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Kaarina Kowalec

Kaarina Kowalec

Associated

About me

I am currently a Postdoctoral Researcher with Prof. Patrick Sullivan, Professor of Psychiatric Genetics (Karolinska Institute), and the Yeargan Distinguished Professor in the Department of Genetics and Psychiatry (University of North Carolina at Chapel Hill) at the Karolinska Institute of Psychiatric Genetics Institute. Prof. Sullivan chairs the Coordinating Committee of the Psychiatric Genomics Consortium (PGC) and is a core member of the schizophrenia group. The PGC is a confederation of 900 scientists from 80+ institutions in 25 countries who are Conducting large-scale genomics studies for 11 psychiatric disorders, including schizophrenia.  The overall goal of our research group is to systemically evaluate the epidemiological, molecular, and cellular effects of These loci. The research is highly trans-disciplinary collaborations within the Karolinska Institute, Sweden, Europe, the US, and Australia. Multiple large Data Collection Efforts have been based at MEB, and New Efforts are in progress.

Research description

Current Research:

Project 1: Identifying Clinical, Demographic, & Genomic Risk Factors for Treatment-Resistant Psychiatric Disorders

Approximately 30-60% of those with psychiatric illnesses respond poorly to therapy and may experience devastating effects. Those with treatment-resistant psychiatric disorders have higher mortality, costs, and longer hospitalizations compared to treatment-responders. Schizophrenia (SCZ), major depressive disorder (MDD), bipolar disorder (BIP), and anorexia nervosa (AN) are aetiologically similar, often co-aggregate in families, and have overlapping common variant genetic architectures. These psychiatric disorders (several of which are hierarchically arranged) are at least partly aetiologically similar. These conditions have clinical comorbidity; if one disorder is present, there is substantial risk for one or more other disorders. I am unaware of any systematic assessment of genetic, clinical, and demographic factors associated with treatment-resistance across SCZ, BIP, MDD, and AN simultaneously. Previous studies evaluated single disorders and were limited by small samples and did not consider a range of risk factors.

I am aiming to investigate whether risk factors common to treatment-resistant SCZ, MDD, BIP, or AN exist and I believe that a core treatment-resistant or “clinically severe” cluster of individuals exists across the four psychiatric disorders.

Project 2: Prediction of mortality using DNA methylation age in schizophrenia

DNA methylation levels vary over the course of life. Surprisingly, pre-selected combinations of methylation array probes can be used to estimate “methylation age” (mAge), which usually correlates highly with chronological age. Occasionally, mAge is greater than chronological age, and this difference is a replicated predictor of all-cause mortality. SCZ is associated with significantly higher mortality and decreased life expectancy. We tested the association between mAge and mortality in individuals with SCZ and controls, hypothesizing that mAge predicts subsequent death in SCZ.

 

Past (and on-going) Research:

Epidemiological Investigations Into the Multiple Sclerosis (MS)

My Ph.D. Training focused on the epidemiology and pharmacogenomics of MS with Dr. Helen Tremlett (U. of British Columbia). I defined the prevalence of liver injury due to interferon beta therapy in MS to be approximately 1 in 50 exposed interferon beta, Utilizing a mixed epidemiological approach (Kowalec et al, Exp Opin Drug Saf 2014). More recently, as a Postdoctoral Researcher in the Pharmacoepidemiology of MS Research Group, in a joint study, I evaluated the association between comorbidity and the risk of relapse in a prospective, multicenter study in individuals with MS. This work was recently published in Neurology.

Multi-Omic Studies in MS

My research PhD dissertation Also included the first-ever genome-wide association study for a serious adverse drug reaction in MS for Which The created new collaborations between three countries, encompassing 8 institution. The study findings were clinically relevant and Statistically significant; w ith the identification of a novel biomarker highly associated with the drug reaction. The Corresponding manuscript for this study is currently under going audits. An on-going study that i am affiliated with is  investigating biomarkers of lymphopenia from one of the newly approved MS therapies. Lastly, I am Applying my previous expertise with investigating MS and communicable diseases (Research from my MSc) to research the effects of MS disease-modifying therapies on the gut microbiome in MS.

 

Publications

  • 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).

Teaching portfolio

  • 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
  • 2 008 to 2 009 Max Rady College of Medicine, Department of Medical Microbiology, University of Manitoba, Problem-Based Learning Facilitator

Education

  • PhD - University of British Columba, 2016 (Pharmacogenomics, drug safety)
  • MSc - University of Manitoba, 2011 (Viral hepatitis, genomics)
  • BSc (Hons.) - University of Manitoba, 2008 (Microbiology)

Academic honours, awards and prizes

  • 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)

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