neurology, 89(24): 2455. * McCormack M, Gui H, Ingason A, Speed D, Wright GEB, Zhang EJ, Secolin R, Yasuda C, Kwok M, Wolking S, Becker F, Rau S, Avbersek A, Heggeli K, Leu C, Depondt C, Sills GJ, Marson AG, Auce P, Brodie MJ, Francis B, Johnson MR, Koeleman BPC, Striano P, Coppola A, Zara F, Kunz WS, Sander JW, Lerche H, Klein KM, Weckhuysen S, Krenn M, Gudmundsson LJ, Stefánsson K, Krause R, Shear N, Ross CJD, Delanty N
  • EPIGEN Consortium, Pirmohamed M, Carleton BC
  • *Canadian Pharmacogenomics Network for Drug Safety*, Cendes F, Lopes-Cendes I, Liao WP, O'Brien TJ, Sisodiya SM, EpiPGX Consortium, Cherny S, Kwan P, Baum L, International League Against Epilepsy Consortium on Complex Epilepsies, Cavalleri GL. (2018). Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients. Neurology, 90(4): e332. * Kowalec K, Kingwell E, Carruthers R, Marrie RA, Traboulsee A, Bernatsky S, Ross CJD, Carleton B, Tremlett H. (2017) Application of pharmacogenomics to investigate adverse drug reactions to the disease-modifying treatments for multiple sclerosis: a case-control study protocol for dimethyl fumarate induced lymphopenia. BMJ Open, 7(5): e016276. * McKay KA*, *Kowalec K**, Brinkman F, Finlay BB, Horwitz M, Manges AR, Osborne L, Tremlett H. (2016) From bugs to brains: the microbiome in neurological health. MS and Related Disorders, Accepted December 2016. *Shared first author. * Osiowy C, *Kowalec K*, Giles E. (2016). Discordant diagnostic results due to a hepatitis B virus T123A HBsAg mutant. Diag Microbiol Infect Dis, 85(3):328-33. * *Kowalec K*, Kingwell E, Yoshida EM, Marrie RA, Kremenchutzky M, Campbell T, Wadelius M, Carleton BC, Tremlett H. (2014) Characteristics associated with drug induced liver injury from interferon beta in multiple sclerosis patients. Expert Opin Drug Saf, 13(10): 1305-17. * *Kowalec K*, Carleton BC, Tremlett, H. (2013). The potential role of pharmacogenomics in the prevention of serious adverse drug reactions in multiple sclerosis. Mult Scler Rel Dis, 2 (3): 183-192. * *Kowalec K, * Yoshida EM, Traboulsee A, Carleton BC, Tremlett H. (2013). Suspected autoimmune hepatitis and primary biliary cirrhosis unmasked by interferon-beta in a multiple sclerosis patient. Mult Scler Rel Dis, 2 (1): 57-59. * *Kowalec K*, Minuk GY, Børreson M, Simons B, McMahon B, and Osiowy C. (2013). Genetic diversity of hepatitis B virus genotypes B6, D and F among circumpolar indigenous individuals with various clinical outcomes. J Viral Hep, 20 (2): 122-30. * Minuk GY, *Kowalec K*, Caouette S, Larke B. and Osiowy C. (2012). The prevalence and long-term outcome of occult hepatitis B virus infections in community based populations. J Med Virol, 84 (9): 1369-75. * Osiowy C, Kaita K, *Solar K*, and Mendoza K. (2010). Molecular characterization of Hepatitis B virus and a 9-year clinical profile in a patient infected with genotype I. J Med Virol, 82 (6): 942-8. (Published under Solar = Maiden name). [1] https://www.ncbi.nlm.nih.gov/pubmed/31164630 [2] https://www.nature.com/articles/s41380-019-0575-1 [3] https://doi.org/10.1038/s41398-021-01282-1 [4] https://pubmed.ncbi.nlm.nih.gov/33550997/ [5] https://www.ncbi.nlm.nih.gov/pubmed/30013178 [6] https://www.ncbi.nlm.nih.gov/pubmed/29117961 [7] https://www.ncbi.nlm.nih.gov/pubmed/28576902 [8] https://www.ncbi.nlm.nih.gov/pubmed/25134421 [9] https://www.ncbi.nlm.nih.gov/pubmed/25877724 [10] https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Research/New-Pilots-for-Fall-2018.pdf [11] https://www.ncbi.nlm.nih.gov/pubmed/28576902 [12] https://academic.oup.com/ibdjournal/advance-article-abstract/doi/10.1093/ibd/izaa014/5728525 [13] https://onlinelibrary.wiley.com/doi/abs/10.1002/acr2.11339

Teaching

  • * 2019-Current: College of Pharmacy, University of Manitoba. Instructor for Principles of Scientific Literature Evaluation and Pharmacogenetics (PHMD2012). * 2012 to 2016: Department of Biochemistry & Molecular Biology, Faculty of Science, University of British Columbia (UBC) - Teaching Assistant for bioc 301: Biochemistry Laboratory. * 2011 to 2012: Biology Program, Faculty of Science, UBC - Laboratory Instructor for BIOL 140: Laboratory Investigations Into the Life Science * 2008 to 2009: Max Rady College of Medicine, Department of Medical Microbiology, University of Manitoba, Problem-Based Learning Facilitator

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