Membrane Anchored-Probes for Sensing Analytes at the Cell Surface

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Project Summary. 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.