Research

For our research, we use a systems-wide approach to analyze samples from individual patients diagnosed with a hematological malignancy.

By combining genomic, transcriptomic, proteomic and functional ex vivo drug sensitivity testing of the patient’s tumor cells and comparing these data to that of normal cells, we get a broad view of genomic and phenotypic changes that have occurred in the tumor and which could potentially be therapeutically targeted. In addition, we analyze samples acquired at different stages of the patient’s disease (e.g. diagnosis, during treatment response and relapse) for better insight of disease progression mechanisms and understanding the impact of therapy on the patient’s tumor. Working closely with the FIMM Technology Centre and our collaborators, we quickly return our results to the clinic to maximize the amount of data available for guiding treatment decision of patients with relapsed or refractory disease.

Projects

Acute leukemias

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. However, the standard of care has remained unchanged for the past 30 years. Approximately 50% of AML patients will relapse, at which point there are few treatment options, rapid disease progression and short survival. Recent large-scale genomic studies have shown that AML is comprised of several different diseases, each with separate driver events, and in need of individualized treatment strategies. Deep molecular profiling of AML patient samples combined with functional assessment and clinical outcome data provides us with a wealth of information that we can use to identify novel treatments and indicators of response in addition to understanding the impact of genomic changes on treatment response.

Acute lymphoblastic leukemia (ALL) is an aggressive hematological disease arising from accumulation of immature lymphoid cells in the bone marrow. Long-term survival of adult ALL patients remain modest with 40% of patients surviving five years or longer. Despite improved survival rate in childhood ALL, there is need for effective and less toxic treatment strategies that require pre-clinical evaluation before clinical trials. By using flow cytometry-based drug sensitivity and resistance testing assay, we investigate sub-population specific drug responses and aim to identify novel treatment strategies for high-risk pediatric and adult ALL. Together with molecular profiling on bulk and single-cell fractions, the goal is to facilitate development ALL patient care in the future.

Multiple myeloma

Several new drugs have been approved for the treatment of multiple myeloma, extending the lives of many patients. However, the disease is still considered incurable, as patients will often suffer from successive relapses and finally refractory disease. By applying our systems medicine approach to myeloma, we can stratify patients based on their ex vivo drug sensitivity profile, identify novel treatments for relapsed/refractory and high-risk patients, and look for new targets for therapeutic development.