. Mirna El Khatib is a synthetic organic chemist, whose goal is to transition into the area of biomedical imaging with applications in cancer biology. An NHLBI K25 award will help her to accomplish this transition and simultaneously will lead to exploration and development of a new class of imaging probe, namely Membrane-Anchored Probes (MAP) for oxygen. Longitudinal imaging is an indispensible tool for learning about progression of disease and outcomes of therapies. The first step in this proposal is to develop a general approach to membrane-tethered molecular sensors. Membrane-anchored probes (MAP) offer a unique opportunity to longitudinally image concentrations of nutrients and signaling molecules, in this case oxygen, in the immediate environment of the cell. When used in vivo such probes will remain longer in the region of interest, compared to sensors dissolved in the extracellular milieu. The new MAP for oxygen will be applied towards longitudinal oxygen measurements in the niche of transplanted hematopoietic stem cells (HSCs) and leukemic cells (LCs). This will unravel why HSCs choose to localize in specific regions of the bone marrow (BM) and why leukemic stem cells (LSCs) evade death during chemotherapy.
. Membrane-anchored probes (MAP) for longitudinal imaging of extracellular analytes will make up an invaluable new tool for biological research. The aim of this proposal is to develop MAP for oxygen and to study, over extended periods of time, the role of oxygen in the fate of hematopoietic stem cells and leukemic cells in the bone marrow, with the long-term goal to improve the efficacy of chemotherapy in battling leukemia by overcoming leukemic cell resistance. Applying my skills as synthetic organic chemist and combining them with new skill set in both cancer biology and cellular imaging, acquired during the duration of this research project, will help me transition into a biomedical area and mature as an independent investigator.
