Research Focus: Synthetic Nanoparticle Antibodies (SNAbs) for Immunomodulation in Musculoskeletal Trauma.
Research opportunities for undergrads: Assist with SNAb synthesis (both the gold and silica-based formulation), in-vitro cell culture experiments and scRNA -seq data analysis.

Traumatic musculoskeletal injuries affect 58% of civilians and 88% of combat-wounded patients and are the primary cause of death for individuals below the age of 451. Recently, it has been identified that systemic immune dysregulation and immunosuppression (SIDIS) contribute to the poor success of intervention strategies in severe trauma1–3. The SIDIS microenvironment is comprised of elevated immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) and decreased immune effector cells, including macrophages and effector T-cells1,4,5. Although SIDIS is widely accepted as an important factor in hampering functional healing in patients with trauma, key systemic immune players that contribute to this immunosuppressive milieu are poorly understood. Current strategies for addressing SIDIS include targeting systemic cytokines and molecular mediators of the immune system1,3, which have failed to restore the immune homeostasis necessary to improve outcomes for trauma survivors. Therefore, effective immunomodulatory strategies targeting immune components that manifest SIDIS are required to improve functional regeneration.

We have developed novel bifunctional Janus synthetic nanoparticle antibodies (SNAbs) that target and deplete MDSCs through antibody-like killing mechanisms. SNAbs consist of a core of gold nanoparticles that have MDSC-targeting ligands on one domain and antibody-fragment crystallizable (Fc)- mimicking ligands on the other domain. They pair MDSCs with effector cells such as macrophages or NK cells, triggering MDSC killing. Currently, we are working to develop other formulations of SNAbs to optimize MDSC-targeting and depletion to restore immune homeostasis and augment functional bone regeneration. The project is in collaboration with Robert Guldberg’s lab at the University of Oregon.

Relevant Publications:

• Cheng, A., Vantucci, C. E., Krishnan, L., Ruehle, M. A., Kotanchek, T., Wood, L. B., … & Guldberg, R. E. (2021). Early systemic immune biomarkers predict bone regeneration after trauma. Proceedings of the National Academy of Sciences, 118(8), e2017889118.
  https://www.pnas.org/doi/10.1073/pnas.2017889118
• Vantucci, C. E., Guyer, T., Leguineche, K., Chatterjee, P., Lin, A., Nash, K. E., … & Guldberg, R. E. (2022). Systemic Immune Modulation Alters Local Bone Regeneration in a Delayed Treatment Composite Model of Non-Union Extremity Trauma. Frontiers in Surgery, 961.
  https://static.frontiersin.org/articles/10.3389/fsurg.2022.934773/full