Joshua Gasiorowski, Ph.D.

The tissue engineering and gene and cellular therapy technologies that comprise the broad field of regenerative medicine have held tremendous promise for decades, but they have not yet met expectations. The short list of clinicially approved gene therapy treatments are primarily ex vivo and there has been limited success creating clinically useful engineered tissues. Many of these technologies fail in the clinic because experimental therapies are often derived from in vitro models that lack the biochemical and biophysical signals that cells are exposed to in vivo. The work in my lab is focused on understanding and directing basic regenerative processes that occur when cells are exposed to synthetic extracellular matrix scaffolding materials and therapeutic transgenes.



Research projects

Project I
We are developing several different types of synthetic, natural and composite extracellular matrix scaffolds that support and direct cell growth for regenerative medicine purposes. By using an electrospinner, nano- and submicron scale synthetic fibers mats can be created. These substrates, with defined biophysical features, can influence specific cell behaviors, such as the directionally enhanced growth of nerve axons. We are also developing electrospinning techniques to fabricate nanofibers with hollow cores that house and release plasmid DNA upon exposure to active triggers. Finally, we are generating viable macroscale scaffolds by decellularizing inexpensive and abundant plant products and then reseeding them with mammalian cells. As these techniques are refined, they can be used as complementary strategies to treat a variety of diseases with a cell and gene therapy approach.




Project II
Cells are complex sensors that can detect and respond to a seemingly endless array of extracellular signals. While many of these signals are biochemical in nature, cell behaviors can also be modulated by biophysical cues. We employ several nano- and micro-scale engineering techniques, as mentioned above, to fabricate biomimetic substrates that allow us to characterize cell responses to biophysical cues in controlled, reproducible in vitro environments. Understanding these processes can help us elucidate basic science mechanisms in the fields of mechanotransduction, cell biology, development, and differentiation. We employ a variety of topographically patterned substrates to direct cell proliferation, migration, and gene expression for neuronal and endocrine based tissue engineering projects, as well as cancer diagnostic screens.




Project III
Non-viral transgene vectors are typically limited by short durations of expression. In order to successfully transfect and differentiate enough cells in vivo for tissue engineering and gene therapy purposes, we need to maximize gene delivery and transgene expression in adult stem cells. Part of the reason why non-viral plasmids have limited expression is that they fail to traffic to the nucleus, and then further into the appropriate subnuclear transcription centers. My laboratory is aimed at understanding the dynamic behavior of non-viral vectors inside of cells, specifically within the nucleus. We also study how extracellular biophysical cues influence intracellular plasmid movement in an attempt to modulate transgene expression for regenerative projects targeting neuronal and brown adipose tissues.