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DF/HCC members awarded grants amid tight funding environment

Biosynthesis and function of lactosaminyl glycans in hematopoiesis ($18 million)
PI: Robert Sackstein, MD, PhD (BWH)
The central hypothesis of this proposal is that cell surface glycans critically shape formation of marrow niches that sustain HSPCs and dictate lineage fate decisions. Specifically, we wish to elucidate the role(s) of terminal lactosaminyl glycans in regulating myelopoietic and thrombopoietic processes. We seek to obtain fundamental information regarding the stage- and lineage-specific distribution of terminal lactosaminyl glycans on pertinent scaffolds of relevant progenitor cells and the biosynthetic pathway(s) that direct their expression, their structural biology (linkages and branching/multiplicity), their influence(s) on marrow adhesive interactions, and, altogether, their effect(s) on clonogenicity. Moreover, this program will establish new technical resources to interrogate glycan structure and function, and will establish a glycosciences skills development core that will provide training in the background, tools and techniques necessary for the creation of new investigators possessing the requisite knowledge and skills to drive forward the field of translational glycobiology.   

Therapeutic opportunities for pediatric astrocytoma ($8 million)
PI: Rosalind Segal, MD, PhD (DFCI)
The long-term goal of this program is to improve the standard of care for pediatric astrocytomas - the most common brain cancers in children. Towards this end, we will improve our understanding of astrocytoma biology and develop new diagnostic, prognostic and therapeutic tools for these tumors. The significance of the work is that primary cancers of the central nervous system have now surpassed leukemia as the leading cause of cancer-related death in children.

Multidisciplinary structures at vascular cell surfaces ($1.5 million)
PI: Timothy Springer, PhD (CHB)
This Program Project is centered on the structural biology of important molecules in the vascular and blood systems. The Program integrates studies at the atomic and cellular level on cell adhesion and signaling in the vasculature, with the overall aim of accelerating both the acquisition of new knowledge and the development of drugs to treat disease. It is integrated around a multidisciplinary structural biology investigation of molecules of central importance in vascular biology and disease. Most of these molecules are also potential therapeutic targets.  It is an emerging theme in structural biology that more than one structural technique is often required to solve important biological problems; however, structural techniques are so specialized that it is difficult to master more than one. Therefore, close integration of researchers with different expertise is important, and this is exactly what this program is designed to accomplish.