Glycosaminoglycans (GAGs) contribute to myriad, and very often opposing, functions such as cellular proliferation as well as apoptosis, self-renewal as well as differentiation. Yet, precious little is understood about the exact GAG sequences that induce these functions. Of particular importance to this program project, although GAGs are significant components of the bone marrow (BM) microenvironment, the nuts and bolts of whether GAGs modulate hematopoietic cell fate; whether these interactions are selective/specific; and whether GAG or GAG-like molecules can be harnessed for therapeutic purposes remain poorly understood. This project focuses on elucidating the GAG structure?function relationships of importance to hematopoiesis & thrombopoiesis.
Three aims are proposed including 1) Develop Technology for Elucidation of GAGactomes of Biological Samples, especially Cells and Microenvironment of the Bone Marrow; 2) Employ the Library of Synthetic GAG Mimetics for Modulation of Hematopoietic Outcomes; and 3) Elucidate Specificity and Function of GAG Recognition of Sialyl Transferase ST6Gal-1. The outcomes of these aims will be the precise structure?function relationships in GAGs that induce hematopoietic functions. Specifically with respect to hematopoiesis, the project aims to answer the question of whether GAGs modulate hematopoietic cell fate. If so, are GAG interactions are selective? If selective, can GAG sequences or mimetics of GAGs be harnessed as therapeutics for hematopoietic disorders? Overall, this project contributes knowledge, tools/technology, and therapeutically promising agents in the area of hematopoiesis and thrombopoeisis.