Audrey McAlinden, PhD
My research focus is bone and cartilage – the two tissues that make up our skeleton. Specifically, we are interested in unraveling important mechanisms that regulate the development of these tissues. Understanding how osteogenesis and chondrogenesis are controlled at the cellular and molecular level provides us with critical information to devise novel strategies to treat bone and cartilage conditions such as non-healing bone fractures, heterotopic ossification (HO) and osteoarthritis (OA).
on epigenetic factors that regulate the differentiation of stem/progenitor cells toward the bone (osteoblast) or cartilage (chondrocyte) cell lineages. Epigenetic regulation is defined as mechanisms by which gene expression changes occur independent of alterations to the genetic code. Of these epigenetic factors, microRNAs (miRNAs) are a main focus. These are short non-coding RNAs that interact with specific sequences in target mRNAs resulting in suppression of protein synthesis. miRNAs can suppress translation of tens to hundreds of mRNAs within a given cell type, a feature that renders them as attractive therapeutic targets. Previous studies in our lab identified a miRNA expression signature during human long bone development. This work laid the foundation to pursue specific miRNA candidates that we predicted may have functional roles in regulating bone and cartilage development and homeostasis. We are currently pursuing two miRNA candidates that appear to regulate osteoblast and chondrocyte differentiation. We predict that these miRNAs function, in part, by modulating mitochondrial metabolism. Importantly, we have also shown that altering expression of these miRNA candidates can enhance bone fracture healing or inhibit abnormal heterotopic bone formation in clinically relevant mouse models of these conditions. We also find that these miRNA candidates affect cartilage development and, in collaboration with Dr. Farsh Guilak (enter his link here) we devising tissue engineering strategies with the goal of generating native-like osteochondral tissue. This work has translational importance within the context of osteoarthritis research and therapy. Please refer to the Projects link for more information.
long non-coding RNAs (lncRNAs). These epigenetic regulators function either in the nucleus or cytoplasm of the cell to affect gene expression. In another collaborative study with Dr. Farsh Guilak, we identified lncRNA candidates that appear to regulate chondrocyte differentiation. Current studies are geared toward deciphering how these lncRNA candidates affect chondrogenesis and if modulating their expression could be of use for purposes of cartilage tissue engineering or as a treatment to attenuate osteoarthritis.