Tag: Parisa Hosseinzadeh

Design and Characterization of BMP-2 Protein Binders to Augment Non-Union Fracture Healing

Presenter(s): Karly Fear — Biology

Faculty Mentor(s): Parisa Hosseinzadeh

Session: (In-Person) Oral Panel—Daily Dose of Proteins

Each year, over 630,000 people in the US suffer from non-union bone fractures, or fractures that do not heal completely without further medical intervention. To improve bone healing in non-union fractures, researchers have shown that bone morphogenetic protein 2 (BMP-2) improves bone regeneration. However, it is critical to fine tune the physiological dose and spatiotemporal control of BMP-2 release from a delivery biomaterial to avoid adverse side effects such as abnormal bone growth. I leverage the structural and biophysical insight of molecular modeling and design to generate protein binders predicted to control the release of BMP-2 into a fracture site via affinity interactions. I characterize subsequent protein binder designs using yeast surface display and flow cytometry. Over 1,000 designs are tested using this high-throughput computational and experimental pipeline and I will further characterize the toxicity, stability, and structure of a subset of these designs for practical application.

Computational Design of Peptide Binders for Detection of MMP8, a Biomarker in Periodontal Disease

Presenter: Alonso Cruz — Human Physiology

Faculty Mentor(s): Parisa Hosseinzadeh

Session: (In-Person) Oral Panel—Healthy Considerations

Periodontal Disease affects roughly 50% of Americans age 30 and older. As it turns out, there is a striking pattern in the incidence of this disease. Studies in recent years have found the protein MMP8 to be an inflammatory biomarker in Periodontal Disease. Consequently, its detection can be helpful as a preventative tool in dentistry. While the idea of an MMP8-detecting biosensor has great potential for medical applications, selective detection of MMP8 is difficult due to its similarity to other MMP proteins at its active site. To conquer this hurdle, we take a novel approach, targeting surfaces on MMP8 that are distal from the active site. Using insights from structural comparisons between MMP8 and other MMPs, we focused our efforts on the hemopexin domain, a region of MMP8 with minimal similarity to other MMPs. Modern advances in computational protein design allow us to design peptides in predefined structures that can bind to protein targets of interest, such as MMP8. We used these methods to produce a library of computationally-designed peptides. In the project’s current stage, we analyze and experimentally validate the peptides to determine the highest- performing binders to MMP8. Overall, this project presents a tremendous opportunity to combat periodontal disease, a condition that is reaching epidemic proportions. Additionally, this project provides a framework for future studies to build upon and further establish computational science’s role in the field of medicine.