Researcher

Title

• Full Professor, Departments of Pediatrics and Pharmacology, University of Montreal.

• 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 majority of drugs are characterized by pharmacokinetic and pharmacodynamic variability, explaining response variation in patients treated with the standard dose of a medication. Such variability can explain sub-optimal responses to drugs such as adverse reactions or resistance to treatment, indicating a need to identify factors associated with variable drug effects. This will allow the development of individualized treatments with increased efficacy for resistant patients and will reduce drug side effects in patients who respond well.

Based on the hypothesis that the polymorphisms in genes which control drug action (candidate genes), contribute to inter-individual variability in response to medication, we have developed several pharmacogenetics projects. The major goals of these projects are: a) to understand the influence of candidate gene polymorphisms on drug action, protein function and disease outcome; b) to identify polymorphisms that have predictive value to resistance/toxicity patterns; and c) to provide the knowledge that will establish the grounds for personalized drug treatment. One of the pharmacogenetic projects addresses several antitumor drugs used in the treatment of acute lymphoblastic leukemia (ALL). ALL is the most frequent pediatric malignancy still associated with resistance to treatment and drug side effects, in spite of increased survival rates achieved over the last decades.

We are also analyzing three major classes of medications used in the treatment of childhood asthma. In light of the increasing incidence and severity of asthma in children, more accurate use of asthma medication may provide adequate control of asthma early in the disease process (during childhood) thus possibly preventing loss of lung function in adult life. We are also running two pilot projects: pharmacogenetics of valproic acid in patients with idiopathic generalized epilepsy (since 20% of children do not respond to this anti-seizure agent) and pharmacogenetics of busulfan, a key compound in conditioning myeloablative regimens for children undergoing hematopoietic stem cell transplantation. Busulfan has a narrow therapeutic index: high drug exposure leads to increased risk of hepatic veno-occlusive disease, while low drug exposure has been associated with higher risk of disease recurrence and graft failure, requiring therapeutic drug monitoring and drug dose adjustment.

We are also running a complementary project based on the novel technological approach aiming to develop a new generation of nucleic acid probes. These probes should allow discrimination among the targets with high sequence identity.

Pediatric asthma database and biobank of the CHU Sainte-Justine

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.