Researcher

Title

• Full Professor, Departments of Pediatrics and Pharmacology, Université de Montréal (2011).

• Postdoctoral Fellow, CHU Sainte-Justine Research Center, Charles Bruneau Cancer Center, Montreal, 1995-1998.
• Postdoctoral Fellow, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, 1992-1994.
• PhD in Molecular Biology, University of Belgrade, Yougoslavia, 1987-1991.
• MSc in Medical Genetics, University of Belgrade, 1984-1986.
• Medical training, License, University of Belgrade, 1982-1984.
• MD, University of Belgrade, 1977-1982.

The research program of Krajinovic group revolves around three major themes: 1. Pharmacogenomics of acute lymphoblastic leukemia (ALL), 2. Pharmacogenomics of hematopoietic stem cell transplantation (HSCT), and 3. Innovative approaches in the diagnosis, prognosis, and treatment of childhood cancer.

ALL is the most common cancer in children. Despite significant improvements in diagnosis and treatment over the past few decades, refractory and relapsed ALL remains the leading cause of disease-related mortality in children. Additionally, the multiple therapies required for treating ALL result in significant adverse drug reactions (ADRs), contributing to both early morbidity and mortality, as well as long-term complications. The goal of this pharmacogenomics program is to identify genetic variants that modulate patients' sensitivity to treatment, thereby predicting a higher risk of adverse drug effects or lower response rates. This ultimately translates into individualized drug dose adjustments and better risk-adapted therapies. Analyses of candidate genes or whole exome sequencing data performed in Krajinovic lab have identified several pharmacogenetic markers associated with disease relapse and ADRs, occurring either during treatment or as late effects, providing pioneering data in ALL pharmacogenetics. To understand the mechanisms by which genetic variants influence treatment outcomes, association analyses are complemented by functional studies.

Similar analyses are conducted in patients undergoing HSCT, identifying novel genetic variants associated with HSCT complications. This research is crucial for individualizing drug treatment prior to HSCT and understanding HSCT genetics.

Currently, she aims to develop prediction models, drug dose adjustments, or novel prophylactic treatments tailored by genetic data to adjust chemotherapy for individual patients and mitigate its toxicity.

Dr. Krajinovic has also developed a complementary approach based on the analysis of microDNA, a novel type of circular extrachromosomal DNA. Her group has demonstrated that microDNA appears non-randomly, suggesting it may reflect specific genomic alterations induced by cancer, making it a potential diagnostic and prognostic biomarker. Its circular structure makes microDNA resistant to enzymes present in liquid biopsies, enhancing its suitability for analysis in these samples. She is currently evaluating its potential to predict unfavorable outcomes in leukemia patients.

• genetics
• pharmacogenetics
•  association analyses
• functional studies
• molecular biology
• microDNA

Career Summary

Maja Krajinovic obtained her medical degree from the University of Belgrade. She holds a master's degree in human genetics and a PhD in molecular biology. She completed postdoctoral training in the fields of human genetics and cancer genetics (Center for Genetic Engineering and Biotechnology, Trieste, Italy, and the Research Center at CHU Sainte-Justine). Since 2000, she has been a researcher at the Centre de recherche Azrieli du CHU Sainte-Justine leading pharmacogenomics research lab, and a professor at the Université de Montréal. Since 2011, she has been a full professor in the departments of Pediatrics and Pharmacology/Physiology at the Université de Montréal. She is responsible for several pharmacogenetics courses that she teaches at the Université de Montréal.

Awards and Distinctions

• National Researcher, Fonds de la recherche en santé du Québec (FRSQ), 2007-2011.
• Senior Research Scholar, FRSQ, 2003-2007.
• Junior 2 Research Scholar, FRSQ, 2001-2003.
• Bourse Relève 2000, Faculty of Medicine, University of Montreal, 2000-2001.
• Postdoctoral Fellowship, Fondation Centre de cancérologie Charles-Bruneau, 1995-1998.
• Postdoctoral Fellowship, Telethon, Italy, 1992-1994.

