Research Focus: Synthetic Nanoparticle Antibodies (SNAbs) for Immunomodulation of Tuberculosis.
Research opportunities for undergrads: undergraduate researchers can assist with nanoparticle synthesis, in vitro/in vivo experiments, flow cytometry, single-cell RNA sequencing, and data analysis.

Annually, 10 million new cases and 1.5 million deaths are attributed to Tuberculosis (TB) globally. Mycobacterium tuberculosis (Mtb) infection causes immune dysregulation that surpasses the host’s beneficial immunity, heightening TB disease progression and lethality. Immunosuppressive myeloid cells, termed myeloid-derived suppressor cells (MDSCs), accumulate in the lung after Mtb infection, causing immunosuppression during TB by decreasing proliferation and survival of effector T cells. Additionally, MDSCs release proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines in the lung during TB infection. MDSCs were first shown to suppress Natural Killer (NK) cell and T cell cytotoxic functions in cancer via these cytokines, negatively regulating the tumor microenvironment. Current therapies used to deplete MDSCs, ranging from chemotherapeutics to small molecule inhibitors and monoclonal antibodies, have difficulties specifically targeting MDSCs, leading to limited efficacy.
We have developed an efficacious alternative to these approaches with novel multivalent synthetic nanoparticle antibodies (SNAbs) that target and deplete both monocytic (M) and polymorphonuclear MDSCs (PMN-MDSCs) in a mouse triple-negative breast cancer model through antibody-like killing mechanisms. SNAbs are bifunctional Janus gold nanoparticles (AuNPs modified with cell-targeting ligands on one hemisphere and antibody-fragment crystallizable (Fc)- mimicking ligands on the other hemisphere). They pair MDSCs with effector cells such as macrophages or NK cells, triggering MDSC killing. However, the efficacy of SNAbs as an immunotherapy for MDSC depletion in an Mtb infection model has yet to be studied. We aim to develop and optimize MDSC-targeting SNAbs to restore immune homeostasis and provide a potential immunotherapeutic strategy for TB in collaboration with Dr. Jyothi Rengarajan at Emory University. This project combines the Roy lab’s immunoengineering and nanotherapeutics with the Rengarajan lab’s expertise in TB immunology and pathogenesis.