Nick Tsihlis’s focus is on developing and evaluating therapies for patients with vascular disease, as well as understanding the molecular mechanisms underlying how these therapies work. Specifically, he has been working on describing the link between UbcH10, a protein that is required for proper cell cycle progression and cell proliferation, and nitric oxide (NO). Since UbcH10 degrades cell cycle proteins cyclin A and B, he hypothesized that knocking it down in vascular smooth muscle cells (VSMC) would stop their proliferation. He found that both NO and siRNA decreased levels of UbcH10 in VSMC. UbcH10 acts to mediate the effects of NO on cells and can be used to elicit these effects more specifically than NO, thus establishing the importance of UbcH10 as a therapeutic target.
Tsihlis is very interested in the way that nanomaterials can be synthesized to target or mimic biological systems, thus allowing for delivery of therapeutic compounds specifically to tissues of interest. His previous collaboration with materials scientists delivered NO in vivo to inhibit neointimal hyperplasia. He also collaborated with a materials science group to design a peptide amphiphile that will bind to sites of hemorrhage. He plans to build on these collaborations to deliver other therapeutic molecules, such as siRNA and thrombin, in vivo. These studies will enable design of a modular delivery vehicle that can be modified to deliver any number of small molecules to various tissues in a targeted fashion. As many materials scientists lack biological training, he sees himself acting as a bridge spanning the worlds of biology and nanotechnology to improve the outcomes of patients.