Presentations

• Genetic predictors of asparaginase toxicity in childhood ALL" (chair of the session: Safety and Efficacy in Cancer Pharmacology). Safety Pharmacology Society and Canadian Society of Pharmacology and Therapeutics (SPS and CSPT), 2022 Joint Annual Meeting, Montreal, September 11-14
• Common germline variants and toxicity" 2nd CLEAR (Childhood Leukemia Early Adverse Reaction) Conference, Comwell Borupgaard, Denmark, May 9-11, 2019
• Pharmacogenomics in Pediatric Hemato-Oncology" The FEAM (Federation of European Academies of Medicine) Conference on Precision Medicine and Personalized Health, Geneva, Switzerland, September 28, 2018
• Polymorphisms of the asparaginase pathway and asparaginase related toxicity in children with acute lymphoblastic leukemia, Precision Medicine: Personal Genomes & Pharmacogenomics Cold Spring Harbor Laboratory, NY, November, 2013
• Pharmacogenetics of childhood leukemia" IXth World Conference on Clinical Pharmacology and Therapeutics - CPT2008 July 27 - August 1, 2008, Québec City (chair of the session: cancer pharmacogenetics)

Publications

1. Petrykey K, Lippé S, Sultan S, Robaey P, Drouin S, Affret-Bertout L, Beaulieu P, St-Onge P, Baedke JL, Yasui Y, Hudson MM, Laverdière C, Sinnett D, Krajinovic M (2024). Genetic factors and long-term treatment-related neurocognitive deficits, anxiety, and depression in childhood leukemia survivors: an exome-wide association study. Cancer Epidemiol Biomarkers Prev. 33(2):234-243.
2. Abaji, R. Roux, V. Yssaad, IR. Kalegari, P. Gagné, V. Gioia, R. Ferbeyre, G. Beauséjour, C. Krajinovic, M. (2022). Characterization of the impact of MYBBP1A gene and rs3809849 on asparaginase sensitivity and cellular functions. Pharmacogenomics. 23(7):415-430
3. Ansari M, Petrykey K, Rezgui MA, Del Vecchio V, Cortyl J, Ameur M, Nava T, Beaulieu P, St-Onge P, Mlakar SJ, Uppugunduri CRS, Théoret Y, Bartelink IH, Boelens JJ, Bredius RGM, Dalle JH, Lewis V, Kangarloo BS, Corbacioglu S, Sinnett D, Bittencourt H, Krajinovic M. (2021) Genetic susceptibility to acute graft versus host disease in pediatric patients undergoing HSCT. Bone Marrow Transplant. 6(11):2697-2704
4. Shalmiev A, Nadeau G, Aaron M, Ouimet-Grennan E, Drouin S, Bertout L, Beaulieu P, St-Onge P, Veilleux LN, Rauch F, Rezgui A, Petrykey K, Laverdière C, Sinnett D, Alos N, Krajinovic M. (2022) Genetic factors contributing to late adverse musculoskeletal effects in childhood acute lymphoblastic leukemia survivors. Pharmacogenomics J. 22(1):19-24. 
5. Gagné V, St-Onge P, Beaulieu P, Laverdière C, Leclerc JM, Tran TH, Sallan SE, Neuberg D, Silverman LB, Sinnett D and Krajinovic M*. (2020). HLA DRB1*07:01, DQA1*02:01 and DQB1*02:02 alleles are associated with asparaginase hypersensitivity in childhood acute lymphoblastic leukemia: A report from the Dana-Farber Cancer Institute Consortium. Pharmacogenomics. 21(8):541-547
6. R Abaji, F Ceppi, S Patel, V Gagné, C J Xu, J-F Spinella, A Colombini, R Parasole, B Buldini, G Basso, V Conter, G Cazzaniga, J-M Leclerc, C Laverdière, D Sinnett, and M Krajinovic* (2018): Genetic risk factors for VIPN in childhood acute lymphoblastic leukemia patients identified using whole-exome sequencing Pharmacogenomics (19(15):1181-1193)
7. P Mehanna, V Gagné, M Lajoie, J-F Spinella, P St-Onge, D Sinnett, I Brukner, M Krajinovic (2017): Characterization of the microDNA through the response to chemotherapeutics in lymphoblastoid cell lines PLOS One 12(9):e0184365.
8. Ben Tanfous M, Sharif-Askari B, Ceppi F, Laaribi H Gagné V, Rousseau J Labuda M, Silverman LB,  Sallan SE, Neuberg D, Kutok JL, Sinnett D, Laverdière C and Krajinovic M  (2015) Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia Clin Cancer Res 21:329-34
9. Rousseau J, Gagné V, Labuda M, Beaubois C, Sinnett D, Laverdière C, Moghrabi A, Sallan SE, Silverman LB, Neuberg D, Kutok JL, and Krajinovic M (2011) The ATF5 polymorphisms influence ATF function and the response to treatment in patients with childhood acute lymphoblastic leukemia. Blood. 118:5883-90
10. Krajinovic M, Costea I and Chiasson S (2002) Polymorphism of the thymidylate synthase gene and outcome of acute lymphoblastic leukemia. Lancet  359:1033-1034.