Centre for Research on Biomolecular Interactions presents Assist. Prof. Terry Sachlos, Department of Mechanical Engineering, Lassonde School of Engineering, York University

Talk Title: "3D Bone Marrow Niche Engineering for Targeted Cancer Stem Cells Drug Discovery"

Abstract: Acute myeloid leukemia is a fatal blood cancer with approximately 14,300 patients newly diagnosed in North America every year and only 20% of patients expected to survive 5 years after diagnosis. The malignant AML blast cells rapidly overwhelm the bone marrow, disrupting resident hematopoietic stem cells (HSC) and normal blood production and eventually causing death. Treatment involves administration of DNA-binding chemotherapeutic agents which also indiscriminately kill both HSC and progenitors leading to myelosuppression and ultimately drug dose attenuation. Ideally, drugs should specifically target AML while sparing healthy HSC in order to reduce potentially lethal myelosuppression side-effects and extend the dosing period. In this talk, we will discuss the development of a novel pluripotent stem cell screening platform that is used to identify agents that specifically target AML-leukemic stem cells (AML-LSC) while sparing HSC (Sachlos et. al., Cell 2012).  Uniquely, the assay is designed to distinguish and identify agents that induce a differentiation-response in tumour cells while counterscreening for healthy stem cell responses. Following a screen of 2,500 off-patent drugs, this assay led to the discovery of dopamine receptors as a unique therapeutic target on AML-LSC and the identification of thioridazine, an established anti-psychotic agent, as a drug that should be repurposed for AML therapy. Future assay development involving 3D bone marrow niche engineering to screen HSC and AML cells ex vivo will be discussed.

Please join us,

Refreshments will be served.