Research focuses on understanding how global programs of gene expression influence cell behavior and lineage, whether in normal developmental processes or in pathological states.
My group also operates a shared technology core for conducting transcriptomic and related analyses. Services and instrumentation provided by the core include DNA microarray analysis (Affymetrix), next-generation sequencing analysis (Ion Torrent), real-time PCR analysis (Bio-Rad Cffx96), and RNA quality analysis (Bioanalyzer 2100), together with bioinformatic support needed to apply these technologies.
Mechanisms controlling the production of elastin
Elastin is a connective tissue protein essential for the elastic qualities of numerous tissues, allowing them to regain their shape after stretching or contracting. Although the resilience of these tissues (including skin, blood vessels, lungs and cartilage) is essential for their function, elasticity declines with age and in response to injury and other environmental insults. This is due in part to accumulated damage in elastin fibers and the fact that elastin expression is limited (predominantly) to early development. Understanding how elastin expression is controlled would offer potential for various therapeutic treatments, for example, 1) re-initiating elastin production in conditions of elastin deficiency, and 2) controlling elastin production in tissue replacement constructs to ensure natural biomechanical properties. We are focused on understanding the transcriptional environment necessary for normal elastin synthesis. By mining several datasets, we have identified a group of genes coordinately expressed in elastin-producing systems. Current research is focused on understanding this putative elastogenic gene network using a biofabrication model of elastin synthesis that involves human endothelial cells and vascular smooth muscle cells co-cultured in macroporous gelatin beads.
Understanding the regenerative potential of the auditory system
Injury and/or degeneration of the auditory nerve leads to losses in hearing. This can occur as a function of aging or in response to noise or drug exposure. While hearing losses are generally viewed as permanent, recent studies have pointed to the existence of neural stem/progenitor cells (NSPCs), suggesting that these cells might be used to combat damage to the auditory system. In collaboration with Dr. Hainan Lang (MUSC, Department of Pathology), we are examining the potential for auditory regeneration in response to injury. Our studies highlight that NSPCs exist in the auditory nerve and that injury stimulates their proliferation and differentiation. Furthermore, transcriptional responses following injury evoke a process of de-differentiation, resembling normal development in reverse. Currently we are focusing on identifying the cells that convey neural/stem progenitor function, understanding the transcriptional mechanisms that control their response to injury, and investigating the blockages that limit the full repair of injuries.