Mingnan Chen

Peptides, including polypeptides, perform versatile and important functions in life. So, it is not a surprise that many new biomaterials were invented using them as building blocks to mimic, refine, enhance, or inhibit their biological functions. Many of these materials are purposely developed as a means to intervene in some important yet abnormal processes in the human body that cause diseases. However, to safely and effectively use these materials in humans, they have to be proved biocompatible. One frequently raised biocompatibility question about peptide materials is whether they are immunogenic. If a peptide material is immunogenic, and its induced immune responses jeopardize its biological functions and the health of its host, its medical applications are doomed to failure.

We are interested in understanding the interplays between exogenous peptides and the host immune systems so that we can apply our understandings to re-engineer known peptide materials and to modulate their immunogenicity without negatively impacting their established functions and properties. We are currently using elastin-like polypeptide or ELP, a popular type of peptide material as our model to carry our studies. Through the studies, we have generated a variant from conventional ELP, namely immunotolerant elastin-like polypeptides (iTEPs). We also hope, through the studies, to answer some fundamental immunogenicity questions shared by peptide material research. One example of such questions is whether different presentations of the same peptide to the immune system result in different immune responses to the peptides? For example, would immune responses be the same to the identical peptide when they are exposed to the immune system as a single molecule or an aggregate?

The second research thrust of our lab concerns medical applications of iTEPs. We are particularly interested in devising iTEP-based nanocarriers for vaccines. Because the sequences and sizes of recombinant iTEPs can be precisely controlled using genetic engineering approaches, we will be able to generate nanocarriers with well-defined sizes, physicochemical properties, and targeting ligands, which allows us to thoroughly investigate factors that may affect the efficacy of vaccine carriers. On the application aspect, because of the broad utilization of vaccines, our iTEP carriers may find applications in treating and preventing a wide spectrum of diseases such as cancer, infection, neurodegeneration, and autoimmunity. The second application focus of iTEPs is to use them deliver small cancer chemotherapeutics. One ongoing project in our lab is to devise iTEP nanoparticles to deliver anti-metastasis drugs to metastasis-initiating cells (MICs) in tumors. Here, we hypothesize that the pinpoint property of iTEP nanocarriers is instrumental for us to control spatial and temporal distributions of the drugs inside tumor tissues so that the drugs may have a better access to MICs than free drugs, which hopefully leads to a better metastasis inhibition outcome.