Laboratory for Musculoskeletal Research and Innovation (LMRI)

17β-estradiol can promote the growth and development of several laryngeal carcinoma cell lines. However, due to the variability in estrogen receptor expression, laryngeal cancer is not considered estrogen-responsive cancer. ERα36 has been shown to mediate rapid, non-genomic, membrane-associated effects of 17β-estradiol in several cancer cell lines, including triple-negative HCC38 breast cancer cells and estrogen receptor-positive MCF7 breast cancer cells producing an anti-apoptotic effect. This study provides a working model for a mechanism by which estradiol promotes anti-apoptosis through membrane-associated ERα36, as seen in previous breast cancer models, suggesting that ERα36 may be a potential membrane target for drug design against breast cancer and laryngeal cancer.

miRNAs are short 18-22 base pair non coding RNAs that have been implicated as powerful modulators of a variety of cell processes, including proliferation, differentiation, and disease. However, these small molecule RNAs lack therapeutic translatability due to difficulties in delivery, including an inability to easily cross cell membranes and susceptibility to opsonization. This project seeks to design a delivery system using an in-situ gelling Cu++-free click hydrogel in combination with lipid nanoparticles (LNPs) as a means of locally delivering therapeutic small RNA molecules to treat various bone pathologies.

The role of matrix vesicles derived from osteoblast-lineage cells, including osteoblast- and osteocyte-like cells, in secondary bone formation and mature lamellar bone remains to be elucidated. As bone provides hydroxyapatite nucleation sites and mineralization of the ECM can occur by epitaxy, the role of matrix vesicles is most likely in cellular signaling. I am working to determine the enrichment of osteoblast-derived matrix vesicles, particularly regarding microRNA and proteins, then determining if these matrix vesicles can modulate osteogenesis via osteoblast differentiation with the ultimate aim to therapeutically utilize matrix vesicles to improve bone healing in a critical sized defect.