Projects in the Champion lab generally apply protein engineering strategies to naturally occuring proteins in order to synthesize novel materials capable of specific interations with cells or other proteins. The overall goal is to reverse disease through interference with immune function, inflammatory pathways or promotion of healing mechanisms. We create materials for diseases, such as breast cancer and inflammatory bowel disease, and wound healing.

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Anti-Inflammatory Materials

The body’s inflammatory response is a critical step in the wound healing process, not only in preventing infection but also in providing some of the signals required for new tissue formation. However, severe and chronic wounds often exhibit a prolonged inflammatory period and deficient healing. There is evidence suggesting that control of inflammation during healing can improve outcomes. Chronic inflammation is also a critical problem in autoimmune diseases and can lead to tissue damage and loss of function. Proteins called cytokines are a critical component of inflammation and they direct cellular activities. We are designing materials capable of interfering with inflammatory signaling for applications in wound healing and inflammatory bowel disease.

Protein and Peptide Nanoparticles for Vaccines

Vaccines made from pathogen proteins are emerging as an alternative to traditional whole-pathogen vaccines. A few recombinantly-expressed, conserved viral proteins could direct the immune system to generate protective antibodies against many subtypes of viruses, providing a platform for a universal influenza vaccine. However, the poor immunogenicity of these conserved proteins means strong immune responses are rare, and a major challenge for vaccine design is how to safely enhance the body’s reaction to these proteins. By making nanoparticles from crosslinked antigen proteins, we are leveraging the immune system’s inflammatory reactions to particulate matter to boost the body’s immune responses to our antigens. The antigen protein is both an immunization target and a biodegradable, immunogenic delivery vehicle, in contrast to traditional particulate adjuvants such as alum. We are exploring how these protein nanoparticles can be engineered to trigger immune responses to conserved influenza proteins, in collaboration with Dr. Baozhong Wang at Georgia State University. Futhermore, there is more research being performeed in our lab to look at conserved protein or peptide portions of many pathogenic bacteria or viruses can be used to create potentially more potent and effective vaccines for a number of other diseases.

Self-assembled protein-inorganic supraparticles for enzyme immobilization

In both industry and therapeutic drug-delivery, soluble enzymes are subject to degradation or loss of activity due to fluctuations in temperature, pH, and concentration of other solutes. However, enzymes can perform chemical reactions in a greener fashion than typical chemical processes, and have the potential to serve as therapeutic agents. Enzymes fused to binding domains can immobilize onto self-assembled protein-inorganic supraparticles, improving their activity and stability over a variety of conditions. The modularity of the system opens the door to many avenues of application. Current areas of interest are to create an industrially applicable biocatalyst for the enzymatic synthesis of pharmaceutical precursors, as well as investigate the activity and biocompatibility of anti-inflammatory enzymes immobilized onto supraparticles as a therapeutic material.

Breast Cancer Therapeutics

Breast cancer cells undergo a variety of changes in important signaling pathways that lead to abnormal behavior such as excessive growth, inability to die, and metastasis to other areas of the body. Some of these changes have even been linked to drug resistance that develops in response to chemotherapy treatment. It is clear that there is a critical need to explore non-traditional routes of controlling these malignant cells. This presents an opportunity to engineer, not just new ways to deliver chemotherapeutics, but entirely new types of therapeutic materials. We are making materials inspired by signaling pathway control strategies seen in nature to reverse abnormal signaling and restore cancer cells' ability to die.