Research: Cellular development is orchestrated by cell surface proteoglycans. Despite their potential for biomedicine, strategies that harness their functions are limited. This gap is caused by the lack of techniques that recognize their nanoscale complexity. This application outlines the development of chemical strategies to mimic and probe the nanoscale architecture and organization of proteoglycans in cellular development. In two specific aims, we will demonstrate that the techniques developed through this proposal will enable new chemical strategies to control embryonic stem cell differentiation and the regeneration of skeletal muscles. Career Goals and Background. My long-term goal is to become a professor at a major University within US. In this position, I intend to establish a research platform that encompasses the fields of chemistry, glycobiology, and nanoscience to advance biomedicine. The two aspects embedded into the K99/R00 platform will allow me to achieve my goal. Throughout my graduate and postdoctoral career, I have demonstrated my capabilities for interdisciplinary research at the interface of chemistry, nanoscience, and engineering. As a graduate student, I developed peptidomimetics molecules that exhibit antimicrobial or antifreeze activity. These projects have enabled me to be well-versed in chemical biology and biophysical techniques to characterize membranes. As a postdoctoral fellow, I have acquired skills in polymer synthesis and stem cell differentiation. Thus, my academic and research background makes me capable of achieving the goals of this proposal within the specified time frames. Training and Environment: UC San Diego has a superb academic and scientific community that facilitates a highly innovative and collaborative environment, which will promote my scholarship and professional growth. The mentored phase of this Award will allow me to acquire new skills in molecular biology, glycobiology and professional development that will be critical for my transition to an independent career. The proposed scientific training will be conducted with the tutelage of my mentor and co-mentor, Prof. Kamil Godula and Prof. Jeffrey Esko, who are pioneers in glycopolymer technology, molecular biology, and glycobiology. These new skills will be augmented by a mixture of didactic and hands-on laboratory training. I will have direct access to all the necessary components of my research and career development. There is a wealth of professional development activities within UC San Diego that will enable me to become a better grant writer and manager. I have also assembled a world-class mentoring committee who will monitor and advise on my research progress and transition into an independent career.
Cellular development is orchestrated by proteoglycans that facilitate growth factor binding and signaling at the cell surface. Targeting proteoglycans as a strategy to regulate cellular development holds great biomedical promise, but this potential has been hampered by their exquisite structural complexity. This application describes chemical strategies to mimic and harness the nanoscale architecture and organization of proteoglycans, for applications in regenerative medicine and musculoskeletal research.
|Naticchia, Matthew R; Laubach, Logan K; Tota, Ember M et al. (2018) Embryonic Stem Cell Engineering with a Glycomimetic FGF2/BMP4 Co-Receptor Drives Mesodermal Differentiation in a Three-Dimensional Culture. ACS Chem Biol 13:2880-2887|
|Huang, Mia L; Michalak, Austen L; Fisher, Christopher J et al. (2018) Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State. Stem Cells 36:45-54|
|Huang, Mia L; Tota, Ember M; Lucas, Taryn M et al. (2018) Influencing Early Stages of Neuromuscular Junction Formation through Glycocalyx Engineering. ACS Chem Neurosci :|
|Huang, Mia L; Tota, Ember M; Verespy 3rd, Stephen et al. (2018) Glycocalyx Scaffolding to Control Cell Surface Glycan Displays. Curr Protoc Chem Biol 10:e40|
|Huang, Mia L; Purcell, Sean C; Verespy III, Stephen et al. (2017) Glycocalyx scaffolding with synthetic nanoscale glycomaterials. Biomater Sci 5:1537-1540|
|Huang, Mia L; Smith, Raymond A A; Trieger, Greg W et al. (2016) Glycocalyx Remodeling with Glycopolymer-Based Proteoglycan Mimetics. Methods Mol Biol 1367:207-24|