Novel Strategies for Understanding and Treating Fibrous Dysplasia

PROJECT SUMMARY The overall goals of this diversity supplement are to develop the candidate’s background in biological and translational sciences and position her to be a strong candidate for future graduate degree training. The supplement focuses on three main approaches: Didactic research experiences, to provide exposure to a wide

breadth of ground-breaking science; hands-on laboratory experiences, to provide a realistic view of the trials and tribulations of research as well as develop presentation skills and confidence to critically discuss scientific questions; and direct mentoring, to provide tailored tutorials about the scientific process, molecular and cell

biology, and methods for studying genetic diseases of the skeleton. In addition, these sessions will assist with career development and planning. The candidate will work on two aims over the course of two years. These aims are related to the induced pluripotent stem cell (iPSC) work for compound screening in Aim 1 of the parental

R01 grant. Aim 1A: Create a series of isogenic human iPSC lines carrying the GNASR201H or GNASWT gene; Aim 1B: Use genetic modification to understand novel pathway interactions between GNAS and ACVR1 in human iPSCs. The candidate will utilize a series of gene editing strategies we recently developed to carry out these aims.

Together, the research products of this supplement will help address one of the biggest challenges with any iPSC model system – having robust isogenic biological replicates to demonstrate reproducibility and confirm that the pharmacologic approaches are recapitulating the expected biological functions. The lines generated here will be

helpful for the parental Aim 1 by providing these replicates. In addition, these results will provide an opportunity to explore a newly identified potential interaction between the GNAS and ACVR1 pathways. Elucidating these interactions has the potential to find alternate strategic targets that could be used to manage diseases that affect

each pathway. Finally, at the completion of this experience, the candidate will be well positioned as a strong candidate for further training in a graduate program in the sciences.