Digital Public Defence: Laure Isabelle Piechaczyk
M.Sc Laure Isabelle Piechaczyk at Institute of Basic Medical Sciences will be defending the thesis “Identifying new avenues for leukemia treatment using genomewide CRISPR/Cas9 and ex vivo drug sensitivity screens” for the degree of PhD (Philosophiae Doctor).
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Digital Trial Lecture – time and place
- First opponent: Research Group Leader Suvi-Katri Leivonen, University of Helsinki
- Second opponent: Research Leader Kristine Sahlberg, Drammen Hospital, Vestre Viken Hospital Trust
- Third member and chair of the evaluation committee: Associate Professor Tor Erik Rusten, University of Oslo
Chair of the Defence
Professor Valeria Vitelli, University of Oslo
Research Group Leader Jorrit Enserink, Oslo University Hospital
Leukemia includes a group of cancers starting in blood-forming tissues and is characterized by aberrant expansion of immature white blood cells. While treatment of certain forms of leukemia has seen major improvement during the past decades, many leukemia patients do not benefit fully from these therapies.
Treatment of Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia typically includes tyrosine kinase inhibitors (TKIs). While implementation of TKIs in treatment of these patients has strongly improved their prognosis, a substantial number of Ph+ ALL patients and a fraction of CML patients ultimately develop resistance. We performed a genome-wide CRISPR/Cas9 screen to gain insight in the mechanisms that underlie the sensitivity and resistance to TKIs. Our data revealed that deletion of key repressors of mTOR activity increased resistance to a tyrosine kinase inhibitor. We also provide evidence that epigenetic reprogramming of cells might serve as a mechanism for adaptation to tyrosine kinase inhibition.
In a parallel approach, we performed ex vivo drug sensitivity screening of Acute Myeloid Leukemia (AML) patient blast cells to identify compounds that may serve as candidates for drug repurposing. We found that drug sensitivity profiles of the group of AML patients showed a high degree of heterogeneity, which suggests that certain subtypes of AML might respond specifically to different drugs. For example, we identified several drugs that may selectively target cells derived from FLT3-ITD+ AML patients, including HSP90 inhibitors.
Contact the research support staff.